Biology of Blood and Marrow Transplantation via MedWorm.com

Biology of Blood and Marrow Transplantation — Tue, 16 Mar 2010 15:21:08 +0100

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Officers and Directors of ASBMT

Biology of Blood and Marrow Transplantation — Tue, 16 Mar 2010 15:21:08 +0100

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Editorial Board

Biology of Blood and Marrow Transplantation — Tue, 16 Mar 2010 15:21:08 +0100

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Masthead (Purpose and Scope)

Biology of Blood and Marrow Transplantation — Tue, 16 Mar 2010 15:21:08 +0100

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Erratum

Biology of Blood and Marrow Transplantation — Fri, 26 Feb 2010 00:00:00 +0100

In “Pulmonary, Gonadal, and Central Nervous System Status after Bone Marrow Transplantation for Sickle Cell Disease” (Walters et al., Biol Blood Marrow Transplant 2009:16:263–272) the following author was omitted: Ann Haight, MD, Emory University, Atlanta, GA. (Source: Biology of Blood and Marrow Transplantation)

Biology of Blood and Marrow Transplantation — Tue, 09 Feb 2010 14:28:34 +0100

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Officers and Directors of ASBMT

Biology of Blood and Marrow Transplantation — Tue, 09 Feb 2010 14:28:34 +0100

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Editorial Board

Biology of Blood and Marrow Transplantation — Tue, 09 Feb 2010 14:28:34 +0100

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Masthead (Purpose and Scope)

Biology of Blood and Marrow Transplantation — Tue, 09 Feb 2010 14:28:34 +0100

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Antifungal Management

Biology of Blood and Marrow Transplantation — Tue, 09 Feb 2010 14:28:34 +0100

A 48-year-old man developed right lower lobe pneumonia 14 days after a cord blood transplant for acute leukemia. He had been on antibiotics for persistent fever; neutrophil count was 0; blood cultures and bronchoscopy were negative but serum galactomannan was 0.92 (positive >0.5). He was diagnosed with Aspergillus pneumonia and treated with voriconazole. (Source: Biology of Blood and Marrow Transplantation)

Response to Letter from Demetrios S. Theodoropoulos, MD, DSc

Biology of Blood and Marrow Transplantation — Mon, 08 Feb 2010 00:00:00 +0100

We appreciate Dr. Theodoropoulos' letter and comments . Dr. Theodoropoulos points out that the rapid changes in medicine today in both personalized molecular medicine and the emerging field of regeneration medicine is creating a new landscape that may alter our projections for the need for an expanded hematopoietic stem cell transplantation (HCT) workforce over the next decade. He is correct that these numbers could ultimately be curbed somewhat from our projections that were made based on the changing demographics of the aging population of this country, the expanded indications, and as have been documented with the recent publication by the Healthcare Cost and Utilization Project, which demonstrated that bone marrow transplant was associated with the greatest percentage change and total ...

Biology of Blood and Marrow Transplantation — Mon, 01 Feb 2010 00:00:00 +0100

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Officers and Directors of ASBMT

Biology of Blood and Marrow Transplantation — Mon, 01 Feb 2010 00:00:00 +0100

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Editorial Board

Biology of Blood and Marrow Transplantation — Mon, 01 Feb 2010 00:00:00 +0100

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Masthead (Purpose and Scope)

Biology of Blood and Marrow Transplantation — Mon, 01 Feb 2010 00:00:00 +0100

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Falling Chimerism after Reduced Intensity Conditioning Transplantation

Biology of Blood and Marrow Transplantation — Mon, 01 Feb 2010 00:00:00 +0100

A 54-year-old man with acute myelogenous leukemia (AML) in second complete remission received a reduced-intensity conditioning (RIC) stem cell transplant using fludarabine and intravenous busulfan. The donor was an 8/8 HLA-A, -B, -C, and -DRB1 matched unrelated male. Graft-versus-host disease (GVHD) prophylaxis was antithymocyte globulin, tacrolimus, and methotrexate (MTX) 5 mg/m2 on days 1, 3, 6, and 11, with a plan to taper tacrolimus by 30% at day 60, 30% on day 120, and discontinue at 6 months after transplantation. His tacrolimus was tapered at day 60 as planned. (Source: Biology of Blood and Marrow Transplantation)

The Role of Cytotoxic Therapy with Hematopoietic Stem Cell Transplantation in the Treatment of Follicular Lymphoma: An Evidence-Based Review

Biology of Blood and Marrow Transplantation — Thu, 28 Jan 2010 00:00:00 +0100

Clinical research examining the role of hematopoietic stem cell transplantation (SCT) in the therapy of follicular non-Hodgkin lymphoma in adults is presented and critically evaluated in this systematic evidence-based review. Specific criteria were used for searching the published literature and for grading the quality and strength of the evidence and the strength of the treatment recommendations. Treatment recommendations reached unanimously by a panel of follicular lymphoma experts are: (1) autologous SCT is recommended as salvage therapy based on pre-rituximab data, with a significant improvement in overall survival (OS) and progression-free (PFS) survival; (2) autologous SCT is not recommended as first-line treatment for most patients because of no significant improvement in OS; (3) au...

Challenges in Hematopoietic Stem Cell Transplantation

Biology of Blood and Marrow Transplantation — Mon, 11 Jan 2010 00:00:00 +0100

The article by Gajewski et al. regarding projected shortages in physicians specialized in hematopoietic stem cell transplantation (HSCT) deals with issues of capital importance for the delivery of state-of-the-art medical care. The scope of HSCT keeps expanding, and will include a number of nonmalignant/nonhematologic disorders, as diverse (and yet as similar) as systemic lupus erythematosus and Crohn's disease. At the same time, the needs for traditional indications, such as thalassemia, are not being met. In the United States alone, up to 70,000 patients with sickle cell disease—only 1 of the current indications—could benefit from nonmyeloablative HSCT . The current rate of 18,000 procedures/year mentioned by the authors would prove a gross underestimate were HSCT to reach its full...

Biology of Blood and Marrow Transplantation — Fri, 01 Jan 2010 00:00:00 +0100

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Officers and Directors of ASBMT

Biology of Blood and Marrow Transplantation — Fri, 01 Jan 2010 00:00:00 +0100

(Source: Biology of Blood and Marrow Transplantation)

Editorial Board

Biology of Blood and Marrow Transplantation — Fri, 01 Jan 2010 00:00:00 +0100

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Masthead

Biology of Blood and Marrow Transplantation — Fri, 01 Jan 2010 00:00:00 +0100

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ASBMT News

Biology of Blood and Marrow Transplantation — Fri, 01 Jan 2010 00:00:00 +0100

Allogeneic stem cell transplants for myelodysplastic syndrome (MDS) would be consistently eligible for Medicare reimbursement if the federal government accepts a formal request that has been submitted by ASBMT and the National Marrow Donor Program (NMDP), together with 10 other organizations. (Source: Biology of Blood and Marrow Transplantation)

Expansion of NKG2A−LIR1− Natural Killer Cells in HLA-Matched, Killer Cell Immunoglobulin-Like Receptors/HLA-Ligand Mismatched Patients following Hematopoietic Cell Transplantation

Biology of Blood and Marrow Transplantation — Thu, 31 Dec 2009 00:00:00 +0100

The prognosis after hematopoietic cell transplantation (HCT) for the treatment of leukemia or lymphoma in humans is influenced by donor-derived natural killer (NK) cells, which enhance the graft-versus-leukemia (GVL) effect. Such alloreactive killer cells can be generated in vivo after HCT if the donor expresses killer cell immunoglobulin-like receptors (KIRs), such as KIR2DL1, KIR2DL2/3, or KIR3DL1, for which the recipient lacks HLA class I ligands. We studied effector cells from 22 KIR/HLA-ligand mismatched and 14 KIR/HLA-ligand matched, primarily HLA-matched patient-donor pairs after allogeneic HCT. A novel 8-color flow cytometry panel allowed us to characterize effector-cell populations without “broadly reactive” inhibitory receptors such as CD94/NKG2A or LIR1. The numbers of such ...

Chemokine Receptor CCR5 Mediates AlloImmune Responses in Graft-versus-Host Disease

Biology of Blood and Marrow Transplantation — Thu, 17 Dec 2009 00:00:00 +0100

Allogeneic bone marrow transplantation (BMT) is an effective therapy for hematologic malignancies. However graft-versus-host disease (GVHD) is a major limiting factor for a successful patient outcome. GVHD is a result of alloimmune responses of donor T lymphocytes attacking the recipient's cells and tissues. Chemokine receptor CCR5 plays a role in solid organ allograft rejection and mediates murine GVHD pathogenesis. Herein, we report that infiltrating lymphocytes in the skin of human acute GVHD (aGVHD) samples are predominantly CCR5+ T cells. In addition, we characterized the features of the CCR5 expression on alloreactive T lymphocytes. We found that the CCR5+ population exhibits the characteristics of the activated effector T cell phenotype. CCR5 expression is upregulated upon allogenic...

Erratum

Biology of Blood and Marrow Transplantation — Thu, 17 Dec 2009 00:00:00 +0100

In “Guidelines for Preventing Infectious Complications among Hematopoietic Cell Transplant Recipients: A Global Perspective” (Tomblyn et al., Biol Blood Marrow Transplant 2009:15:1143-1238) three of the authors' names should be correctly spelled as: Louis Kirchhoff, Clovis Arns da Cunha, and Michael J. Boeckh. (Source: Biology of Blood and Marrow Transplantation)

Allogeneic Stem Cell Transplantation for Myelofibrosis with Leukemic Transformation

Biology of Blood and Marrow Transplantation — Mon, 14 Dec 2009 00:00:00 +0100

Leukemic transformation (LT) from myelofibrosis has a very poor prognosis with the current treatment strategies. We hypothesized that allogeneic stem cell transplantation (ASCT) can improve outcomes for patients with LT, and reviewed 55 consecutive patients that were treated for myelofibrosis with ASCT at our institution. Fourteen patients (25%) were identified to have LT. Thirteen of these patients received induction chemotherapy and 6 achieved remission at the time of transplant. Conditioning regimen was melphalan (Mel)-based in 9 patients. All patients engrafted and achieved remission after transplant, whereas 4 subsequently relapsed. After a median follow-up of 31 months, 6 patients (49%) survived long term. Although limited by a small number of patients, this study suggests that patie...

Gain of 1q21 Is an Unfavorable Genetic Prognostic Factor for Multiple Myeloma Patients Treated with High-Dose Chemotherapy

Biology of Blood and Marrow Transplantation — Mon, 14 Dec 2009 00:00:00 +0100

The prognostic significance of 1q21 gain, del(13)(q14), del(17)(p13), t(4;14)(p16.3;q32), and t(11;14)(q13;q32) detected by interphase fluorescein in situ hybridization (FISH) was studied in a cohort of 91 patients with newly diagnosed multiple myeloma (MM). 1q21 gain was detected in 37 of 91 patients (40.7%). In comparison with patients lacking 1q21 gain, patients with 1q21 gain had significantly shorter progression-free survival (PFS) (14.9 versus 27.4 months; P = .044) and worse 4-year overall survival (OS) (40.1% versus 76.2% of patients; P = (Source: Biology of Blood and Marrow Transplantation)

Early Elevation of C-Reactive Protein Correlates with Severe Infection and Nonrelapse Mortality in Children Undergoing Allogeneic Stem Cell Transplantation

Biology of Blood and Marrow Transplantation — Mon, 14 Dec 2009 00:00:00 +0100

In this study, we evaluated whether early elevations of CRP were associated with various complications and nonrelapse mortality following HSCT in pediatric patients. Seventy pediatric patients had CRP levels drawn at regular time points during the first week following their transplants. Patients were followed for 100 days following transplant, and transplant-related complications were documented. Patients who subsequently developed severe infections had higher median CRP values than those without severe infections (median 8.03 mg/dL versus 1.64 mg/dL, P = .0008) as did those who suffered nonrelapse mortality compared with those who did not (12.6 mg/dL versus 2.44 mg/dL, P = .02). These findings suggest that elevated CRP values may be useful as a marker of individual pediatric patients wit...

Allogeneic Hematopoietic Cell Transplant for Prolymphocytic Leukemia

Biology of Blood and Marrow Transplantation — Thu, 03 Dec 2009 00:00:00 +0100

The poor prognosis of patients with prolymphocytic leukemia (PLL) has led some clinicians to recommend allogeneic hematopoietic cell transplant (HCT). However, the data to support this approach is limited to case-reports and small case series. We reviewed the database of the Center for International Blood and Marrow Transplant Research (CIBMTR) to determine outcomes after allotransplant for patients with PLL. We identified 47 patients with a median age of 54 years (range: 30-75 years). With a median follow-up of 13 months, progression-free survival (PFS) was 33% (95% confidence interval [CI] 20%-47%) at 1 year. The most common cause of death was relapse or progression in 49%. The cumulative incidence of treatment-related mortality (TRM) at 1-year posttransplant was 28%. The small patient p...

Improved Survival with Inhibitory Killer Immunoglobulin Receptor (KIR) Gene Mismatches and KIR Haplotype B Donors after Nonmyeloablative, HLA-Haploidentical Bone Marrow Transplantation

Biology of Blood and Marrow Transplantation — Thu, 03 Dec 2009 00:00:00 +0100

Natural killer (NK) cell alloreactivity, which may contribute to the graft-versus-leukemia (GVL) effect of allogeneic hematopoietic stem cell transplantation (HSCT), is influenced by the interaction of killer-cell immunoglobulin-like receptors (KIRs) on donor NK cells and their ligands, human leukocyte antigen (HLA) class I molecules on recipient antigen-presenting cells (APCs). Distinct models to predict NK cell alloreactivity differ in their incorporation of information from typing of recipient and donor KIR and HLA gene loci, which exist on different autosomes and are inherited independently as haplotypes. Individuals may differ in the inheritance of the 2 KIR haplotypes, A and B, or in the expression of individual KIR genes. Here, we examined the effect of KIR and HLA genotype, in both...

High-Dose Chemotherapy with Blood or Bone Marrow Transplants for Rhabdomyosarcoma

Biology of Blood and Marrow Transplantation — Thu, 03 Dec 2009 00:00:00 +0100

We describe outcomes of 62 subjects receiving autologous blood/bone marrow (BM) transplants for RMS between 1989 and 2003, and reported to the Center for International Blood and Marrow Transplantation Research (CIBMTR). Histologic subtype was confirmed by reviewing pathology reports. Treatment-related mortality (TRM), progression-free survival (PFS), and overall survival (OS) were evaluated. Overall, 73% of subjects were 5 cm, 63% had metastasis at diagnosis, 55% had unfavorable histologies, 92% had cancer responsive to chemotherapy pretransplant, and 67% were in first remission. The 1-year TRM was 5% (95% confidence interval [CI], 1%-12%) and the 5-year PFS and OS were 29% (95% CI, 18%-41%) and 32% (95% CI, 21%-44%), respectively. There was only a 4% relapse rate after the first year. The...

Hypertension in Long-Term Survivors of Pediatric Hematopoietic Cell Transplantation

Biology of Blood and Marrow Transplantation — Thu, 03 Dec 2009 00:00:00 +0100

A retrospective study was conducted to determine risk factors for the development of hypertension (HTN) and to describe the prevalence among long-term survivors of pediatric hematopoietic cell transplant (HCT). Records of 689 pediatric patients who survived 5 years or more after HCT, from 1969 to 2004, were reviewed for development of HTN. In children, HTN was defined as either a systolic or diastolic pressure ≥95th percentile according to age, sex, and height. In adults, HTN was defined as systolic pressures ≥140 mmHg and/or diastolic pressures ≥90 mmHg in nondiabetic adults and systolic pressures ≥130 and/or diastolic pressures ≥80 in diabetic adults. Multivariate Cox regression models were used to estimate the hazard ratio (HR) of risk factors associated with HTN. All patients...

Erratum

Biology of Blood and Marrow Transplantation — Thu, 03 Dec 2009 00:00:00 +0100

In “Blood Stem Cell Transplantation in Older Patients” (Murphy et al., Biol Blood Marrow Transplant 2010:15:1638–1639) the following author was omitted: Marcel R. M. van den Brink, MD, PhD, Memorial Sloan-Kettering Cancer Center, New York. (Source: Biology of Blood and Marrow Transplantation)

The Addition of 400 cGY Total Body Irradiation to a Regimen Incorporating Once-Daily Intravenous Busulfan, Fludarabine, and Antithymocyte Globulin Reduces Relapse Without Affecting Nonrelapse Mortality in Acute Myelogenous Leukemia

Biology of Blood and Marrow Transplantation — Mon, 30 Nov 2009 00:00:00 +0100

This study confirms the importance of regimen intensity in allogeneic HSCT for AML. The combination of daily i.v. Bu, Flu, 400 cGy TBI, and ATG provides a well-tolerated regimen with antileukemic activity in AML comparable to that of other, conventional myeloablative (MA) regimens. (Source: Biology of Blood and Marrow Transplantation)

Cord Blood Units with Low CD34+ Cell Viability Have a Low Probability of Engraftment after Double Unit Transplantation

Biology of Blood and Marrow Transplantation — Mon, 23 Nov 2009 00:00:00 +0100

Double unit cord blood (CB) transplantation (CBT) appears to augment engraftment despite only one unit engrafting in most patients. We hypothesized that superior unit quality, as measured by a higher percentage of viable cells postthaw, would determine the engrafting unit. Therefore, we prospectively analyzed 46 double-unit transplants postthaw using flow cytometry with modified gating that included all dead cells. Using a 75% threshold (mean viability minus 2 SD), 20% of units had low CD34+ cell viability, with viability varying according to the bank of origin. Further, in the 44 patients with single unit engraftment, CD34+ cell viability was higher in engrafting units (P=.0016). Although either unit engrafted if both had high CD34+ viability, units with (Source: Biology of Blood and Marr...

Poor Mobilization of Hematopoietic Stem Cells—Definitions, Incidence, Risk Factors, and Impact on Outcome of Autologous Transplantation

Biology of Blood and Marrow Transplantation — Wed, 18 Nov 2009 00:00:00 +0100

As more efficient agents for stem cell mobilization are being developed, there is an urgent need to define which patient population might benefit from these novel drugs. For a precise and prospective definition of “poor mobilization” (PM), we have analyzed the efficiency of mobilization in patients intended to receive autologous transplantation at our center in the past 6 years. Between January 2003, and December 2008, 840 patients with the following diagnoses were scheduled to undergo leukapheresis: multiple myeloma (MM, n = 602) and non-Hodgkin lymphoma (NHL, n= 238). Most patients mobilized readily: close to 85% of the patients had a level of 20/μL to >500/μL of CD34+ cells at the peak of stimulation. Of the 840 patients, 129 (15.3%) were considered to be PMs, defined as patients ...

Nonmyeloablative HLA-Haploidentical Bone Marrow Transplantation with High-Dose Posttransplantation Cyclophosphamide: Effect of HLA Disparity on Outcome

Biology of Blood and Marrow Transplantation — Wed, 18 Nov 2009 00:00:00 +0100

Although some reports have found an association between increasing HLA disparity between donor and recipient and fewer relapses after allogeneic blood or marrow transplantation (BMT), this potential benefit has been offset by more graft-versus-host disease (GVHD) and nonrelapse mortality (NRM). However, the type of GVHD prophylaxis might influence the balance between GVHD toxicity and relapse. The present study analyzed the impact of greater HLA disparity on outcomes of a specific platform for nonmyeloablative (NMA), HLA-haploidentical transplantation. A retrospective analysis was performed of 185 patients with hematologic malignancies enrolled in 3 similar trials of NMA, related donor, haploidentical BMT incorporating high-dose posttransplantation cyclophosphamide for GVHD prophylaxis. No...

Mycophenolate Pharmacokinetics and Association with Response to Acute Graft-versus-Host Disease Treatment from the Blood and Marrow Transplant Clinical Trials Network

Biology of Blood and Marrow Transplantation — Wed, 18 Nov 2009 00:00:00 +0100

There are limited data as to the effectiveness of mycophenolate mofetil (MMF) plus high-dose corticosteroids for the treatment of acute graft-versus-host disease (aGVHD), and even less data regarding the pharmacokinetic disposition and exposure–response relationship of MMF in individuals with GVHD. MMF pharmacokinetics were studied in a multicenter Blood and Marrow Transplant Clinical Trials Network randomized phase II trial evaluating the effectiveness of MMF as one of 4 agents added to corticosteroids as treatment of aGVHD. Thirty-two of the patients randomized to receive MMF underwent pharmacokinetic sampling in weeks 1 and 2 were studied. Mean age was 41 ± 13.6 years. Twenty one (65.6%), 5 (15.6%), 6 (18.8%) patients had a complete response (CR), partial response (PR) or lesser resp...

Efficacy of Bone Marrow-Derived Mesenchymal Stem Cells in the Treatment of Sclerodermatous Chronic Graft-versus-Host Disease: Clinical Report

Biology of Blood and Marrow Transplantation — Wed, 18 Nov 2009 00:00:00 +0100

The success of treatment for sclerodermatous chronic graft-versus-host disease (ScGVHD) remains disappointing. The immunomodulatory ability of bone marrow (BM)–derived mesenchymal stem cells (MSCs) shows promise in treating GVHD, especially given its previous success in treating patients with acute GVHD (aGVHD). The potential efficacy and safety issues for treating cGVHD, particularly ScGVHD, remain to be clarified, however. Here, we report 4 patients with ScGVHD who received MSCs expanded ex vivo from unrelated donors by intra-BM injection. After MSC infusion, the ratio of helper T lymphocyte (Th) 1 cells to Th2 cells was dramatically reversed, with an increase in Th1 and a decrease in Th2 achieving a new balance. Correspondingly, symptoms gradually improved in all 4 patients. During th...

Comparison of Two Pretransplant Predictive Models and a Flexible HCT-CI Using Different Cut off Points to Determine Low-, Intermediate-, and High-Risk Groups: The Flexible HCT-CI Is the Best Predictor of NRM and OS in a Population of Patients Undergoing allo-RIC

Biology of Blood and Marrow Transplantation — Mon, 16 Nov 2009 00:00:00 +0100

In conclusion, our single-center study suggests that the flexible HCT-CI is a good predictor of 2-year NRM and survival after an allo-RIC. (Source: Biology of Blood and Marrow Transplantation)

Race and Outcomes of Autologous Hematopoietic Cell Transplantation for Multiple Myeloma

Biology of Blood and Marrow Transplantation — Mon, 16 Nov 2009 00:00:00 +0100

Blacks are twice as likely to develop and die from multiple myeloma (MM), and are less likely to receive an autologous hematopoietic-cell transplant (AHCT) for MM compared to Whites. The influence of race on outcomes of AHCT for MM is not well described. We compared the probability of overall survival (OS), progression-free survival (PFS), disease progression, and nonrelapse mortality (NRM) among Black (N=303) and White (N=1892) recipients of AHCT for MM, who were reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) from 1995 to 2005. The Black cohort was more likely to be female, and had better Karnofsky performance scores, but lower hemoglobin and albumin levels at diagnosis. Black recipients were younger and more likely to be transplanted later in their...

Low-Dose Total Body Irradiation and Fludarabine Conditioning for HLA Class I-Mismatched Donor Stem Cell Transplantation and Immunologic Recovery in Patients with Hematologic Malignancies: A Multicenter Trial

Biology of Blood and Marrow Transplantation — Mon, 09 Nov 2009 00:00:00 +0100

HLA-mismatched grafts are a viable alternative source for patients without HLA-matched donors receiving ablative hematopoietic cell transplantation (HCT), although their use in reduced intensity conditioning (RIC) or nonmyeloablative (NMA) conditioning HCT has been not well established. Here, we extended HCT to recipients of HLA class I-mismatched grafts to investigate whether NMA conditioning can establish stable donor engraftment. Fifty-nine patients were conditioned with fludarabine (Flu) 90 mg/m2 and 2 Gy total body irradiation (TBI), followed by immunosuppression with cyclosporine (CsA) 5.0 mg/kg twice a day and mycophenolate mofetil (MMF) 15 mg/kg 3 times a day for transplantation of granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood stem cells (PBSCs) from rela...

Biology of Blood and Marrow Transplantation — Fri, 06 Nov 2009 14:22:39 +0100

(Source: Biology of Blood and Marrow Transplantation)

Officers and Directors of ASBMT

Biology of Blood and Marrow Transplantation — Fri, 06 Nov 2009 14:22:39 +0100

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Editorial Board

Biology of Blood and Marrow Transplantation — Fri, 06 Nov 2009 14:22:39 +0100

(Source: Biology of Blood and Marrow Transplantation)

Masthead

Biology of Blood and Marrow Transplantation — Fri, 06 Nov 2009 14:22:39 +0100

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ASBMT News

Biology of Blood and Marrow Transplantation — Fri, 06 Nov 2009 14:22:39 +0100

Allogeneic stem cell transplants for myelodysplastic syndrome (MDS) would be consistently eligible for Medicare and Medicaid reimbursement if the federal government accepts a formal request that has been submitted by ASBMT and the National Marrow Donor Program (NMDP), together with 10 other organizations. (Source: Biology of Blood and Marrow Transplantation)

Blood Stem Cell Transplantation in Older Patients

Biology of Blood and Marrow Transplantation — Fri, 06 Nov 2009 14:22:39 +0100

This report recommends research priorities that can help close the gaps in our understanding of aging as it relates to HSCT and cancer. (Source: Biology of Blood and Marrow Transplantation)

Reduced Frequency of Regulatory T Cells in Peripheral Blood Stem Cell Compared to Bone Marrow Transplantations

Biology of Blood and Marrow Transplantation — Mon, 02 Nov 2009 00:00:00 +0100

We report herein that Treg frequencies are significantly reduced in PBSC compared to BM transplants. Furthermore, most Tregs from PBSC transplants are CD62Llo, a phenotype reported to have poor suppressor activity. Both granulocyte-colony stimulating factor (G-CSF) administration and leukapheresis were found to contribute to the loss of CD62L+ Tregs. Although higher T cell numbers are infused in PBSCT than in BMT, it is possible that the reduced Treg content of PBSC transplants may represent 1 factor contributing to the higher risk of GVHD reported after PBSCT. (Source: Biology of Blood and Marrow Transplantation)

New-Onset Lymphopenia Assessed during Routine Follow-up Is a Risk Factor for Relapse Postautologous Peripheral Blood Hematopoietic Stem Cell Transplantation in Patients with Diffuse Large B-Cell Lymphoma

Biology of Blood and Marrow Transplantation — Mon, 02 Nov 2009 00:00:00 +0100

A specific predictor during routine follow-up to ascertain risk for postautologous peripheral blood hematopoietic stem cell transplantation (post-APHSCT) relapse in non-Hodgkin lymphoma (NHL) has not been identified. Thus, we studied if new-onset lymphopenia measured by the absolute lymphocyte count (ALC) was a marker of post-APHSCT NHL relapse. ALC was obtained at the time of confirmed relapse, and at last follow-up with no relapse. From 1993 until 2005, 269 patients treated with APHSCT for diffuse large B-cell lymphoma (DLBCL) were included in this study. Patients at last follow-up without relapse (N=137) had a higher ALC compared with those with low ALC at the time of confirmed relapsed (N=132) (median ALC ×109/L of 1.66 versus 0.71, P < .0001, respectively). ALC at follow-up was a str...

Outcomes of Hematologic Malignancies after Unrelated Donor Hematopoietic Cell Transplantation According to Place of Residence

Biology of Blood and Marrow Transplantation — Mon, 02 Nov 2009 00:00:00 +0100

Studies suggest that patients who live in rural areas may have worse clinical outcomes compared with patients living in urban areas. We studied whether place of residence (rural versus urban) is associated with clinical outcomes of patients with leukemia or myelodysplastic syndrome (MDS) who received an unrelated donor hematopoietic cell transplantation (HCT). Patients' residential ZIP code at the time of transplant was used to determine rural or urban designation based on the Rural Urban Commuting Codes. The study included 6140 patients reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) from 121 U.S. HCT centers: 1179 (19%) came from rural areas, whereas 4961 (81%) came from urban areas. Rural and urban patients were similar in patient-, disease-, and t...

Outcome of Transplantation for Myelofibrosis

Biology of Blood and Marrow Transplantation — Mon, 02 Nov 2009 00:00:00 +0100

In this study, we analyze the outcomes of 289 patients receiving allogeneic transplantation for primary myelofibrosis between 1989 and 2002, from the database of the Center for International Bone Marrow Transplant Research (CIBMTR). The median age was 47 years (range: 18-73 years). Donors were HLA identical siblings in 162 patients, unrelated individuals in 101 patients, and HLA nonidentical family members in 26 patients. Patients were treated with a variety of conditioning regimens and graft-versus-host disease (GVHD) prophylaxis regimens. Splenectomy was performed in 65 patients prior to transplantation. The 100-day treatment-related mortality was 18% for HLA identical sibling transplants, 35% for unrelated transplants, and 19% for transplants from alternative related donors. Correspondi...

Rapid, Flow Cytometric Assay for NK Alloreactivity Reveals Exceptions to Rules Governing Alloreactivity

Biology of Blood and Marrow Transplantation — Mon, 02 Nov 2009 00:00:00 +0100

Alloreactive NK cells lyse target cells lacking self-HLA-C or the HLA-B-Bw4 epitope. Prior to haploidentical stem cell transplants, donor alloreactivity toward the patient is evaluated by natural killer (NK) cloning followed by testing of the clones in the 51Cr-release assay. As only a few percent of NK clones are alloreactive, a large number of NK clones must be established and evaluated. This approach is laborious and time consuming, with a complete evaluation taking up to 6 weeks. We developed a flow cytometry-based cytotoxicity assay utilizing CD107a expression on 12-day polyclonally expanded NK cells and showed that NK alloreactivity mediated by inhibitory and activating KIR can be detected by measuring CD107a expression following incubation with targets lacking the appropriate class ...

Pre-Engraftment Syndrome after Double-Unit Cord Blood Transplantation: A Distinct Syndrome not Associated with Acute Graft-Versus-Host Disease

Biology of Blood and Marrow Transplantation — Mon, 26 Oct 2009 00:00:00 +0100

Pre-engraftment syndrome (PES) occurring after cord blood transplantation (CBT) is poorly characterized. We reviewed 52 consecutive double-unit CBT recipients treated for high-risk hematologic malignancies. PES was defined as unexplained fever >38.3°C (101°F) not associated with infection and unresponsive to antimicrobials, and/or unexplained rash occurring before or at neutrophil recovery. CBT recipients (median age, 38 years; range, 3-66 years) received either myeloablative (MA; n=36) or nonmyeloablative (NMA; n=16) conditioning. Sixteen patients (31%) fulfilled PES criteria: 15 with fever (median at onset, 39°C [102.2°F]), 13 of whom also had rash, and 1 with rash alone. The median onset was 9 days (range, 5-12 days) posttransplantation (a median of 14 days before neutrophil recover...

The Role of Missing Killer Cell Immunoglobulin-Like Receptor Ligands in T Cell Replete Peripheral Blood Stem Cell Transplantation from HLA-Identical Siblings

Biology of Blood and Marrow Transplantation — Mon, 26 Oct 2009 00:00:00 +0100

The contribution of natural killer (NK) cells to graft-versus-malignancy (GVM) effects following hematopoietic stem cell transplantation (HSCT) remains uncertain, particularly in the HLA-identical setting. A model considering missing HLA ligands to the donor's inhibitory killer cell immunoglobulin-like receptor (KIR), termed the missing KIR ligand model, has been established in T cell depleted bone marrow transplantation (BMT), but lacks validity in other cohorts with different treatment characteristics. We hypothesized that the impact of missing KIR ligands on relapse-free survival (RFS) and overall survival (OS) in T cell replete peripheral blood SCT (PBSCT) differs from that in the T cell depleted BMT setting, and retrospectively evaluated 100 consecutive, HLA-identical sibling transpla...

Robert Truitt Tribute

Biology of Blood and Marrow Transplantation — Fri, 16 Oct 2009 00:00:00 +0100

It is with great pleasure that we are able to pay tribute to Robert Truitt, PhD, for his many contributions to the field of hematopoietic stem cell transplantation. Bob will be stepping down at the end of this year from a career in experimental allogeneic bone marrow transplantation that spans more than three decades. He is recognized as one of the pioneers in the use of experimental mouse models to separate GVL from GVHD, and his work has provided many important contributions towards understanding the cellular nature of the GVL effect. (Source: Biology of Blood and Marrow Transplantation)

Successful Hematopoietic Stem Cell Transplantation in 2 Children with X-Linked Chronic Granulomatous Disease from Their Unaffected HLA-Identical Siblings Selected Using Preimplantation Genetic Diagnosis Combined with HLA Typing

Biology of Blood and Marrow Transplantation — Thu, 15 Oct 2009 00:00:00 +0100

This report demonstrates that HSCT with HLA-matched sibling donors created by PGD/HLA typing of in vitro fertilized embryos is a realistic therapeutic option and should be presented as such to families with children who require a non-urgent HSCT but lack an HLA-genoidentical donor. (Source: Biology of Blood and Marrow Transplantation)

An Age-Dependent Pharmacokinetic Study of Intravenous and Oral Mycophenolate Mofetil in Combination with Tacrolimus for GVHD Prophylaxis in Pediatric Allogeneic Stem Cell Transplantation Recipients

Biology of Blood and Marrow Transplantation — Thu, 15 Oct 2009 00:00:00 +0100

Acute graft-versus-host disease (aGVHD) still remains a major limiting factor following allogeneic stem cell transplantation (AlloSCT) in pediatric recipients. Mycophenolate mofetil (MMF), an uncompetitive selective inhibitor of inosine monophosphate dehydrogenase, is a new immunosuppressant agent without major mucosal, hepatic, or renal toxicity compared to other prophylactic aGVHD immunosuppressant drugs. Although there has been an extensive pharmacokinetic (PK) experience with MMF administration following solid organ transplantation in children, there is a paucity of PK data following its use in pediatric AlloSCT recipients. We investigated the safety and PK of MMF as GVHD prophylaxis following intravenous (i.v.) and oral (p.o.) administration (900 mg/m2 every 6 hours) in conjunction wi...

Partial T Cell-Depleted Allogeneic Stem Cell Transplantation following Reduced-Intensity Conditioning Creates a Platform for Immunotherapy with Donor Lymphocyte Infusion and Recipient Dendritic Cell Vaccination in Multiple Myeloma

Biology of Blood and Marrow Transplantation — Thu, 15 Oct 2009 00:00:00 +0100

This study demonstrates that transplantation with a partial T cell-depleted graft creates a platform for boosting GVM immunity by preemptive donor lymphocyte infusion (DLI) and recipient dendritic cell (DC) vaccination, with limited GVHD. All 20MM patients engrafted successfully. Chimerism analysis in 19 patients evaluable at 3 months revealed that 7 patients were complete donor, whereas 12 patients were mixed chimeric. Grade II acute GVHD (aGVHD) occurred in 7 patients (35%) and only 4 patients (21%) developed chronic GVHD (cGVHD). Fourteen patients received posttransplantation immunotherapy, 8 preemptive DLI, 5 patients both DLI and DC vaccination, and 1 patient DC vaccination only. DC vaccination was associated with limited toxicity, and none of these patients developed GVHD. Importan...

Monitoring and Preemptive Rituximab Therapy for Epstein-Barr Virus Reactivation after Antithymocyte Globulin Containing Nonmyeloablative Conditioning for Umbilical Cord Blood Transplantation

Biology of Blood and Marrow Transplantation — Thu, 15 Oct 2009 00:00:00 +0100

Epstein Barr viremia (EBV) and posttransplantation lymphoproliferative disorder (PTLD) are complications of hematopoietic stem cell transplantation (HSCT). The use of antithymocyte globulin (ATG) in recipients of umbilical cord HSCT is a known risk factor for the development of PTLD. In this high-risk population, we implemented an EBV monitoring program with preemptive therapy with rituximab (375mg/m2 intravenously [i.v.]) for EBV viremia (>1000 copies/mL). Eight of 35 patients treated with a UCB HSCT between 2007 and 2009, developed EBV viremia. Two of 7 developed PTLD (with 1 of the 2 dying of PTLD), despite prophylactic rituximab use. When compared with our previously described cohort where 6 of 30 developed EBV viremia and 5 of 6 patients developed PTLD (with 2 of 5 dying of PTLD), the...

Biology of Blood and Marrow Transplantation — Tue, 13 Oct 2009 13:25:11 +0100

(Source: Biology of Blood and Marrow Transplantation)

Officers and Directors of ASBMT

Biology of Blood and Marrow Transplantation — Tue, 13 Oct 2009 13:25:11 +0100

(Source: Biology of Blood and Marrow Transplantation)

Editorial Board

Biology of Blood and Marrow Transplantation — Tue, 13 Oct 2009 13:25:11 +0100

(Source: Biology of Blood and Marrow Transplantation)

Masthead

Biology of Blood and Marrow Transplantation — Tue, 13 Oct 2009 13:25:11 +0100

(Source: Biology of Blood and Marrow Transplantation)

Minor ABO-Mismatches are Risk Factors for Acute Graft-versus-Host Disease in Hematopoietic Stem Cell Transplant Patients

Biology of Blood and Marrow Transplantation — Tue, 13 Oct 2009 13:25:09 +0100

We investigated the impact of ABO and Rhesus (Rh) blood group matching on the outcome of hematopoietic stem cell transplantation (HSCT) of 154 patients matched at 10/10 HLA loci with unrelated donors. ABO and Rh, as potential risk factors, were modeled with the clinical outcome—acute and chronic graft-versus-host disease (aGVHD, cGVHD), relapse, treatment-related mortality (TRM), and overall survival (OS)—by simple, multiple, and competing risk analyses. We found that minor ABO-mismatches represent a significant risk factor for aGVHD (II-IV) with an estimated risk increase of almost 3-fold (hazard ratio [HR]=2.92, 95% confidence interval [CI]: 1.43-5.95, P=.003), and even 4-fold for aGVHD (III-IV) (HR=4.24, 95% CI: 1.70-10.56, P=.002), but not for other transplant endpoints. No signifi...

Pulmonary, Gonadal, and Central Nervous System Status after Bone Marrow Transplantation for Sickle Cell Disease

Biology of Blood and Marrow Transplantation — Mon, 12 Oct 2009 00:00:00 +0100

We conducted a prospective, multicenter investigation of human-leukocyte antigen (HLA) identical sibling bone marrow transplantation (BMT) in children with severe sickle cell disease (SCD) between 1991 and 2000. To determine if children were protected from complications of SCD after successful BMT, we extended our initial study of BMT for SCD to conduct assessments of the central nervous system (CNS) and of pulmonary function 2 or more years after transplantation. In addition, the impact on gonadal function was studied. After BMT, patients with stroke who had stable engraftment of donor cells experienced no subsequent stroke events after BMT, and brain magnetic resonance imaging (MRI) exams demonstrated stable or improved appearance. However, 2 patients with graft rejection had a second st...

The Effect of the Composition of Unrelated Donor Bone Marrow and Peripheral Blood Progenitor Cell Grafts on Transplantation Outcomes

Biology of Blood and Marrow Transplantation — Mon, 12 Oct 2009 00:00:00 +0100

To test the hypothesis that the outcome of hematopoietic stem cell (HSC) grafts is at least partially determined by the cellular composition of the graft, the National Marrow Donor Program (NMDP) analyzed the correlation of cellular phenotypes of unrelated grafts with graft outcome. Samples from 94 bone marrow (BM) and 181 peripheral blood progenitor cell (PBPC) grafts for transplantations at 40 U.S. transplant centers between 2003 and 2005 were analyzed at a single immunophenotyping reference laboratory. Samples were shipped from transplant centers upon receipt of graft. Graft cellular composition included analysis of leukocyte total cell numbers, and subsets of myeloid [CD34+, CD34+ CD38−], lymphoid [CD3+, CD3+ CD4+, CD3+ CD8+], and activated lymphoid cells [CD3+ CD25+, CD3+ CD69+, CD3...

Association of HMGB1 Polymorphisms with Outcome after Allogeneic Hematopoietic Cell Transplantation

Biology of Blood and Marrow Transplantation — Mon, 12 Oct 2009 00:00:00 +0100

Several studies have demonstrated that genetic variation in cytokine genes can modulate the immune reactions after allogeneic hematopoietic cell transplantation (HCT). High mobility group box 1 protein (HMBG1) is a pleiotropic cytokine that functions as a pro-inflammatory signal, important for the activation of antigen presenting cells (APCs) and propagation of inflammation. HMGB1 is implicated in the pathophysiology of a variety of inflammatory diseases, and we have recently found the variation in the HMGB1 gene to be associated with mortality in patients with systemic inflammatory response syndrome. To assess the impact of the genetic variation in HMGB1 on outcome after allogeneic HCT, we genotyped 276 and 146 patient/donor pairs treated with allogeneic HCT for hematologic malignancies f...

Hepatic Veno-Occlusive Disease following Stem Cell Transplantation: Incidence, Clinical Course, and Outcome

Biology of Blood and Marrow Transplantation — Fri, 09 Oct 2009 00:00:00 +0100

The occurrence of hepatic veno-occlusive disease (VOD) has been reported in up to 60% of patients following stem cell transplantation (SCT), with incidence varying widely between studies depending on the type of transplant, conditioning regimen, and criteria used to make the diagnosis. Severe VOD is characterized by high mortality and progression to multiorgan failure (MOF); however, there is no consensus on how to evaluate severity. This review and analysis of published reports attempts to clarify these issues by calculating the overall mean incidence of VOD and mortality from severe VOD, examining the effect of changes in SCT practice on the incidence of VOD over time, and discussing the methods used to evaluate severity. Across 135 studies performed between 1979 and October 2007, the ov...

Erratum

Biology of Blood and Marrow Transplantation — Thu, 08 Oct 2009 00:00:00 +0100

In the article entitled “Successful treatment of severe acute intestinal graft versus host resistant to systemic and topical steroids with alemtuzumab” by Finke et al., in the August 2009 issue of Biology of Blood and Marrow Transplantation (Volume 15, Number 8, pages 910-918), M Schnitzler and J Hasskarl equally contributed to the manuscript. (Source: Biology of Blood and Marrow Transplantation)

Iron Overload in Patients Receiving Allogeneic Hematopoietic Stem Cell Transplantation: Quantification of Iron Burden by a Superconducting Quantum Interference Device (SQUID) and Therapeutic Effectiveness of Phlebotomy

Biology of Blood and Marrow Transplantation — Thu, 08 Oct 2009 00:00:00 +0100

Iron overload (IO) is a known adverse prognostic factor in patients who undergo allogeneic hematopoietic stem cell transplantation (HSCT) for thalassemia and appears to play a similar role in patients with other hematologic disorders. The estimation of IO is based primarily on serum ferritin level; however, many confounding factors can result in ferritin overestimation, especially in HSCT recipients. The aim of the present study was to quantify IO after HSCT using a superconducting quantum interference device (SQUID), and to evaluate the impact of IO on hepatic function and infections. In addition, the feasibility of iron depletion was investigated. A total of 102 consecutive allogeneic HSCT recipients admitted to our outpatient department between December 2005, and December 2007, were ana...

Outcome of 125 Children with Chronic Myelogenous Leukemia Who Received Transplants from Unrelated Donors: The Japan Marrow Donor Program

Biology of Blood and Marrow Transplantation — Mon, 05 Oct 2009 00:00:00 +0100

Because of a small number of patients, only a few studies have addressed the outcome of bone marrow transplantation (BMT) in children with Philadelphia chromosome–positive (Ph+) chronic myelogenous leukemia (CML), who receive graft from a volunteer-unrelated donor (VUD), especially after practical application of imatinib mesylate. The outcomes of BMT from a VUD in 125 children with Ph+ CML were retrospectively reviewed. Patients were identified through the Japan Marrow Donor Program as having undergone BMT between 1993 and 2005 and were aged 1-19 years at the time of transplant (median age, 14 years). The probabilities of 5-year overall survival (OS) and leukemia-free survival (LFS) were 59.3% and 55.5%, respectively. Multivariate analysis identified the following unfavorable survival fa...

T helper17 Cells Are Sufficient But Not Necessary to Induce Acute Graft-Versus-Host Disease

Biology of Blood and Marrow Transplantation — Mon, 05 Oct 2009 00:00:00 +0100

T helper (Th)1 cells were considered responsible for the induction of graft-versus-host disease (GVHD), but recently the concept has been challenged. Th17 cells play a critical role in mediating autoimmune diseases, but their role in the pathogenesis of GVHD remains unclear. Herein we compare the ability of in vitro generated Th1 and Th17 cells from C57BL/6 mice to induce GVHD in lethally irradiated BALB/c recipients. Allogeneic Th17 cells had superior expansion and infiltration capabilities in GVHD target organs, which correlated with their increased pathogenicity when compared with naïve or Th1 controls. Th17 cells caused no pathology in the syngeneic recipients, indicating that antigen-activation was required for their pathogenicity. Polarized Th17 cells could not maintain their phenot...

Critical Situation of Bone Marrow Transplantation: Information Distribution Regarding the Problem of a Shortage of Bone Marrow Filters

Biology of Blood and Marrow Transplantation — Mon, 05 Oct 2009 00:00:00 +0100

Many drugs and devices are essential to conduct hematopoietic stem cell transplantation (HSCT). The hematopoietic transplant community has been influenced by numerous drug and device shortages over the past several years in both Japan and other countries. This problem has included critical drugs for hematopoietic transplantations such as gancycrlovir, dexamethasone, lenograstim, imipenam, and cephepime. Recently, the discontinuation in the supply of the anticancer drug thio-tepa was announced by a pharmaceutical company in Japan; however, this process and decision were not sufficiently disclosed by the Ministry of Health, Labor, and Welfare (MHLW). As a result, the hematopoietic transplant communities are thus considered to urgently require the establishment of effective management in the ...

Interleukin 17 Is Not Required for Autoimmune-Mediated Pathologic Damage during Chronic Graft-versus-Host Disease

Biology of Blood and Marrow Transplantation — Mon, 05 Oct 2009 00:00:00 +0100

In this study, we demonstrate using a combination of antibody-based and genetic approaches that IL-17 is not required for the loss of self-tolerance and resulting CD4+T cell-dependent pathologic damage that occurs during the evolution from aGVHD to cGVHD. Rather, TH1 cells and other proinflammatory cytokines are fully competent to promote autoimmune-mediated tissue damage. Thus, the selective targeting of IL-17 may not be a viable clinical strategy for preventing the autoimmune manifestations that develop during cGVHD. (Source: Biology of Blood and Marrow Transplantation)

Oral Chronic Graft-versus-Host Disease Scoring Using the NIH Consensus Criteria

Biology of Blood and Marrow Transplantation — Mon, 05 Oct 2009 00:00:00 +0100

The objective of this study was to assess inter- and intraobserver variability in the component and composite scores in patients evaluated with oral cGVHD. Twenty-four clinicians (bone marrow transplant [BMT] oncologists: BMTE, n = 16; BMT midlevel providers: BMT MLP; n = 4; and oral medicine experts [OME], n = 4), from 6 major transplant centers scored high-quality intraoral photographs of 12 patients. The same photographs were evaluated 1 week later by the same evaluators. An intraclass correlation coefficient (ICC) was used to calculate intrarater reliability and interrater agreement was analyzed using a weighted κ statistic: 0 ≤ κ ≤ 0.20 = poor, 0.21 ≤ κ ≤ 0.40 = fair, 0.41 ≤ κ ≤ 0.60 = moderate, 0.61 ≤ κ ≤ 0.80 = good, 0.81 ≤ κ ≤ 1.00 = very good. Data on pa...

Transplantation of Unrelated Donor Umbilical Cord Blood for Nonmalignant Diseases: a Single Institution's Experience with 45 Patients

Biology of Blood and Marrow Transplantation — Mon, 05 Oct 2009 00:00:00 +0100

The potential benefits of unrelated donor bone marrow transplantation are offset by the immunologic complications of graft-versus-host disease (GVHD) and infection. We used cryopreserved umbilical cord blood (UCB) as a strategy to reduce the risks of GVHD and treatment-related mortality (TRM) and improved survival. Data on 45 patients with median age of 4.5 years who received transplants between October 2003 and February 2009 for the treatment of nonmalignant diseases were evaluated. As of May 15, 2009, the median follow-up was 25 months (range: 3-66). The majority (82%) of patients received an HLA-mismatched graft. The median infused total nucleated cell dose was 7.6×107/kg and CD34+ count 4.0×105/kg. Primary graft failure was encountered after 4 transplantations (8%). Log-rank tests an...

Hematopoietic Stem Cell Transplantation for Refractory or Recurrent Non-Hodgkin Lymphoma in Children and Adolescents

Biology of Blood and Marrow Transplantation — Thu, 01 Oct 2009 00:00:00 +0100

We examined the role of hematopoietic stem cell transplantation (HSCT) for patients aged≤18 years with refractory or recurrent Burkitt (n=41), lymphoblastic (n=53), diffuse large B cell (DLBCL; n=52), and anaplastic large cell lymphoma (n=36), receiving autologous (n=90) or allogeneic (n=92; 43 matched sibling and 49 unrelated donor) HSCT in 1990-2005. Risk factors affecting event-free survival (EFS) were evaluated using stratified Cox regression. Characteristics of allogeneic and autologous HSCT recipients were similar. Allogeneic donor HSCT was more likely to use irradiation-containing conditioning regimens, bone marrow (BM) stem cells, be performed in more recent years, and for lymphoblastic lymphoma. EFS rates were lower for patients not in complete remission at HSCT, regardless of d...

High-Dose Chemotherapy with Autotransplantation in AL Amyloidosis: A Flawed Meta-analysis

Biology of Blood and Marrow Transplantation — Thu, 01 Oct 2009 00:00:00 +0100

The conclusions of the meta-analysis by Mhaskar et al. evaluating high-dose chemotherapy with autotransplantation in immunoglobulin light chain amyloidosis are compromised by the omission of a key publication and flawed analytical techniques. The meta-analysis included 1 prospective randomized study of 100 patients and 2 nonrandomized studies containing a total of 49 patients. The pooled results of these 3 studies showed superior overall survival (OS) with conventional chemotherapy (CC) compared to autologous hematopoietic stem cell transplantation (AHSCT) (hazard ratio 1.79; P=.018). (Source: Biology of Blood and Marrow Transplantation)

2009 Research Priorities

Biology of Blood and Marrow Transplantation — Wed, 30 Sep 2009 23:00:00 +0100

The American Society for Blood and Marrow Transplantation has reviewed recent advances and problems in hematopoietic cell transplantation (HCT), and has identified priorities in several areas of basic and clinical research: (Source: Biology of Blood and Marrow Transplantation)

Response: Re: High-Dose Chemotherapy with Autotransplantation in AL Amyloidosis: A Flawed Meta-analysis

Biology of Blood and Marrow Transplantation — Mon, 28 Sep 2009 00:00:00 +0100

The primary claim put forward by Dr. Mehta et al. is that there is “reliable” evidence that autologous stem cell transplantation is superior to conventional chemotherapy. Any reasonable observer would conclude with the main findings of our systematic review that there is a paucity of reliable data on the efficacy of autologous stem cell transplantation in AL amyloidosis, and this is precisely the conclusion of our manuscript . (Source: Biology of Blood and Marrow Transplantation)

Improved Outcomes Using Tacrolimus/Sirolimus for Graft-versus-Host Disease Prophylaxis with a Reduced-Intensity Conditioning Regimen for Allogeneic Hematopoietic Cell Transplant as treatment of Myelofibrosis

Biology of Blood and Marrow Transplantation — Sun, 27 Sep 2009 00:00:00 +0100

In this report, we present results for 23 consecutive patients, including extended follow up for 9 patients previously reported who received cyclosporine (CsA)/mycophenolate moffetil (MMF)±MTX, and the current series of 14 patients who received tacrolimus/sirolimus±MTX, and evaluate the impact of the GVHD prophylaxis regimen on the outcomes. Median follow-up for alive patients was 29.0 months (9.5-97.0). The estimated 2-year overall survival (OS) for the CsA/MMF cohort was 55.6% (confidence interval 36.0, 71.3), and for the tacrolimus/sirolimus cohort it was 92.9% (63.3, 98.8) (P=.047). The probability of grade III or IV acute GVHD (aGVHD) was 60% for the CsA/MMF patients, and 10% for the tacrolimus/sirolimus group (P=.0102). No significant differences were seen for grade II to IV aGVHD ...

Impact of Cytomegalovirus (CMV) Reactivation after Umbilical Cord Blood Transplantation

Biology of Blood and Marrow Transplantation — Sun, 27 Sep 2009 00:00:00 +0100

This study investigated the impact of pretransplant cytomegalovirus (CMV) serostatus and posttransplant CMV reactivation and disease on umbilical cord blood transplant (UCBT) outcomes. Between 1994 and 2007, 332 patients with hematologic malignancies underwent UCBT and 54% were CMV seropositive. Pretransplant recipient CMV serostatus had no impact on acute or chronic graft-versus-host disease (aGVHD, cGVHD), relapse, disease-free survival (DFS), or overall survival (OS). There was a trend toward greater day 100 treatment-related mortality (TRM) in CMV-seropositive recipients (P=.07). CMV reactivation occurred in 51% (92/180) of patients with no difference in myeloablative (MA) versus reduced-intensity conditioning (RIC) recipients (P=.33). Similarly, reactivation was not influenced by the ...

A Pharmacokinetic Study of Plerixafor in Subjects with Varying Degrees of Renal Impairment

Biology of Blood and Marrow Transplantation — Sun, 27 Sep 2009 00:00:00 +0100

Plerixafor is a selective antagonist of CXCR4 used for mobilization of hematopoietic stem cells (HSCs) for autologous stem cell transplantation (SCT) in patients with multiple myeloma (MM) and non-Hodgkin lymphoma (NHL). This Phase 1 open-label study in healthy subjects was conducted to evaluate the pharmacokinetic characteristics of plerixafor in subjects with renal impairment. All subjects received a single 0.24 mg/kg subcutaneous dose of plerixafor. Subjects were stratified into 4 cohorts based on creatinine clearance determined from a 24-hour urine collection: control (>90 mL/min), mild renal impairment (51-80 mL/min), moderate renal impairment (31-50 mL/min), and severe renal impairment ( (Source: Biology of Blood and Marrow Transplantation)

Seventh Annual International Umbilical Cord Blood Transplantation Symposium, Los Angeles, California, June 5-6, 2009

Biology of Blood and Marrow Transplantation — Sun, 27 Sep 2009 00:00:00 +0100

The Seventh Annual International Cord Blood Transplantation Symposium was presented by the Cord Blood Forum and was partially supported by unrestricted educational grants from StemCyte International Cord Blood Center, the National Marrow Donor Program, and the Cleveland Cord Blood Center. The symposium also was partially supported by a contract between the Health Resources and Services Administration (HRSA), the US Department of Health and Human Services (HHS), and the Medical College of Wisconsin. (Source: Biology of Blood and Marrow Transplantation)

Patient-Reported Outcomes for Acute Graft-versus-Host Disease Prevention and Treatment Trials

Biology of Blood and Marrow Transplantation — Fri, 25 Sep 2009 00:00:00 +0100

This article summarizes issues to be considered in the use of PROs as endpoints in aGVHD prevention and treatment trials. (Source: Biology of Blood and Marrow Transplantation)

Erratum

Biology of Blood and Marrow Transplantation — Fri, 25 Sep 2009 00:00:00 +0100

In “Toll-Like Receptor 4 Polymorphisms and Risk of Gram-Negative Bacteremia after Allogeneic Stem Cell Transplantation. A Prospective Pilot Study” (Papanicolaou et al., Biol Blood Marrow Transplant. 2009:15(9):1130-1133) the authors should be listed as follows: Nana Yaa Mensah, Paolo Peterlongo, Peter Steinherz, Eric G. Pamer, Jaya Satagopan, Genovefa Anna Papanicolaou. (Source: Biology of Blood and Marrow Transplantation)

Proteasome Inhibition and Allogeneic Hematopoietic Stem Cell Transplantation: A Review

Biology of Blood and Marrow Transplantation — Fri, 25 Sep 2009 00:00:00 +0100

The proteasome and its associated ubiquitin protein modification system have proved to be an important therapeutic target in the treatment of multiple myeloma and other cancers. In addition to direct antitumor effects, proteasome inhibition also exerts strong effects on nonneoplastic immune cells. This indicates that proteasome inhibition, through the use of agents like bortezomib, could be used therapeutically to modulate immune responses. In this review we explore the emerging data, both preclinical and clinical, highlighting the importance of proteasome targeting of immunologic responses, primarily in the context of allogeneic hematopoietic stem cell transplantation (HSCT), both for the control of transplant-related toxicities like acute and chronic graft-versus-host disease (aGVHD, cGH...

The Preventive Health Behaviors of Long-Term Survivors of Cancer and Hematopoietic Stem Cell Transplantation Compared with Matched Controls

Biology of Blood and Marrow Transplantation — Thu, 24 Sep 2009 00:00:00 +0100

Little is known about the health promotion, prevention, and disease screening behaviors of cancer survivors treated with hematopoietic cell transplantation (HCT), who undergo arduous treatment and may be at particular risk for late effects and secondary malignancies. The purposes of this study were to examine the current health and secondary prevention behaviors of long-term HCT survivors compared with matched controls without cancer, and to identify sociodemographic and clinical factors associated with appropriate preventive practices. HCT survivors (n = 662) were drawn from 40 North American transplantation centers. Peer-nominated acquaintances of survivors matched on sex, age, education, and marital status served as controls (n = 158). Data were collected a mean of 6.7 years post-HCT (r...

Influence of Pretransplantation Restrictive Lung Disease on Allogeneic Hematopoietic Cell Transplantation Outcomes

Biology of Blood and Marrow Transplantation — Thu, 24 Sep 2009 00:00:00 +0100

We conducted a 15-year retrospective cohort study to determine the prevalence of restrictive lung disease before allogeneic hematopoietic cell transplantation (HCT), and to assess whether this was a risk factor for poor outcomes. A total of 2545 patients were eligible for the analysis. Restrictive lung disease was defined as a total lung capacity (TLC) < 80% of predicted normal. Chest x-rays and /or computed tomography (CT) scans were reviewed for all restricted patients to determine whether lung parenchymal abnormalities were unlikely or highly likely to cause restriction. Multivariate Cox proportional hazard and sensitivity analyses were performed to assess the relationship between restriction and early respiratory failure and nonrelapse mortality. Restrictive lung disease was present in...

Control of an Outbreak of Human Parainfluenza Virus 3 in Hematopoietic Stem Cell Transplant Recipients

Biology of Blood and Marrow Transplantation — Thu, 24 Sep 2009 00:00:00 +0100

Human parainfluenza virus 3 (HPIV3) infection can cause significant morbidity and mortality in patients undergoing hematopoietic stem cell transplantation (HSCT). There are no standard guidelines for the prevention and control of HPIV3 in the outpatient setting. After 2 HSCT inpatients diagnosed with HPIV3 were noted to have had multiple recent HSCT outpatient clinic (OPC) visits, an investigation of policy and procedures in the HSCT OPC was undertaken, and active surveillance for respiratory viral illness was instituted in the at-risk HSCT population. Between July 19 and August 30, 2005, 13 patients were diagnosed with HPIV3 infection. Morbidity in affected patients was significant, and mortality was high (38.5%) and not affected by antiviral therapy. Molecular typing identified several g...

Impending Challenges in the Hematopoietic Stem Cell Transplantation Physician Workforce

Biology of Blood and Marrow Transplantation — Thu, 24 Sep 2009 00:00:00 +0100

With increasing use of high dose chemotherapy with autologous and allogeneic transplants the need for the transplant physician workforce requires reassessment. The types of transplants and patients are also shifting toward transplants being done in patients with more comorbidities and more commonly these types of patients require more work effort per patient from the transplant physician. Additionally, HSCT survivors often require ongoing care at the transplant center due to the inability of the primary care workforce or the hematology/oncology workforce to absorb caring for post complex post transplant patients. The adult transplant workforce has had very few physicians join under age 40. Nearly 50% of adult transplant physicians are over age 50 whereas only 28% of pediatric transplant ph...

Current Status and Perspectives of Tyrosine Kinase Inhibitor Treatment in the Posttransplant Period in Patients with Chronic Myelogenous Leukemia (CML)

Biology of Blood and Marrow Transplantation — Wed, 23 Sep 2009 00:00:00 +0100

In conclusion, TKIs of the first- and second-generation are promising options for the posttransplant period of patients with CML, but algorithms for dosage, intervals from SCT, duration of application, and the combination with donor lymphocytes still have to be developed. (Source: Biology of Blood and Marrow Transplantation)

Cord Blood Transplantation from Unrelated Donors in Adults with High-Risk Acute Myeloid Leukemia

Biology of Blood and Marrow Transplantation — Wed, 23 Sep 2009 00:00:00 +0100

Clinical studies focused on disease-specific outcomes of cord blood transplant (CBT) from unrelated donors are limited. We analyzed the outcome and prognostic factors of 49 adults with high-risk acute myelogenous leukemia (AML) receiving single-unit CBT from unrelated donors after myeloablative (MA) conditioning at a single institution. Conditioning regimens were based on the combination of thiotepa, busulfan (Bu), cyclophospamide (Cy), or fludarabine (Flu), and antithymocyte globulin (ATG). Cumulative incidence of myeloid and platelet engraftment was 96% and 73% at a median time of 20 and 62 days, respectively. Engraftment was significantly faster for patients receiving higher doses of CD34+ cells. Confidence Interval of graft-versus-host disease (GVHD), acute GVHD (aGVHD) grade II-IV, II...

Low Nonrelapse Mortality and Prolonged Long-Term Survival after Reduced-Intensity Allogeneic Stem Cell Transplantation for Relapsed or Refractory Diffuse Large B Cell Lymphoma: Report of the Société Française de Greffe de Moelle et de Thérapie Cellulaire

Biology of Blood and Marrow Transplantation — Wed, 23 Sep 2009 00:00:00 +0100

Patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) have a very poor prognosis. However, they may achieve long-term survival by undergoing allogeneic stem cell transplantation (SCT). The purpose of this study was to assess the outcome of all adult patients with DLBCL whose treatment included a reduced-intensity conditioning (RIC) regimen for allogeneic SCT and whose data were reported in the French Society of Marrow Transplantation and Cellular Therapy registry. Sixty-eight patients (median age: 48 years) were transplanted from October 1998 to January 2007. They had received a median of 2 regimens of therapy prior to allogeneic SCT, and 54 (79%) had already undergone SCT. Prior to transplantation, 32 patients (47%) were in complete remission (CR). For all patients bu...

Antiviral Responses following L-Leucyl-L-Leucine Methyl Esther (LLME)-Treated Lymphocyte Infusions: Graft-versus-Infection without Graft-versus-Host Disease

Biology of Blood and Marrow Transplantation — Wed, 23 Sep 2009 00:00:00 +0100

Although allogeneic hematopoietic progenitor cell transplant (HPCT) is curative therapy for many disorders, it is associated with significant morbidity and mortality, which can be related to graft-versus-host disease (GVHD) and the immunosuppressive measures required for its prevention and/or treatment. Whether the immunosuppression is pharmacologic or secondary to graft manipulation, the graft recipient is left at increased risk of the threatening opportunistic infection. Refractory viral diseases in the immunocompromised host have been treated by infusion of virus-specific lymphotyces and by unmanipulated donor lymphocyte infusion (DLI) therapy. L-leucyl-L-leucine methyl ester (LLME) is a compound that induces programmed cell death of natural killer (NK) cells, monocytes, granulocytes, m...

“Short Course” Bortezomib plus Melphalan and Prednisone as Induction Prior to Transplant or as Frontline Therapy for Nontransplant Candidates in Patients with Previously Untreated Multiple Myeloma

Biology of Blood and Marrow Transplantation — Tue, 22 Sep 2009 00:00:00 +0100

The purpose of this study was to evaluate the efficacy and safety of short-course bortezomib, melphalan, prednisone (VMP) in previously untreated multiple myeloma as frontline therapy for transplant-ineligible patients and induction prior to autologous stem cell transplantation (ASCT). Patients received up to 6 28-day cycles of bortezomib 1.3 mg/m2, days 1, 4, 8, and 11, plus melphalan 6 mg/m2 and prednisone 60 mg/m2, days 1-7. After 2-6 cycles, eligible and consenting patients could proceed to ASCT. Responses were assessed by International Uniform Response Criteria. The primary endpoint was complete response (CR) rate with VMP. Forty-five patients were enrolled. Among 44 evaluable patients, response rate was 95%, including 18% ≥CR (9% stringent CR), 27% very good partial responses (VGPR...

Validation of The National Institutes of Health (NIH) Scale for Oral Chronic Graft-versus-Host Disease (cGVHD)

Biology of Blood and Marrow Transplantation — Fri, 18 Sep 2009 00:00:00 +0100

The aim of this study was to validate the 2005-2006 National Institutes of Health (NIH) scale for patient's self-reporting and clinical manifestations of oral chronic graft-versus-host disease (cGVHD). Numerical parameters of the NIH scale were analyzed for their construct validity (correlation of the NIH scale with numerical rating scale [NRS] for pain) and internal consistency reliability (correlation between different parameters of the same scale). Categoric parameters were analyzed by comparison between severity subgroups defined by the oral manifestation (lichenoid/erythema/ulceration). Analysis included data of 75 evaluations. The total NIH score and the NRS for pain were found to be moderately correlated (r=0.449). Cronbach's alpha reliability coefficient was .718. Strong correlatio...

Lung Function and Long-Term Complications after Allogeneic Hematopoietic Cell Transplant

Biology of Blood and Marrow Transplantation — Wed, 16 Sep 2009 00:00:00 +0100

The objective of this study was to determine if posttransplant lung function is associated with 5-year nonrelapse mortality (NRM) and the development of chronic graft-versus-host disease (cGVHD). Retrospective analysis was done for 2158 patients who had routine pulmonary function testing 60-120 days after transplant between 1992 and 2004. Cox regression was used to assess the hazard ratio for 5-year NRM. A second analysis assessed the hazard ratio for the development of cGVHD. Lung function score was the primary exposure, and was calculated according to forced expiratory volume in 1 second (FEV1) and carbon monoxide diffusion capapcity (DLCO). Individual pulmonary function parameters were secondary exposures. The primary outcomes were 5-year NRM and the development of cGVHD. Most patients ...

Hepatic Safety of Voriconazole after Allogeneic Hematopoietic Stem Cell Transplantation

Biology of Blood and Marrow Transplantation — Mon, 14 Sep 2009 00:00:00 +0100

Voriconazole is increasingly used in allogeneic hematopoietic stem cell transplantation (HSCT) for prophylaxis and treatment of fungal infections. Hepatic dysfunction is common in patients undergoing HSCT and may have an impact on the clinical decision to institute voriconazole. We conducted a retrospective review of all adult and pediatric HSCT recipients who received >2 consecutive doses of voriconazole between January 2005 and February 2008. Clinical hepatotoxicity was defined as the subjective attribution of liver enzyme elevation (even a mild one) to hepatotoxicity because of voriconazole by the treating physician and leading to discontinuation of voriconazole. Biochemical hepatotoxicity was defined as an elevation in one or more liver enzymes to >3 times the upper limit of normal or ...

A Comparison of HLA-Identical Sibling Allogeneic versus Autologous Transplantation for Diffuse Large B Cell Lymphoma: A Report from the CIBMTR

Biology of Blood and Marrow Transplantation — Mon, 14 Sep 2009 00:00:00 +0100

We compared outcomes of 916 diffuse large B cell lymphoma (DLBCL) patients aged ≥18 years undergoing first autologous (n = 837) or myeloablative (MA) allogeneic hematopoietic cell transplant (HCT) (n = 79) between 1995 and 2003 reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). Median follow-up was 81 months for allogeneic HCT versus 60 months for autologous HCT. Allogeneic HCT recipients were more likely to have high-risk disease features including higher stage, more prior chemotherapy regimens, and resistant disease. Allogeneic HCT was associated with a higher 1 year treatment-related mortality (TRM) (relative risk [RR] 4.88, 95% confidence interval [CI], 3.21-7.40, P < .001), treatment failure (RR 2.06, 95% CI, 1.54-2.75, P < .001), and mortality (...

Impact of Cyclosporine-A Concentration on the Incidence of Severe Acute Graft-versus-Host Disease after Allogeneic Stem Cell Transplantation

Biology of Blood and Marrow Transplantation — Mon, 14 Sep 2009 00:00:00 +0100

This single-center retrospective study analyzed 85 consecutive patients who underwent allogeneic stem cell transplantation (allo-SCT) with the aim to assess whether there is a correlation between exposure to cyclosporine-A (CsA; as measured by CsA concentrations during the first month after allo-SCT) and the risk for developing severe grade III-IV acute graft-versus-host disease (aGVHD). The median concentrations of CsA in the blood at 1, 2, 3, and 4 weeks after allo-SCT were 348 (range: 172-733), 284 (range: 137-535), 274 (range: 107-649), and 247 (range: 37-695) ng/mL, respectively. Overall, grade II-IV aGVHD occurred in 36 patients (42%) at a median of 29 (range: 6-100) days after allo-SCT. The incidence of grade III-IV aGVHD (n = 20) was 23% (95% confidence interval [CI], 14%-32%). In ...

Impact of Conditioning Regimen in Allogeneic Hematopoetic Stem Cell Transplantation for Children with Acute Myelogenous Leukemia beyond First Complete Remission: A Pediatric Blood and Marrow Transplant Consortium (PBMTC) Study

Biology of Blood and Marrow Transplantation — Mon, 14 Sep 2009 00:00:00 +0100

Total body irradiation (TBI)-based conditioning regimens for pediatric patients with acute myelogenous leukemia (AML) beyond first complete remission (CR1) are controversial. Because the long-term morbidity of busulfan (Bu)-based regimens appears to be lower, determining efficacy is critical. We retrospectively evaluated 151 pediatric patients with AML beyond CR1, comparing outcomes in 90 patients who received a TBI-based conditioning regimen and 61 patients who received a Bu-based conditioning regimen. There were no differences between the 2 groups with respect to age, sex, duration of CR1, time from most recent remission to transplantation, or donor source. The probability of relapse at 2 years also did not differ between the 2 groups (26% and 27%, respectively; P=.93). No significant di...

Tacrolimus/Methotrexate versus Cyclosporine/Methotrexate as Graft-versus-Host Disease Prophylaxis in Patients with Severe Aplastic Anemia Who Received Bone Marrow Transplantation from Unrelated Donors: Results of Matched Pair Analysis

Biology of Blood and Marrow Transplantation — Mon, 14 Sep 2009 00:00:00 +0100

Tacrolimus (FK) and cyclosporine (CsA) have been shown to be effective in the prophylaxis of graft-versus-host disease (GVHD). However, no comparative studies have yet been conducted to examine the efficacy of FK/methotrexate (MTX) and CsA/MTX in patients with severe aplastic anemia (SAA) given unrelated donor bone marrow transplantation (U-BMT). We used matched-pair analysis to compare FK/MTX with CsA/MTX in patients with SAA who received U-BMT through the Japan Marrow Donor Program. Forty-seven pairs could be matched exactly for recipient age and conditioning regimens. Forty-five patients achieved engraftment in the FK group and 42 patients in the CsA group. The probability of grade II-IV acute GVHD (aGVHD) was 28.9% in the FK group and 32.6% in the CsA group (P=.558). The probability of...

Polymorphism of Interleukin-23 Receptor Gene But Not of NOD2/CARD15 Is Associated with Graft-versus-Host Disease after Hematopoietic Stem Cell Transplantation in Children

Biology of Blood and Marrow Transplantation — Mon, 14 Sep 2009 00:00:00 +0100

Abstract: Graft-versus-host disease (GVHD) is a major cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). The selection of a suitable donor is the most critical issue in preventing severe GVHD. Recent data suggest that the risk of GVHD does not only depend on human leukocyte antigens (HLA) but also on polymorphisms of genes that influence immune responses. We analyzed the 1142 G>A single-nucleotide polymorphism (SNP) in the interleukin-23 receptor gene (IL23R) and 3 SNPs in the NOD2/CARD15 gene in a cohort of 231 children who underwent allogeneic stem cell transplantation and/or their respective donors. No association was observed between any of the NOD2/CARD15 polymorphisms and GVHD in either donor or recipient. Likewise, the IL23R polymorphism in the re...

A Novel GVHD-Prophylaxis with Low-Dose Alemtuzumab in Allogeneic Sibling or Unrelated Donor Hematopoetic Cell Transplantation: The Feasibility of Deescalation

Biology of Blood and Marrow Transplantation — Mon, 14 Sep 2009 00:00:00 +0100

In conclusion, we demonstrate the feasibility of reducing the dose of alemtuzumab as GVHD-prophylaxis to 10 mg absolute in combination with CsA only for UD transplantation in particular. (Source: Biology of Blood and Marrow Transplantation)

Race and Socioeconomic Status Influence Outcomes of Unrelated Donor Hematopoietic Cell Transplantation

Biology of Blood and Marrow Transplantation — Mon, 14 Sep 2009 00:00:00 +0100

Success of hematopoietic cell transplantation (HCT) can vary by race, but the impact of socioeconomic status (SES) is not known. To evaluate the role of race and SES, we studied 6207 unrelated-donor myeloablative (MA) HCT recipients transplanted between 1995 and 2004 for acute or chronic leukemia or myelodysplastic syndrome (MDS). Patients were reported by transplant center to be White (n = 5253), African American (n = 368), Asian/Pacific-Islander (n = 141), or Hispanic (n = 445). Patient income was estimated from residential zip code at time of HCT. Cox regression analysis adjusting for other significant factors showed that African American (but not Asian or Hispanic) recipients had worse overall survival (OS) (relative-risk [RR] 1.47; 95% confidence interval [CI] 1.29-1.68, P < .001) com...

Infectious Complications after Unrelated Umbilical Cord Blood Transplantation in Adult Patients with Hematologic Malignancies

Biology of Blood and Marrow Transplantation — Mon, 14 Sep 2009 00:00:00 +0100

In conclusion, this data suggests that UCBT can be performed in adult patients with hematologic malignancies with an acceptable incidence of IRM provided a sufficient dose of nucleated cells is infused to the patient. (Source: Biology of Blood and Marrow Transplantation)

Blocking LFA-1 Activation with Lovastatin Prevents Graft-versus-Host Disease in Mouse Bone Marrow Transplantation

Biology of Blood and Marrow Transplantation — Mon, 14 Sep 2009 00:00:00 +0100

Graft-versus-host disease (GVHD) following bone marrow transplantation (BMT) is mediated by alloreactive donor T lymphocytes. Migration and activation of donor-derived T lymphocytes play critical roles in the development of GVHD. Leukocyte function–associated antigen-1 (LFA-1) regulates T cell adhesion and activation. We previously demonstrated that the I-domain, the ligand-binding site of LFA-1, changes from the low-affinity state to the high-affinity state on LFA-1 activation. Therapeutic antagonists, such as statins, inhibit LFA-1 activation and immune responses by modulating the affinity state of the LFA-1 I-domain. In the present study, we report that lovastatin blocked mouse T cell adhesion, proliferation, and cytokine production in vitro. Furthermore, blocking LFA-1 in the low-aff...

A Phase III Study of Infliximab and Corticosteroids for the Initial Treatment of Acute Graft-versus-Host Disease

Biology of Blood and Marrow Transplantation — Fri, 11 Sep 2009 00:00:00 +0100

Anti-Tumor Necrosis Factor Alpha (TNF-α) therapy with infliximab has shown to be effective for patients with steroid-refractory acute graft-versus-host disease (aGVHD). An open-labeled, phase III trial was conducted to determine if the addition of infliximab to steroids could improve results for patients with newly diagnosed grade II-IV aGVHD. A total of 63 patients were randomized either to 2 mg/kg/day methylprednisolone (MP) or infliximab+ MP. Average age was 47 years (range: 20-70 years); 64% were male. Fifty-three percent and 51% of patients received a matched-sibling and/or bone marrow (BM) graft. Sixty-seven percent had grade II, 33% grade III-IV aGVHD; 62% had skin, 53% gastrointestinal (GI), and 7% had liver involvement. At days 7 and 28, the response rate for infliximab+ MP versu...

Endovenous Administration of Bone Marrow-Derived Multipotent Mesenchymal Stromal Cells Prevents Renal Failure in Diabetic Mice

Biology of Blood and Marrow Transplantation — Thu, 10 Sep 2009 23:00:00 +0100

Twenty-five to 40% of diabetic patients develop diabetic nephropathy, a clinical syndrome that comprises renal failure and increased risk of cardiovascular disease. It represents the major cause of chronic kidney disease and is associated with premature morbimortality of diabetic patients. Multipotent mesenchymal stromal cells (MSC) contribute to the regeneration of several organs, including acutely injured kidney. We sought to evaluate if MSC protect kidney function and structure when endovenously administered to mice with severe diabetes. A month after nonimmunologic diabetes induction by streptozotocin injection, C57BL/6 mice presented hyperglycemia, glycosuria, hypoinsulinemia, massive β-pancreatic islet destruction, low albuminuria, but not renal histopathologic changes (DM mice). At...

Biology of Blood and Marrow Transplantation — Thu, 10 Sep 2009 16:37:25 +0100

(Source: Biology of Blood and Marrow Transplantation)

Officers and Directors of ASBMT

Biology of Blood and Marrow Transplantation — Thu, 10 Sep 2009 16:37:25 +0100

(Source: Biology of Blood and Marrow Transplantation)

Editorial Board

Biology of Blood and Marrow Transplantation — Thu, 10 Sep 2009 16:37:25 +0100

(Source: Biology of Blood and Marrow Transplantation)

Masthead

Biology of Blood and Marrow Transplantation — Thu, 10 Sep 2009 16:37:25 +0100

(Source: Biology of Blood and Marrow Transplantation)

Erratum

Biology of Blood and Marrow Transplantation — Thu, 10 Sep 2009 16:37:25 +0100

In “A Phase II Trial of Autologous Stem Cell Transplant followed by Mini-Allogeneic Stem Cell Transplant for the Treatment of Multiple Myeloma: An Analysis of Eastern Cooperative Oncology Group ECOG E4A98 and E1A97” (Vesole et al., Biol Blood Marrow Transplant. 2009:15:83-91) an author was omitted. The additional author is Carol A. Huff, M.D., of Johns Hopkins University, Baltimore, Maryland. (Source: Biology of Blood and Marrow Transplantation)

2010 BMT Tandem Meetings Will Be Feb. 24–28 in Orlando

Biology of Blood and Marrow Transplantation — Thu, 10 Sep 2009 16:37:25 +0100

The combined 2010 annual meetings of ASBMT and the Center for International Blood and Marrow Transplant Research (CIBMTR) will be Feb. 24-28 at the Rosen Shingle Creek Convention Center in Orlando, Fla. (Source: Biology of Blood and Marrow Transplantation)

Guidelines for Preventing Infectious Complications among Hematopoietic Cell Transplantation Recipients: A Global Perspective

Biology of Blood and Marrow Transplantation — Thu, 10 Sep 2009 16:37:22 +0100

Marcie Tomblyn, University of Minnesota, Minneapolis, MN (Source: Biology of Blood and Marrow Transplantation)

Antibody Response to Polysaccharide Conjugate Vaccines after Nonmyeloablative Allogeneic Stem Cell Transplantation

Biology of Blood and Marrow Transplantation — Thu, 10 Sep 2009 00:00:00 +0100

In this study, the reconstitution of humoral immunity after allo-RIST is determined by measuring the vaccination-induced antibody response against Streptococcus pneumoniae, Haemophilus influenzae type b (Hib), and tetanus toxoid (TT) 1 year posttransplantation. Patients who underwent allo-RIST were vaccinated according to a schedule starting at 12 months following transplantation with conjugated vaccines against S. pneumoniae, Hib, and TT. Of twenty-six patients both pre- and postvaccination sera were available. Patients were required to be off immunosuppression at the time of vaccination, and, therefore, 9 of the 26 patients did not start vaccination at 12 months post-stem cell transplantation but rather at a median range of 15 (12-36 months) posttransplantation. Except for pneumococcal s...

Impact of Pre-transplant Rituximab on Survival after Autologous Hematopoietic Stem Cell Transplantation for Diffuse Large B Cell Lymphoma

Biology of Blood and Marrow Transplantation — Wed, 09 Sep 2009 23:00:00 +0100

Incorporation of the anti-CD20 monoclonal antibody rituximab into front-line regimens to treat diffuse large B cell lymphoma (DLBCL) has resulted in improved survival. Despite this progress, however, many patients develop refractory or recurrent DLBCL and then undergo autologous hematopoietic stem cell transplantation (AuHCT). It is unclear to what extent pre-transplant exposure to rituximab affects outcomes after AuHCT. Outcomes of 994 patients receiving AuHCT for DLBCL between 1996 and 2003 were analyzed according to whether rituximab was (n = 176; +R cohort) or was not (n = 818; −R cohort) administered with front-line or salvage therapy before AuHCT. The +R cohort had superior progression-free survival (PFS; 50% vs 38%; P = .008) and overall survival (OS; 57% vs 45%; P = .006) at 3 ye...

Donor KIR3DL1/3DS1 Gene and Recipient Bw4 KIR Ligand as Prognostic Markers for Outcome in Unrelated Hematopoietic Stem Cell Transplantation

Biology of Blood and Marrow Transplantation — Wed, 09 Sep 2009 23:00:00 +0100

Given their antileukemic activity, natural killer (NK) cells can alter the outcome of hematopoietic stem cell transplantation (HSCT). The physiologic functions of NK cells are regulated by the interaction of killer immunoglobulin-like receptors (KIR) with specific HLA class I ligands. In the literature, different models based on HLA class I and/or KIR donor (D)/recipient (R) gene disparities are considered as predictors of NK cell alloreactivity. In this retrospective and multicentric French study, we analyzed the clinical impact of the different NK-alloreactivity models in 264 patients who underwent T repleted unrelated HSCT. First, we did not observe that the “KIR ligand-ligand” model had a significant clinical impact on unrelated HSCT outcome, whereas the “missing KIR ligand” mo...

The National Marrow Donor Program's Symposium on Patient Advocacy in Cellular Transplantation Therapy: Addressing Barriers to Hematopoietic Cell Transplantation

Biology of Blood and Marrow Transplantation — Mon, 07 Sep 2009 00:00:00 +0100

This report summarizes the symposium's deliberations and recommendations to address persistent patient barriers throughout the transplantation process. (Source: Biology of Blood and Marrow Transplantation)

Diagnostic Tools in the Indications for Allogeneic Stem Cell Transplantation in Myelodysplastic Syndromes

Biology of Blood and Marrow Transplantation — Mon, 07 Sep 2009 00:00:00 +0100

The rates of allogeneic stem cell transplantation (SCT) to treat the myelodysplastic syndromes (MDS) is continually increasing. However, given the growing arsenal of therapeutic options in parallel to deeper insight into the heterogeneity of this disorder, determining the indications for SCT in MDS remains a difficult task. The International Prognostic Scoring System (IPSS) serves as a guideline for therapeutic decisions, but many aspects (eg, interpretation of rare cytogenetic abnormalities, combinations of chromosomal alterations and/or molecular markers, variant clinical courses within distinct biological subgroups) remain the subject of continuous investigation. In an effort to achieve a more well-differentiated risk categorization, attempts have been made to perform a more detailed cy...

A “No-wash” Albumin-Dextran Dilution Strategy for Cord Blood Unit Thaw: High Rate of Engraftment and a Low Incidence of Serious Infusion Reactions

Biology of Blood and Marrow Transplantation — Mon, 07 Sep 2009 00:00:00 +0100

Preparation of cord blood (CB) units for infusion by albumin-dextran dilution without centrifugation may be advantageous for adult patients to minimize cell loss and, unlike a bedside thaw, is still conducted in the controlled laboratory environment. Therefore, we studied CB transplantation (CBT) using this technique in 54 consecutive CBT recipients >20 kg. Patients (median age=42 years [range: 7-66 years]; median weight=71 kg [range: 24-109]) were transplanted for high-risk hematologic malignancies with myeloablative (n=35) or nonmyeloablative (n=19) conditioning and 4-6/6 human leukocyte antigen (HLA)-matched double-unit grafts. One hundred seven units were thawed with dilution, whereas 1 red blood cell (RBC)-replete unit was washed. A 5:1 dextran 40%/25% albumin solution was used. RBC-d...

Incidence of Viral and Fungal Infections following Busulfan-Based Reduced-Intensity versus Myeloablative Conditioning in Pediatric Allogeneic Stem Cell Transplantation Recipients

Biology of Blood and Marrow Transplantation — Mon, 07 Sep 2009 00:00:00 +0100

Reductions in the duration and nadir of neutropenia have translated into a significant decrease in bacteremia in adult recipients of allogeneic stem cell transplantation (allo-SCT) with reduced-intensity conditioning (RIC) during the first 30 days after transplantation. It remains to be determined whether RIC allo-SCT also will result in a decrease in systemic viral infections (SVIs) and invasive fungal infections (IFIs), which are more dependent on alterations in cellular immunity. We compared the incidence of SVIs and IFIs in children receiving busulfan-based RIC allo-SCT and in children receiving myeloablative conditioning (MAC) allo-SCT for various malignant and nonmalignant diseases. Allo-SCT recipients at risk for cytomegalovirus (CMV) received ganciclovir/foscarnet, and most of the ...

Successful Stem Cell Remobilization Using Plerixafor (Mozobil) Plus Granulocyte Colony-Stimulating Factor in Patients with Non-Hodgkin Lymphoma: Results from the Plerixafor NHL Phase 3 Study Rescue Protocol

Biology of Blood and Marrow Transplantation — Mon, 07 Sep 2009 00:00:00 +0100

In a phase 3 multicenter, randomized, double-blinded, placebo-controlled study of 298 patients with non-Hodgkin lymphoma (NHL), granulocyte colony-stimulating factor (G-CSF) plus plerixafor increased the proportion of patients who mobilized ≥5 × 106 CD34+ hematopoietic stem cells (HSCs)/kg compared with placebo plus G-CSF (P < .001). Patients in either study arm who failed mobilization (< 0.8 × 106 CD34+ cells/kg in 2 collections or (Source: Biology of Blood and Marrow Transplantation)

Pertussis Immunity and Response to Tetanus-Reduced Diphtheria-Reduced Pertussis Vaccine (Tdap) after Autologous Peripheral Blood Stem Cell Transplantation

Biology of Blood and Marrow Transplantation — Mon, 07 Sep 2009 00:00:00 +0100

Pertussis is a highly contagious respiratory infection characterized by prolonged cough and inspiratory whoop. Despite widespread vaccination of children aged2-fold response to PT following vaccination with Tdap. These data suggest that autologous transplantation recipients are highly susceptible to pertussis and that immunization with 2.5μg of PT induces an inadequate response. Prospective trials evaluating BOOSTRIX, containing 8μg/dose of PT (approved for adults in December 2008) are warranted in this vulnerable population undergoing transplantation. (Source: Biology of Blood and Marrow Transplantation)

Receiving Information on Fertility- and Menopause-Related Treatment Effects among Women Who Undergo Hematopoietic Stem Cell Transplantation: Changes in Perceived Importance Over Time

Biology of Blood and Marrow Transplantation — Sun, 06 Sep 2009 23:00:00 +0100

Hematopoietic stem-cell transplantation (HSCT) is associated with high rates of gonadal failure, which is distressing for younger patients desiring to start a family. The perceived importance and optimal timing of discussing fertility- and menopause-related information with women undergoing aggressive treatment such as HSCT is not well defined. Questionnaires were sent to 532 patients who underwent HSCT between January 1987 and September 2004 at the ages of 16 to 50 years. The questionnaire assessed demographic data, the need for fertility- and menopause-related information at various times during treatment, and standardized measures of anxiety, quality of life, and menopausal symptoms. The return rate was 40.2%, with 196 patients participating. Of these, 38% reported that they had discuss...

Dichotomous Role of Interferon-γ in Allogeneic Bone Marrow Transplant

Biology of Blood and Marrow Transplantation — Sun, 06 Sep 2009 23:00:00 +0100

Interferon (IFN)-γ is a pleiotropic cytokine with a central role in innate and adaptive immunity. As a potent pro-inflammatory and antitumor cytokine, IFN-γ is conventionally thought to be responsible for driving cellular immune response. On the other hand, accumulating evidence suggests that IFN-γ also has immunosuppressive activity. An important role for IFN-γ in inhibiting graft-versus-host disease (GVHD) has been demonstrated in murine models, despite IFN-γ being one of the key factors amplifying T cell activation during the process of acute GVHD (aGVHD), the major complication and cause of post-transplant mortality in allogeneic bone marrow transplantation (BMT). At the same time, IFN-γ facilitates graft-versus-leukemia (GVL) activity. Dissociation of GVL effects from GVHD has b...

Older Age But Not Donor Health Impairs Allogeneic Granulocyte Colony-Stimulating Factor (G-CSF) Peripheral Blood Stem Cell Mobilization

Biology of Blood and Marrow Transplantation — Thu, 03 Sep 2009 23:00:00 +0100

We evaluated stem cell mobilization in 195 consecutive sibling donors who underwent a uniform mobilization regimen of granulocyte colony-stimulating factor (G-CSF) at 10μg/kg/day divided into twice daily dosing. On day 5, peripheral blood (PB) CD34 cells/μL were measured immediately prior to peripheral blood stem cell (PBSC) apheresis. Failed mobilization was defined as (Source: Biology of Blood and Marrow Transplantation)

Reduced-Intensity Conditioning followed by Peripheral Blood Stem Cell Transplantation for Adult Patients with High-Risk Acute Lymphoblastic Leukemia

Biology of Blood and Marrow Transplantation — Wed, 02 Sep 2009 23:00:00 +0100

Acute lymphoblastic leukemia (ALL) with high-risk features has a poor prognosis in adults despite aggressive chemotherapy. Reduced-intensity conditioning (RIC) is a lower toxicity alternative for high-risk patients requiring hematopoietic cell transplantation (HCT); however, it has not been widely used for ALL. We conducted a retrospective study of 24 high-risk adult ALL patients who received an RIC regimen of fludarabine (Flu)/melphalan (Mel) prior to allogeneic peripheral blood stem cell transplantation (PBSCT) between 6/14/02 and 6/15/07 at the City of Hope. Indications for the RIC regimen were: (1) aged 50 years or older (42%), (2) compromised organ function (54%), or (3) recipient of a previous HCT (37.5%). Patients had a median age of 47.5 years and the median follow-up was 28.5 mont...

Impact of Declining Fertility Rates in Canada on Donor Options in Blood and Marrow Transplantation

Biology of Blood and Marrow Transplantation — Wed, 02 Sep 2009 00:00:00 +0100

An HLA-matched sibling remains the optimal donor for most patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Marked declines in total fertility rates in Canada over the past 50 years will lead to increasing numbers of patients without sibling donors well into the future. We retrieved transplantation data from a Canadian center and the Canadian Blood and Marrow Transplant Group and total fertility data from the United Nations Department of Economic and Social Affairs. The mean age of adults with acute myelogenous leukemia (AML), who underwent transplantation at The Ottawa Hospital between 1995 and 2004, was 41 ± 12 years (n = 87). The chance of finding 1 or more HLA-matched sibling donors for a patient with AML treated in 2002 is reflected by the total fertility...

Defining the Intensity of Conditioning Regimens: Working Definitions

Biology of Blood and Marrow Transplantation — Wed, 02 Sep 2009 00:00:00 +0100

This report also assigns commonly used regimens to one of these categories, based upon the agents, dose, or combinations. Standardized classification of conditioning regimen intensities will allow comparison across studies and interpretation of study results. (Source: Biology of Blood and Marrow Transplantation)

Comparison of Clinical Outcomes of Patients with Relapsed Acute Promyelocytic Leukemia Induced with Arsenic Trioxide and Consolidated with Either an Autologous Stem Cell Transplant or an Arsenic Trioxide–Based Regimen

Biology of Blood and Marrow Transplantation — Tue, 01 Sep 2009 23:00:00 +0100

In patients with relapsed acute promyelocytic leukemia (APL), the best consolidation regimen following induction of remission with arsenic trioxide (ATO) remains to be defined. Since January 2000, 37 patients with relapsed APL were treated at our center. The median age was 34 years (range, 6-57 years), and there were 20 males (54.1%). The median duration of first remission was 20.3 months (range, 2.9-81.2 months). Relapse was treated with single-agent ATO in 22 patients (59.5%), ATO+ATRA in 5 patients (13.5%), and ATO+ATRA + anthracycline in 10 patients (27%). Thirty-three patients (89%) achieved molecular remission after induction and a consolidation course. Fourteen patients opted to undergo autologous stem cell transplantation (SCT), and the remaining 19 patients received monthly cycles...

Busulfan and Cyclophosphamide (Bu/Cy) as a Preparative Regimen for Autologous Stem Cell Transplantation in Patients with Non-Hodgkin Lymphoma: A Single-Institution Experience

Biology of Blood and Marrow Transplantation — Tue, 01 Sep 2009 23:00:00 +0100

This study is a retrospective analysis of 78 consecutive patients with NHL who underwent ASCT with Bu/Cy at Massachusetts General Hospital Cancer Center. Data were collected through review of electronic medical records. A total of 78 patients with NHL underwent ASCT with Bu/Cy preparative therapy between 1996 and 2006. Median follow-up for survivors was 5.0 years (range, 6 months to 12 years). Significant transplantation-associated complications included 9 documented bacterial infections, 4 cases of engraftment syndrome, 3 cases of hepatic veno-occlusive disease (VOD), 6 cases of cardiac complications, and 2 cases of pulmonary fibrosis. The 100-day treatment-related mortality (TRM) was 1%. At 3 years, progression-free survival (PFS) was 48% (95% confidence interval [CI]=37% to 59%) and ove...

Early and Late Neurological Complications after Reduced-Intensity Conditioning Allogeneic Stem Cell Transplantation

Biology of Blood and Marrow Transplantation — Tue, 01 Sep 2009 23:00:00 +0100

In conclusion, our study showed that NC are observed after allo-RIC and have diverse features. NC affecting the CNS have earlier onset and worse outcome than those involving the PNS. (Source: Biology of Blood and Marrow Transplantation)

Quantifying the Survival Benefit for Allogeneic Hematopoietic Stem Cell Transplantation in Relapsed Acute Myelogenous Leukemia

Biology of Blood and Marrow Transplantation — Tue, 01 Sep 2009 23:00:00 +0100

Allogeneic hematopoietic stem cell transplantation (HSCT) is the recommended therapy for patients with relapsed acute myelogenous leukemia (AML), despite little evidence showing a survival benefit in patients who undergo HSCT versus chemotherapy alone. Because a prospective randomized trial addressing this issue is unlikely, we retrospectively reviewed all patients receiving initial salvage therapy for AML at M.D. Anderson Cancer Center between 1995 and 2004, focusing on patients undergoing HSCT or chemotherapy without HSCT as second salvage after first salvage failed to produce complete remission (CR) (group A) and patients in first salvage–induced CR (group B). Median survival was 5.1 months for HSCT (n=84) versus 2.3 months for chemotherapy (n = 200; P = .004) in group A and 11.7 mont...

Improved Nonrelapse Mortality and Infection Rate with Lower Dose of Antithymocyte Globulin in Patients Undergoing Reduced-Intensity Conditioning Allogeneic Transplantation for Hematologic Malignancies

Biology of Blood and Marrow Transplantation — Tue, 01 Sep 2009 23:00:00 +0100

We sought to reduce the risk of infectious complications and nonrelapse mortality (NRM) associated with the use of antithymocyte globulin (ATG) without compromising control of acute graft-versus-host disease (aGVHD) in patients undergoing reduced-intensity conditioning (RIC) transplantation. As part of an ongoing quality improvement effort, we lowered the dose of rabbit ATG from 7.5 mg/kg of ATG (R-ATG) (n = 39) to 6.0 mg/kg of ATG (r-ATG) (n = 33) in association with fludarabine (Flu) and busulfan (BU) RIC transplantation and then monitored patients for adverse events, relapse, and survival. Of the 72 mostly high risk (82%) patients studied, 89% received unrelated donor allografts, 25% of which were HLA-mismatched. No differences in posttransplantation full donor-cell chimerism rates were...

Decision Analysis of Peripheral Blood versus Bone Marrow Hematopoietic Stem Cells for Allogeneic Hematopoietic Cell Transplantation

Biology of Blood and Marrow Transplantation — Tue, 01 Sep 2009 23:00:00 +0100

Peripheral blood stem cells (PBSCs) and bone marrow (BM) hematopoietic stem cells represent therapeutic alternatives in allogeneic hematopoietic cell transplantation. Randomized controlled trials and an individual patient data meta-analysis (IPDMA) have demonstrated a decreased risk of disease relapse and an increased risk of acute and chronic graft-versus-host disease (aGVHD, cGVHD) in patients receiving PBSCs compared with those receiving BM stem cells. Decision modeling provides quantitative integration of the risks and benefits associated with these alternative treatments, incorporates survival discounts for lower quality of life in patients with aGVHD or cGVHD and post-transplantation relapse, and allows sensitivity analyses for all model assumptions. We have constructed an externally...

Preengraftment Syndrome after Unrelated Cord Blood Transplant Is a Strong Predictor of Acute and Chronic Graft-versus-Host Disease

Biology of Blood and Marrow Transplantation — Tue, 25 Aug 2009 23:00:00 +0100

Preengraftment syndrome (PES) is a known complication following unrelated cord blood transplant (CBT) that has not been well characterized. We sought to determine the incidence and clinical outcome of PES among 326 patients 5 × 107/kg had significantly higher risk of developing PES (P = .02). There were significantly higher rates of grade II-V (P < .001), grade III-IV (P < .001) acute and chronic (P = .002) graft-versus-host disease (aGVHD, cGVHD) in those who developed PES. In a multivariate analysis, PES did not significantly affect overall survival (OS) (P = .38). We conclude that PES is common following CB transplant (CBT) and additional more intensive immune suppression might be considered to decrease the risk of developing aGVHD and cGVHD. (Source: Biology of Blood and Marrow Transp...

Sibling versus Unrelated Donor Allogeneic Hematopoietic Cell Transplantation for Chronic Myelogenous Leukemia: Refined HLA Matching Reveals More Graft-versus-Host Disease but not Less Relapse

Biology of Blood and Marrow Transplantation — Wed, 19 Aug 2009 23:00:00 +0100

Unrelated donor (URD) hematopoietic cell transplantation (HCT) can eradicate chronic myelogenous leukemia (CML). It has been postulated that greater donor–recipient histoincompatibility can augment the graft-versus-leukemia (GVL) effect. We previously reported similar, but not equivalent, outcomes of URD versus sibling donor HCT for CML using an older, less precise classification of HLA matching. Here, we used our recently refined HLA-matching classification, which is suitable for interpretation when complete allele-level typing is unavailable, to reanalyze outcomes of previous HCT for CML. We found that using our new matching criteria identifies substantially more frequent mismatching than older, less precise “6 of 6 antigen–matched” URD-HCT. Under the new criteria, only 37% of th...

Failure to Achieve a Threshold Dose of CD34+CD110+ Progenitor Cells in the Graft Predicts Delayed Platelet Engraftment after Autologous Stem Cell Transplantation for Multiple Myeloma

Biology of Blood and Marrow Transplantation — Wed, 19 Aug 2009 23:00:00 +0100

To predict platelet engraftment more accurately post autologous stem cell transplantation (SCT), we retrospectively analyzed the CD34+CD110+ (CD110 or c-mpl, thrombopoietin receptor) content in the grafts of 70 patients undergoing transplantation for multiple myeloma (MM) with an in-house flow cytometric assay. We found that infusing at least 3.0 × 104 CD34+CD110+ cells/kg clearly separated the cohort into those who achieved platelet engraftment before or after 21 days. This early megakaryocyte cell marker correlated more closely with early versus delayed platelet engraftment than CD34+ measurements. Of the 70 patients, 4 required ≥ 21 days to achieve platelet transfusion independence. Three of the 4 received a CD34+CD110+ cell dose of 3.0 × 104 CD34+CD110+ cells/kg achieved platelet t...

Sequential Intensified Conditioning and Tapering of Prophylactic Immunosuppressants for Graft-versus-Host Disease in Allogeneic Hematopoietic Stem Cell Transplantation for Refractory Leukemia

Biology of Blood and Marrow Transplantation — Wed, 19 Aug 2009 23:00:00 +0100

For patients with advanced leukemia undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT), a major obstacle to success, especially in those with a high leukemia cell burden, is relapse of the underlying disease. To improve the outcome of allo-HSCT for refractory leukemia, we investigated the strategy of sequential intensified conditioning and early rapid tapering of prophylactic immunosupressants therapy for graft-versus-host disease (GVHD) during the early stage after transplantation. A total of 51 patients with refractory leukemia (median age, 30.0 years; unfavorable karyotypes, 49%) received fludarabine (Flu) 30 mg/m2/day and cytarabine 2 g/m2/day (on days −10 to −6), 4.5 Gy total body irradiation (TBI)/day (on days −5 and −4), and cyclophosphamide (Cy) 60 mg...

Interferon Gamma 13-CA-Repeat Homozygous Genotype and a Low Proportion of CD4+ Lymphocytes Are Independent Risk Factors for Cytomegalovirus Reactivation with a High Number of Copies in Hematopoietic Stem Cell Transplantation Recipients

Biology of Blood and Marrow Transplantation — Sun, 09 Aug 2009 23:00:00 +0100

Cytomegalovirus (CMV) reactivation was analyzed in 92 recipients of allogeneic hematopoietic stem cell transplantation (HSCT) in relation to the proportion of CD4+ lymphocytes in blood and a microsatellite polymorphism within the first intron of the interferon-gamma (IFNG) gene. CMV reactivation was found in 50% of the HSCT recipients; in 30% of these individuals, the level of CMV copies exceeded 100 per 105 peripheral blood (PB) cells on at least one occasion during the 100-day post-HSCT observation period. This high CMV copy level was most frequently found between 31 and 60 days post-HSCT (P = .021). Patients with ≥ 100 CMV copies/105 cells were characterized by poorer overall survival (OS) compared with those lacking CMV copies or having < 100 CMV copies/105 cells (P = .04), and they ...

Osteochondroma after Hematopoietic Stem Cell Transplantation in Childhood. An Italian Study on Behalf of the AIEOP-HSCT Group

Biology of Blood and Marrow Transplantation — Sun, 09 Aug 2009 23:00:00 +0100

A retrospective study was conducted among Italian children treated with hematopoietic stem cell transplant (HSCT) to evaluate the incidence and risk factors in the development of osteochondroma (OC). OC occurred in 27 patients who received autologous or allogeneic HSCT. The estimated 5-, 10-, and 15-year cumulative risk of developing OC was 0.5%, 3.2%, and 6.1%, respectively. Analysis of cumulative risk stratified by the various risk factors revealed that male sex (P=.026), autologous HSCT (P=.001), age at HSCT (≤3 years) (P < .0001), and total body irradiation (TBI) (P (Source: Biology of Blood and Marrow Transplantation)

Biology of Blood and Marrow Transplantation — Thu, 06 Aug 2009 11:05:31 +0100

(Source: Biology of Blood and Marrow Transplantation)

Officers and Directors of ASBMT

Biology of Blood and Marrow Transplantation — Thu, 06 Aug 2009 11:05:31 +0100

(Source: Biology of Blood and Marrow Transplantation)

Editorial Board

Biology of Blood and Marrow Transplantation — Thu, 06 Aug 2009 11:05:31 +0100

(Source: Biology of Blood and Marrow Transplantation)

Masthead

Biology of Blood and Marrow Transplantation — Thu, 06 Aug 2009 11:05:31 +0100

(Source: Biology of Blood and Marrow Transplantation)

Biology of Blood and Marrow Transplantation via MedWorm.com

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Masthead (Purpose and Scope)

Erratum

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Antifungal Management

Response to Letter from Demetrios S. Theodoropoulos, MD, DSc

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Masthead (Purpose and Scope)

Falling Chimerism after Reduced Intensity Conditioning Transplantation

The Role of Cytotoxic Therapy with Hematopoietic Stem Cell Transplantation in the Treatment of Follicular Lymphoma: An Evidence-Based Review

Challenges in Hematopoietic Stem Cell Transplantation

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Expansion of NKG2A−LIR1− Natural Killer Cells in HLA-Matched, Killer Cell Immunoglobulin-Like Receptors/HLA-Ligand Mismatched Patients following Hematopoietic Cell Transplantation

Chemokine Receptor CCR5 Mediates AlloImmune Responses in Graft-versus-Host Disease

Erratum

Allogeneic Stem Cell Transplantation for Myelofibrosis with Leukemic Transformation

Gain of 1q21 Is an Unfavorable Genetic Prognostic Factor for Multiple Myeloma Patients Treated with High-Dose Chemotherapy

Early Elevation of C-Reactive Protein Correlates with Severe Infection and Nonrelapse Mortality in Children Undergoing Allogeneic Stem Cell Transplantation

Allogeneic Hematopoietic Cell Transplant for Prolymphocytic Leukemia

Improved Survival with Inhibitory Killer Immunoglobulin Receptor (KIR) Gene Mismatches and KIR Haplotype B Donors after Nonmyeloablative, HLA-Haploidentical Bone Marrow Transplantation

High-Dose Chemotherapy with Blood or Bone Marrow Transplants for Rhabdomyosarcoma

Hypertension in Long-Term Survivors of Pediatric Hematopoietic Cell Transplantation

Erratum

The Addition of 400 cGY Total Body Irradiation to a Regimen Incorporating Once-Daily Intravenous Busulfan, Fludarabine, and Antithymocyte Globulin Reduces Relapse Without Affecting Nonrelapse Mortality in Acute Myelogenous Leukemia

Cord Blood Units with Low CD34+ Cell Viability Have a Low Probability of Engraftment after Double Unit Transplantation

Poor Mobilization of Hematopoietic Stem Cells—Definitions, Incidence, Risk Factors, and Impact on Outcome of Autologous Transplantation

Nonmyeloablative HLA-Haploidentical Bone Marrow Transplantation with High-Dose Posttransplantation Cyclophosphamide: Effect of HLA Disparity on Outcome

Mycophenolate Pharmacokinetics and Association with Response to Acute Graft-versus-Host Disease Treatment from the Blood and Marrow Transplant Clinical Trials Network

Efficacy of Bone Marrow-Derived Mesenchymal Stem Cells in the Treatment of Sclerodermatous Chronic Graft-versus-Host Disease: Clinical Report

Comparison of Two Pretransplant Predictive Models and a Flexible HCT-CI Using Different Cut off Points to Determine Low-, Intermediate-, and High-Risk Groups: The Flexible HCT-CI Is the Best Predictor of NRM and OS in a Population of Patients Undergoing allo-RIC

Race and Outcomes of Autologous Hematopoietic Cell Transplantation for Multiple Myeloma

Low-Dose Total Body Irradiation and Fludarabine Conditioning for HLA Class I-Mismatched Donor Stem Cell Transplantation and Immunologic Recovery in Patients with Hematologic Malignancies: A Multicenter Trial

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ASBMT News

Blood Stem Cell Transplantation in Older Patients

Reduced Frequency of Regulatory T Cells in Peripheral Blood Stem Cell Compared to Bone Marrow Transplantations

New-Onset Lymphopenia Assessed during Routine Follow-up Is a Risk Factor for Relapse Postautologous Peripheral Blood Hematopoietic Stem Cell Transplantation in Patients with Diffuse Large B-Cell Lymphoma

Outcomes of Hematologic Malignancies after Unrelated Donor Hematopoietic Cell Transplantation According to Place of Residence

Outcome of Transplantation for Myelofibrosis

Rapid, Flow Cytometric Assay for NK Alloreactivity Reveals Exceptions to Rules Governing Alloreactivity

Pre-Engraftment Syndrome after Double-Unit Cord Blood Transplantation: A Distinct Syndrome not Associated with Acute Graft-Versus-Host Disease

The Role of Missing Killer Cell Immunoglobulin-Like Receptor Ligands in T Cell Replete Peripheral Blood Stem Cell Transplantation from HLA-Identical Siblings

Robert Truitt Tribute

Successful Hematopoietic Stem Cell Transplantation in 2 Children with X-Linked Chronic Granulomatous Disease from Their Unaffected HLA-Identical Siblings Selected Using Preimplantation Genetic Diagnosis Combined with HLA Typing

An Age-Dependent Pharmacokinetic Study of Intravenous and Oral Mycophenolate Mofetil in Combination with Tacrolimus for GVHD Prophylaxis in Pediatric Allogeneic Stem Cell Transplantation Recipients

Partial T Cell-Depleted Allogeneic Stem Cell Transplantation following Reduced-Intensity Conditioning Creates a Platform for Immunotherapy with Donor Lymphocyte Infusion and Recipient Dendritic Cell Vaccination in Multiple Myeloma

Monitoring and Preemptive Rituximab Therapy for Epstein-Barr Virus Reactivation after Antithymocyte Globulin Containing Nonmyeloablative Conditioning for Umbilical Cord Blood Transplantation

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Minor ABO-Mismatches are Risk Factors for Acute Graft-versus-Host Disease in Hematopoietic Stem Cell Transplant Patients

Pulmonary, Gonadal, and Central Nervous System Status after Bone Marrow Transplantation for Sickle Cell Disease

The Effect of the Composition of Unrelated Donor Bone Marrow and Peripheral Blood Progenitor Cell Grafts on Transplantation Outcomes

Association of HMGB1 Polymorphisms with Outcome after Allogeneic Hematopoietic Cell Transplantation

Hepatic Veno-Occlusive Disease following Stem Cell Transplantation: Incidence, Clinical Course, and Outcome

Erratum

Iron Overload in Patients Receiving Allogeneic Hematopoietic Stem Cell Transplantation: Quantification of Iron Burden by a Superconducting Quantum Interference Device (SQUID) and Therapeutic Effectiveness of Phlebotomy

Outcome of 125 Children with Chronic Myelogenous Leukemia Who Received Transplants from Unrelated Donors: The Japan Marrow Donor Program

T helper17 Cells Are Sufficient But Not Necessary to Induce Acute Graft-Versus-Host Disease

Critical Situation of Bone Marrow Transplantation: Information Distribution Regarding the Problem of a Shortage of Bone Marrow Filters

Interleukin 17 Is Not Required for Autoimmune-Mediated Pathologic Damage during Chronic Graft-versus-Host Disease

Oral Chronic Graft-versus-Host Disease Scoring Using the NIH Consensus Criteria

Transplantation of Unrelated Donor Umbilical Cord Blood for Nonmalignant Diseases: a Single Institution's Experience with 45 Patients

Hematopoietic Stem Cell Transplantation for Refractory or Recurrent Non-Hodgkin Lymphoma in Children and Adolescents