Biology of Blood and Marrow Transplantation via MedWorm.com

Biology of Blood and Marrow Transplantation — Sat, 14 Jan 2012 07:41:04 +0100

(Source: Biology of Blood and Marrow Transplantation)

Officers and Directors of ASBMT

Biology of Blood and Marrow Transplantation — Sat, 14 Jan 2012 07:41:04 +0100

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Editorial Board

Biology of Blood and Marrow Transplantation — Sat, 14 Jan 2012 07:41:04 +0100

(Source: Biology of Blood and Marrow Transplantation)

Purpose and Scope

Biology of Blood and Marrow Transplantation — Sat, 14 Jan 2012 07:41:04 +0100

(Source: Biology of Blood and Marrow Transplantation)

New Hope for Mobilization Failures . . . Again

Biology of Blood and Marrow Transplantation — Wed, 21 Dec 2011 05:00:00 +0100

Patients undergoing peripheral blood stem cell mobilization for autologous transplantation may fail to achieve the generally accepted minimum threshold for transplantation (≥2 × 106 CD34/kg) despite using optimal doses of granulocyte-colony stimiulating factor (G-CSF) or chemotherapy plus G-CSF. Failure rates vary from center to center but are felt to be highest in certain diseases such as non-Hodgkin’s lymphoma (NHL), Hodgkin’s disease (HD), and in heavily pretreated patients with multiple myeloma (MM). Although there is both vigorous debate and varying understanding of the optimal methods for mobilization (G-CSF alone versus chemotherapy plus G-CSF) there is general agreement that these diseases and various risk factors are associated with high rates of stem cell collection failur...

2012 BMT Tandem Meetings

Biology of Blood and Marrow Transplantation — Fri, 16 Dec 2011 05:00:00 +0100

2012 BMT TANDEM MEETINGS WILL BE FEB. 1-5 IN SAN DIEGO The combined 2012 annual meetings of ASBMT and the Center for International Blood and Marrow Transplant Research (CIBMTR) will be Feb. 1-5 at the Manchester Grand Hyatt in San Diego. (Source: Biology of Blood and Marrow Transplantation)

The National Marrow Donor Program’s Symposium on Hematopoietic Cell Transplantation in 2020: A Health Care Resource and Infrastructure Assessment

Biology of Blood and Marrow Transplantation — Fri, 16 Dec 2011 05:00:00 +0100

This report details the deliberations and recommendations of a national symposium, “Hematopoietic Cell Transplantation in 2020: A Health Care Resource and Infrastructure Assessment,” held in September 2010. (Source: Biology of Blood and Marrow Transplantation)

NCI, NHLBI/PBMTC First International Conference on Late Effects after Pediatric Hematopoietic Cell Transplantation: Health-Related Quality of Life, Functional, and Neurocognitive Outcomes

Biology of Blood and Marrow Transplantation — Mon, 12 Dec 2011 05:00:00 +0100

The purpose of this manuscript is to summarize issues relevant to health-related quality of life (HRQL), physical function, and neurocognitive function for survivors of pediatric hematopoietic stem cell transplantation (HCT). The physiologic and psychological demands of HCT and its sequelae have the potential to substantially alter HRQL. When compared with research on adult HCT recipients, research in pediatric HRQL following HCT has lagged considerably. Initially, this lag was because of limited validated questionnaires, small numbers of affected patients, and a general lack of salience for the topic relative to traditional endpoints, such as transplant-related toxicity and potential mortality. The percentage of childhood HCT survivors with physical disability ranges from 7% to 17% in stu...

My AML Cytogenetics Classification Scheme Is Better Than Yours

Biology of Blood and Marrow Transplantation — Thu, 08 Dec 2011 05:00:00 +0100

Growing up in Rhode Island, my brother and I spent hours – I mean, hours – in the schoolyard around the block from our house arguing over which baseball team was better: the Yankees or the Red Sox. I rooted for the Yankees, just like my father and his father, while my brother, the second born, favored the Sox. This was the late 1970s, and we compared player to player (Jackson vs Rice, Guidry vs Tiant), position to position, tirelessly trying to convince the other, based on the past performance of our teams, which was superior, and each of us leaving the quarrel convinced the other was a complete idiot. (Source: Biology of Blood and Marrow Transplantation)

Biology of Blood and Marrow Transplantation — Thu, 17 Nov 2011 01:34:23 +0100

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Officers and Directors of ASBMT

Biology of Blood and Marrow Transplantation — Thu, 17 Nov 2011 01:34:23 +0100

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Editorial Board

Biology of Blood and Marrow Transplantation — Thu, 17 Nov 2011 01:34:23 +0100

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Masthead (Purpose and Scope)

Biology of Blood and Marrow Transplantation — Thu, 17 Nov 2011 01:34:23 +0100

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A Phase I Study of Gemtuzumab Ozogamicin (GO) in Combination with Busulfan and Cyclophosphamide (Bu/Cy) and Allogeneic Stem Cell Transplantation in Children with Poor-Risk CD33+ AML: A New Targeted Immunochemotherapy Myeloablative Conditioning (MAC) Regimen

Biology of Blood and Marrow Transplantation — Thu, 10 Nov 2011 05:00:00 +0100

Children with high-risk acute myelogenous leukemia (AML) (induction failure [IF], refractory relapse [RR], third complete remission [CR3]) have dismal outcomes. Over 80% of AML patients express CD33, a target of gemtuzumab ozogamicin (GO). GO is an active drug in childhood AML but has not been studied in a myeloablative conditioning regimen. We sought to determine the safety of GO in combination with busulfan/cyclophosphamide (Bu/Cy) conditioning before allogeneic hematopoietic stem cell transplantation (alloSCT). GO was administered on day −14 at doses of 3.0, 4.5, 6.0, and 7.5 mg/m2, busulfan on days −7, −6, −5, −4 (12.8-16.0 mg/kg), and cyclophosphamide on days −3 and −2 (60 mg/kg/day). GVHD prophylaxis consisted of tacrolimus and mycophenolate mofetil. We enrolled 12 pati...

Dasatinib as Salvage Therapy for Steroid Refractory and Imatinib Resistant or Intolerant Sclerotic Chronic Graft-versus-Host Disease

Biology of Blood and Marrow Transplantation — Mon, 07 Nov 2011 05:00:00 +0100

We present here the first direct clinical evidence, from 3 patients treated in a small single-center series, suggesting that dasatinib can be a therapeutic option for patients with severe scGVHD resistant or intolerant to imatinib. All patients achieved partial response, with improvement in scGHVD target organs severity, joint mobility, lung impairment, and deep fibrotic lesions. This clinical response has remained stable or continued to improve after a median of 22 months (20-25) on dasatinib treatment, with very good tolerance. In addition, corticosteroids could be discontinued or significantly reduced in all patients. This clinical evidence suggests that dasatinib could be a safe and effective alternative for scGVHD patients refractory to corticosteroids and resistant or intolerant to i...

Biology of Blood and Marrow Transplantation — Wed, 26 Oct 2011 21:52:17 +0100

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Officers and Directors of ASBMT

Biology of Blood and Marrow Transplantation — Wed, 26 Oct 2011 21:52:17 +0100

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Editorial Board

Biology of Blood and Marrow Transplantation — Wed, 26 Oct 2011 21:52:17 +0100

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Masthead

Biology of Blood and Marrow Transplantation — Wed, 26 Oct 2011 21:52:17 +0100

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Comorbidities and Outcomes: Advancing the Field Comes at a Price

Biology of Blood and Marrow Transplantation — Tue, 25 Oct 2011 04:00:00 +0100

In this issue of Biology of Blood and Marrow Transplantation, colleagues from Dresden, Germany, reported on the prognostic impact of the hematopoietic cell transplantation-specific comorbidity index (HCT-CI) among patients diagnosed with acute myeloid leukemia and treated with allogeneic hematopoietic cell transplantation (HCT) using at least 9 different types of conditioning regimens. The authors elected to stratify patients into HCT-CI scores of 0 (5%), 1-2 (21%), and ≥3 (74%). Multiple analyses failed to show any statistically significant association between the HCT-CI scores and nonrelapse mortality (NRM) or overall survival (OS) . (Source: Biology of Blood and Marrow Transplantation)

The Pretransplantation Serum Cytokine Profile in Allogeneic Stem Cell Recipients Differs from Healthy Individuals, and Various Profiles are Associated with Different Risks of Posttransplantation Complications

Biology of Blood and Marrow Transplantation — Fri, 21 Oct 2011 04:00:00 +0100

Cytokines play a key role in regulation of normal and malignant hematopoiesis, angiogenesis, and inflammation. Serum levels of several cytokines are altered in patients with hematologic malignancies, and pretransplant cytokine levels seem to have a prognostic impact in patients treated with allogeneic stem cell transplantation. However, the cytokine system constitutes an interacting functional network, and it may therefore be more relevant to look at serum cytokine profiles rather than the serum levels of single cytokines in allotransplanted patients. We therefore investigated the pretransplantation serum levels of 35 cytokines in a group of 44 consecutive allogeneic stem cell transplantation patients, mainly with a primary diagnosis of acute leukemia. Serum samples were collected before t...

Identification of a Coordinated CD8 and CD4 T Cell Response Directed Against Mismatched HLA Class I Causing Severe Acute Graft-versus-Host Disease

Biology of Blood and Marrow Transplantation — Wed, 19 Oct 2011 04:00:00 +0100

In this study we investigated whether a coordinated response of CD8 and CD4 T cells could be demonstrated in an HLA class I–directed immune response in a patient who developed severe graft-versus-host disease (GVHD) after the administration HLA-A2–mismatched donor lymphocyte infusion in the absence of inflammatory conditions. A previously administered donor lymphocyte infusion from the same donor did not lead to an immune response, excluding the presence of a substantial pool of CD8 T cells cross-reactive against HLA-A2 within the memory T cell compartment of the donor. Analysis of isolated donor CD8 and CD4 T cell clones activated during the GVHD revealed a polyclonal CD8 T cell response directed against the mismatched HLA-A2 and a polyclonal CD4 T cell response recognizing HLA-A2–...

T Cell and B Cell Immunity can be Reconstituted with Mismatched Hematopoietic Stem Cell Transplantation Without Alkylator Therapy in Artemis-Deficient Mice Using Anti-Natural Killer Cell Antibody and Photochemically Treated Sensitized Donor T Cells

Biology of Blood and Marrow Transplantation — Wed, 19 Oct 2011 04:00:00 +0100

Children with Artemis-deficient T−B−NK+ severe combined immunodeficiency are at high risk for graft rejection from natural killer (NK) cells and toxicity from increased sensitivity to the alkylating agents used in mismatched hematopoietic stem cell transplantation (HSCT). We evaluated the use of a nonalkylating agent regimen before HSCT in Artemis-deficient (mArt−/−) C57Bl/6 (B6) mice to open marrow niches and achieve long-term multilineage engraftment with full T cell and B cell immune reconstitution. We found that partial depletion of both recipient NK cells using anti-NK1.1 monoclonal antibody and donor T cells sensitized to recipient splenocytes was necessary. BALB/c-sensitized T cells (STCs) were photochemically treated (PCT) with psoralen and UVA light to inhibit proliferatio...

Age and the Outcome of Allogeneic Hematopoietic Stem Cell Transplantation: Was Tacitus Wrong?

Biology of Blood and Marrow Transplantation — Mon, 17 Oct 2011 04:00:00 +0100

As a fellow training in allogeneic bone marrow transplantation in the early 1990s, I learned what Tacitus apparently appreciated almost 2 millennia before me: corpora lente augescent cito extinguuntur (bodies grow slowly and die quickly). I was therefore excited to see that older bodies apparently tolerate the rigors of myeloablative allogeneic hematopoietic stem cell transplantation (HSCT) just like younger ones . (Source: Biology of Blood and Marrow Transplantation)

NCI, NHLBI/PBMTC First International Conference on Late Effects after Pediatric Hematopoietic Cell Transplantation: Endocrine Challenges—Thyroid Dysfunction, Growth Impairment, Bone Health, & Reproductive Risks

Biology of Blood and Marrow Transplantation — Mon, 17 Oct 2011 04:00:00 +0100

The endocrine system is highly susceptible to damage by high-dose chemotherapy and/or irradiation before hematopoietic cell transplantation (HCT) during childhood. The specific endocrine organs most affected by HCT include the thyroid gland, the pituitary, and the gonads. In addition, hormones that support development and stability of the skeletal system are also affected. Insufficiency of thyroid hormone is 1 of the most common late sequelae of HCT, and occurs more often in young children. Deficiency in the pituitary’s production of growth hormone is a problem of unique concern to the pediatric population. The reproductive risks of HCT depend on the patient’s gender and pubertal status at the time of HCT. Pubertal or gonadal failure frequently occurs, especially in females. Infertilit...

Reduced-Intensity Allogeneic Hematopoietic Transplantation Should Be Considered a Standard of Care for Older Patients with Acute Myeloid Leukemia

Biology of Blood and Marrow Transplantation — Mon, 17 Oct 2011 04:00:00 +0100

Acute myeloid leukemia (AML) is primarily a disease of older people with a median age greater than 65 years. The treatment of AML in elderly patients remains a major challenge. Older patients are more likely to have high-risk cytogenetic abnormalities, and age itself confers a poor prognosis. There has been little progress with standard forms of chemotherapy . (Source: Biology of Blood and Marrow Transplantation)

Plerixafor for Autologous Peripheral Blood Stem Cell Mobilization in Patients Previously Treated with Fludarabine or Lenalidomide

Biology of Blood and Marrow Transplantation — Fri, 14 Oct 2011 04:00:00 +0100

In conclusion, salvage mobilization with plerixafor plus G-CSF is successful in the majority of patients with MM previously treated with lenalidomide. In fludarabine-exposed patients, only 58% of patients will achieve successful salvage mobilization with plerixafor plus G-CSF, suggesting the need for novel mobilization regimens algorithms in this subgroup of patients. (Source: Biology of Blood and Marrow Transplantation)

National Cancer Institute–National Heart, Lung and Blood Institute/Pediatric Blood and Marrow Transplant Consortium First International Consensus Conference on Late Effects After Pediatric Hematopoietic Cell Transplantation: Long-Term Organ Damage and Dysfunction

Biology of Blood and Marrow Transplantation — Mon, 03 Oct 2011 04:00:00 +0100

This article describes our current understanding of the pathophysiology of late effects involving the gastrointestinal, renal, cardiac, and pulmonary systems, and discusses post-HCT metabolic syndrome studies. Underlying diseases, pretransplantation exposures, transplantation conditioning regimens, graft-versus-host disease, and other treatments contribute to these problems. Because organ systems are interdependent, long-term complications with similar pathophysiologic mechanisms often involve multiple organ systems. Current data suggest that post-HCT organ complications result from cellular damage that leads to a cascade of complex events. The interplay between inflammatory processes and dysregulated cellular repair likely contributes to end-organ fibrosis and dysfunction. Although many l...

Biology of Blood and Marrow Transplantation — Thu, 22 Sep 2011 11:25:10 +0100

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Officers and Directors of ASBMT

Biology of Blood and Marrow Transplantation — Thu, 22 Sep 2011 11:25:10 +0100

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Editorial Board

Biology of Blood and Marrow Transplantation — Thu, 22 Sep 2011 11:25:10 +0100

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Masthead (Purpose and Scope)

Biology of Blood and Marrow Transplantation — Thu, 22 Sep 2011 11:25:10 +0100

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Hydrodynamic Delivery of Human IL-15 cDNA Increases Murine Natural Killer Cell Recovery after Syngeneic Bone Marrow Transplantation

Biology of Blood and Marrow Transplantation — Thu, 08 Sep 2011 04:00:00 +0100

Immune deficiency immediately following bone marrow transplantation (BMT) increases susceptibility to opportunistic infections as well as tumor relapse. Natural Killer (NK) cells play important roles in the resistance to virally infected and transformed cells. Interleukin (IL)-15 has been shown to be essential for NK cell development and survival. We administered human (h) IL-15 cDNA (pIL-15) via hydrodynamic delivery to murine recipients undergoing congenic BMT to determine its effects on NK cell reconstitution. Hydrodynamic pIL-15 delivery resulted in high levels of hIL-15 protein in the serum that lasted for several days and then quickly declined. The appearance of hIL-15 was followed by a significant increase of mature donor-derived NK cells within the bone marrow, spleens, and livers ...

CIK: A Path to GVL without GVHD?

Biology of Blood and Marrow Transplantation — Thu, 08 Sep 2011 04:00:00 +0100

In allogeneic hematopoietic cell transplantation (HCT), the benefit of graft-versus-leukemia (GVL) effects often comes with the harm of graft-versus-host disease (GVHD). In this issue of BBMT, Laport et al. map a possible path toward GVL with a reduced risk of GVHD. (Source: Biology of Blood and Marrow Transplantation)

Host Basophils Are Dispensable for Induction of Donor T Helper 2 Cell Differentiation and Severity of Experimental Graft-versus-Host Disease

Biology of Blood and Marrow Transplantation — Fri, 26 Aug 2011 04:00:00 +0100

Host hematopoietic-derived antigen-presenting cells are important for induction of graft-versus-host disease (GVHD). The relative importance of various subsets of hematopoietic-derived antigen-presenting cells is not well understood. Recent data suggest that basophils can function as antigen-presenting cells and induce T helper 2 (Th2) lymphocyte responses. We investigated the role of host basophils in the induction of donor T cell responses and GVHD after allogeneic bone marrow transplantation. Elimination of host basophils did not alter the severity of GVHD-induced mortality across multiple clinically relevant models of allogeneic bone marrow transplantation. Furthermore, induction of donor T cell proliferation and Th2 polarization was not altered significantly after depletion of host b...

Dynamics of Cytomegalovirus (CMV) Plasma DNAemia in Initial and Recurrent Episodes of Active CMV Infection in the Allogeneic Stem Cell Transplantation Setting: Implications for Designing Preemptive Antiviral Therapy Strategies

Biology of Blood and Marrow Transplantation — Thu, 25 Aug 2011 04:00:00 +0100

Preemptive antiviral therapy strategies for active cytomegalovirus (CMV) infection occurring in allogeneic stem cell transplant recipients should be optimized to avoid overtreatment. The current study was aimed at determining whether the analysis of the kinetics of CMV DNA load in plasma may provide useful information for the therapeutic management of active CMV infection in this setting. A total of 59 consecutive patients were included in the study, of which 40 (67.8%) developed 1 (n = 21) or more (n = 19) episodes of CMV DNAemia. The need for antiviral therapy for initial or secondary episodes of CMV DNAemia could not be predicted on the basis of the CMV DNA load value in the first plasma testing positive by polymerase chain reaction (PCR). In contrast, in the absence of antiviral thera...

Biology of Blood and Marrow Transplantation — Tue, 16 Aug 2011 23:40:11 +0100

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Officers and Directors of ASBMT

Biology of Blood and Marrow Transplantation — Tue, 16 Aug 2011 23:40:11 +0100

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Editorial Board

Biology of Blood and Marrow Transplantation — Tue, 16 Aug 2011 23:40:11 +0100

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Masthead (Purpose and Scope)

Biology of Blood and Marrow Transplantation — Tue, 16 Aug 2011 23:40:11 +0100

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Stable Long-Term Pulmonary Function after Myeloablative Double Cord Blood Transplant

Biology of Blood and Marrow Transplantation — Tue, 16 Aug 2011 04:00:00 +0100

Pulmonary dysfunction has been well described after myeloablative transplantation with conventional allogeneic donors; however, whether the risk is similar after alternative donor transplantation with cord blood as the stem cell source has not yet been investigated. We performed a retrospective analysis of patients who underwent double cord blood transplantation after myeloablative conditioning. Pulmonary function tests were performed pretransplantation and at day 80, 1 year, and 2 years posttransplantation, with 56 patients included in the final analysis. No significant change from baseline with respect to the mean values and mean change in pulmonary function test values were observed at 1 year posttransplantation. The rate of lung function decline from baseline to 1 year posttransplantat...

“Pet Negativity”—The New Goal of Cytoreductive Therapy in Hodgkin's Lymphoma?

Biology of Blood and Marrow Transplantation — Tue, 16 Aug 2011 04:00:00 +0100

Functional imaging with [18F] fluorodeoxyglucose-positron emission tomography (FDG-PET) is emerging as a useful technique in the management of patients with Hodgkin's lymphoma (HL). In addition to its use as a staging modality, there is increasing evidence for its role as a prognostic and predictive tool in patients undergoing first-line therapy for this disease . (Source: Biology of Blood and Marrow Transplantation)

Preparative Regimens and Ageism

Biology of Blood and Marrow Transplantation — Fri, 12 Aug 2011 04:00:00 +0100

In this issue of Biology of Blood and Marrow Transplantation Alatrash and colleagues publish the results of allogeneic hematopoietic cell transplantation in 79 patients with acute myeloid leukemia or myelodysplasia age 55 to 76 (median = 58 years) using a conditioning regimen of intravenous fludarabine (40 mg/m2) and busulfan (130 mg/m2) (FLU/BU) each daily from day −6 through day −3, with graft-vs-host disease prophylaxis of tacrolimus and methotrexate (plus antithymocyte globulin with unrelated donors) . The results are quite reasonable with a 2-year event-free survival of 44% for the entire group, and an event-free survival of 68% for those transplanted in first complete remission, 42% for second complete remission, and 30% for those with active disease. The authors conclude that f...

The Doorstep to the Temple of Wisdom

Biology of Blood and Marrow Transplantation — Fri, 12 Aug 2011 04:00:00 +0100

“The doorstep to the temple of wisdom is knowledge of our own ignorance.” Benjamin Franklin. In this issue, Pidala and colleagues report the appalling state of ignorance and confusion regarding withdraw of immunosuppression (IS) after allogeneic hematopoietic stem cell transplantation (allo HCT) . The authors document marked variation practice (even within the same transplant group), high estimates of graft-vs-host disease (GVHD) emerging in the setting of IS taper, and limited confidence of transplant physicians in their therapeutic decisions. The egress from the temple of stem cell transplant is indeed a jumbled muddle. (Source: Biology of Blood and Marrow Transplantation)

Classifying Cytogenetics in Patients with Acute Myelogenous Leukemia in Complete Remission Undergoing Allogeneic Transplantation: A Center for International Blood and Marrow Transplant Research Study

Biology of Blood and Marrow Transplantation — Tue, 02 Aug 2011 04:00:00 +0100

Cytogenetics play a major role in determining the prognosis of patients with acute myelogenous leukemia (AML). However, existing cytogenetics classifications were developed in chemotherapy-treated patients and might not be optimal for patients undergoing allogeneic hematopoietic cell transplantation (HCT). We studied 821 adult patients reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) who underwent HCT for AML in first or second complete remission between 1999 and 2004. We compared the ability of the 6 existing classifications to stratify patients by overall survival. We then defined a new scheme specifically applicable to patients undergoing HCT using this patient cohort. Under this scheme, inv(16) is favorable, a complex karyotype (4 or more abnormali...

Easy-to-Read Informed Consent Forms for Hematopoietic Cell Transplantation Clinical Trials

Biology of Blood and Marrow Transplantation — Mon, 01 Aug 2011 04:00:00 +0100

Informed consent is essential to ethical research and is requisite to participation in clinical research. Yet most hematopoietic cell transplantation (HCT) informed consent forms (ICFs) are written at reading levels that are above the ability of the average person in the United States (U.S.). The recent development of ICF templates by the National Cancer Institute, National Institutes of Health, and the National Heart Blood and Lung Institute have not resulted in increased patient comprehension of information. Barriers to creating Easy-to-Read ICFs that meet U.S. federal requirements and pass institutional review board (IRB) review are the result of multiple interconnected factors. The Blood and Marrow Transplant Clinical Trials Network (BMT CTN) formed an ad hoc review team to address con...

Decreased Serum Albumin as a Biomarker for Severe Acute Graft-versus-Host Disease after Reduced-Intensity Allogeneic Hematopoietic Cell Transplantation

Biology of Blood and Marrow Transplantation — Mon, 01 Aug 2011 04:00:00 +0100

Biomarkers capable of predicting the onset and severity of acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic cell transplantation (HCT) would enable preemptive and risk-stratified therapy. Severe aGVHD leads to gastrointestinal protein loss, resulting in hypoalbuminemia. We hypothesized that decreases in serum albumin at onset of aGVHD would predict the risk of progression to severe aGVHD. We identified 401 patients who developed aGVHD grades II-IV after reduced-intensity allogeneic HCT and reviewed all available serum albumin values from 30 days before HCT to 45 days after initiation of treatment for aGVHD. A ≥0.5 g/dL decrease in serum albumin concentration from pretransplantation baseline to the onset of treatment for aGVHD predicted the subsequent development of ...

Development and Validation of a Test Dose Strategy for Once-Daily i.v. Busulfan: Importance of Fixed Infusion Rate Dosing

Biology of Blood and Marrow Transplantation — Thu, 28 Jul 2011 04:00:00 +0100

We describe sequential studies to achieve accurate prediction of treatment doses of Bu based on the kinetics of a smaller test dose. A total of 335 patients with hematologic malignancies were given daily i.v. Bu 3.2 mg/kg × 4 and fludarabine 50 mg/m2 × 5. Pharmacokinetic monitoring was conducted for both the test dose and first treatment dose of Bu (day −5). Three different test dose schedules were evaluated: 12 mg Bu administered over 20 minutes, 0.8 mg/kg over 3 hours, and 0.8 mg/kg infused at 80 mg/h. The 3.2 mg/kg treatment doses were infused over a fixed time of 3 hours for the first 2 test dose trials and at a fixed rate of 80 mg/h for the final protocol. All test dose infusions were on day −7. In the first 2 schedules, Bu administered over a fixed time had significantly highe...

Plerixafor Added to Chemotherapy Plus G-CSF Is Safe and Allows Adequate PBSC Collection in Predicted Poor Mobilizer Patients with Multiple Myeloma or Lymphoma

Biology of Blood and Marrow Transplantation — Tue, 26 Jul 2011 04:00:00 +0100

We evaluated the safety and efficacy of plerixafor, subsequent to disease-specific chemotherapy followed by granulocyte-colony stimulating factor (G-CSF), in 37 multiple myeloma (MM) or lymphoma patients, who were candidates for autologous stem cell transplantation (ASCT) predicted as poor mobilizers (PMs). Patients were identified as predicted PMs according to the history of a previously failed mobilization attempt or the presence of ≥1 factors predicting an unsuccessful harvest, such as advanced disease, prior extensive radiotherapy, or prolonged treatment, with stem cell poisons, advanced age, or extensive bone marrow involvement. Plerixafor (0.24 mg/kg) was administered subcutaneously for up to 3 consecutive days while continuing G-CSF for 9 to 11 hours before the planned apheresis. ...

Reduced-Intensity Conditioning before Allogeneic Hematopoietic Stem Cell Transplantation in Patients Over 60 Years: A Report from the SFGM-TC

Biology of Blood and Marrow Transplantation — Thu, 21 Jul 2011 04:00:00 +0100

This retrospective multicenter report assessed the outcome of 600 patients with hematologic diseases older than 60 years who received reduced-intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (allo-HSCT), with the specific aim to compare outcomes of patients between 60 and 65 years old (N = 493) with those older than 65 years (N = 107). Except for donor age, there were no significant differences between the groups regarding patients, diseases, and allo-HSCT characteristics. At time of RIC allo-HSCT, 276 patients (46%) were in complete remission. With a median follow-up of 22.8 and 23.7 months in the younger and the older groups, respectively, 2-year relapse, nonrelapse mortality, disease-free survival, and overall survival rates were similar in both groups (2...

Genome-wide Profiling in AML Patients Relapsing after Allogeneic Hematopoietic Cell Transplantation

Biology of Blood and Marrow Transplantation — Thu, 21 Jul 2011 04:00:00 +0100

Molecular pathogenesis of relapse after allogeneic hematopoietic cell transplantation is poorly understood. Data regarding relapse mechanisms after transplantation is scarcely available. We investigated genomic aberrations (GAs) in 21 patients undergoing related and unrelated HLA-matched transplantation in leukemic blasts before transplant and at relapse after transplantation. We found a higher number of GAs after transplantation, suggesting increased genomic instability during relapse. Two of 21 patients showed a large homozygous region spanning the whole HLA-locus on chromosome 6p in the relapse sample. In both patients sequence-based HLA typing of the blasts revealed a loss of the patient-specific allele at the mismatched locus leading to homozygosity for the HLA haplotype shared by the...

Biology of Blood and Marrow Transplantation — Wed, 20 Jul 2011 18:41:27 +0100

(Source: Biology of Blood and Marrow Transplantation)

Officers and Directors of ASBMT

Biology of Blood and Marrow Transplantation — Wed, 20 Jul 2011 18:41:26 +0100

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Editorial Board

Biology of Blood and Marrow Transplantation — Wed, 20 Jul 2011 18:41:26 +0100

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Masthead (Purpose and Scope)

Biology of Blood and Marrow Transplantation — Wed, 20 Jul 2011 18:41:26 +0100

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Treatment of FLT3-ITD-Positive Acute Myeloid Leukemia Relapsing after Allogeneic Stem Cell Transplantation with Sorafenib

Biology of Blood and Marrow Transplantation — Mon, 18 Jul 2011 04:00:00 +0100

Patients with acute myeloid leukemia (AML) and internal tandem duplication of FMS-like tyrosine kinase receptor-3 gene (FLT3-ITD) mutation have poor prognoses and are often treated with allogeneic hematopoietic stem cell transplantation (HSCT). Sorafenib, an inhibitor of multiple kinases including FLT3, has shown promising activity in FLT3-ITD-positive AML. We treated 16 patients with FLT3-ITD-positive AML who relapsed after HSCT with sorafenib alone (n = 8) or in combination with cytotoxic chemotherapy (n = 8). The number of circulating blasts decreased in 80% of cases, but none of the patients achieved complete remission (CR); 3 achieved partial remission. Two patients were bridged to a second transplantation but both relapsed within 3 months of the transplantation. Median overall surviv...

Donor Characteristics Affecting Graft Failure, Graft-versus-Host Disease, and Survival after Unrelated Donor Transplantation with Reduced-Intensity Conditioning for Hematologic Malignancies

Biology of Blood and Marrow Transplantation — Mon, 18 Jul 2011 04:00:00 +0100

We examined the effect of donor characteristics on graft failure (95% donor chimerism, 145 patients were 5% to 95%, and 63 patients were (Source: Biology of Blood and Marrow Transplantation)

Evaluation and Management of BK Virus-Associated Nephropathy Following Allogeneic Hematopoietic Cell Transplantation

Biology of Blood and Marrow Transplantation — Mon, 18 Jul 2011 04:00:00 +0100

BK virus nephropathy is a common cause of graft loss in kidney transplant recipients. Cases of BK nephropathy following allogeneic hematopoietic cell transplantation (HCT) are underreported. An increased incidence of BK virus-associated nephropathy is being seen in the setting of more profound and prolonged immunosuppression following solid organ transplantation and HCT. We will review diagnostic and treatment modalities for BK-associated nephropathy following allogeneic HCT. (Source: Biology of Blood and Marrow Transplantation)

Hematopoietic Stem Cells Survive Circulation Arrest and Reconstitute Hematopoiesis in Myeloablated Mice

Biology of Blood and Marrow Transplantation — Sun, 17 Jul 2011 23:00:00 +0100

Hematopoietic stem and progenitor cells (HSPC) for bone marrow transplantation are currently obtained directly from living voluntary donors or from cord blood units. However, a suitable donor is not always found. Because HSPC are known for their relative resistance to hypoxia, using an experimental murine model, we explored cadaveric bone marrow (BM) as their alternative source. After donor mice were sacrificed, BM was left in intact femurs at 37°C, 20°C, or 4°C under ischemic conditions, resulting in combined oxygen and metabolic substrate shortage and the accumulation of metabolic waste products. BM cells were harvested after a set time period ranging from 0 to 48 hours. To determine the impact of delayed harvesting on the transplantability of HSPC, a competitive repopulation assay us...

Polymorphisms in CCR6 Are Associated with Chronic Graft-versus-Host Disease and Invasive Fungal Disease in Matched-Related Hematopoietic Stem Cell Transplantation

Biology of Blood and Marrow Transplantation — Fri, 15 Jul 2011 04:00:00 +0100

This study shows that CCR6 SNPs can be used to predict clinical outcome, and that polymorphisms in the CCR6 gene may influence T cell–mediated immune reactions after HSCT. (Source: Biology of Blood and Marrow Transplantation)

NCI, NHLBI First International Consensus Conference on Late Effects after Pediatric Hematopoietic Cell Transplantation: Etiology and Pathogenesis of Late Effects after HCT Performed in Childhood—Methodologic Challenges

Biology of Blood and Marrow Transplantation — Fri, 15 Jul 2011 04:00:00 +0100

Hematopoietic cell transplantation (HCT) is now a curative option for certain categories of patients with hematologic malignancies and other life-threatening illnesses. Technical and supportive care has resulted in survival rates that exceed 70% for those who survive the first 2 years after HCT. However, long-term survivors carry a high burden of morbidity, including endocrinopathies, musculoskeletal disorders, cardiopulmonary compromise, and subsequent malignancies. Understanding the etiologic pathways that lead to specific post-HCT morbidities is critical to developing targeted prevention and intervention strategies. Understanding the molecular underpinnings associated with graft-versus-host disease (GVHD), organ toxicity, relapse, opportunistic infection, and other long-term complicatio...

Genetic Variations in the Mycophenolate Mofetil Target Enzyme Are Associated with Acute GVHD Risk after Related and Unrelated Hematopoietic Cell Transplantation

Biology of Blood and Marrow Transplantation — Mon, 11 Jul 2011 04:00:00 +0100

The objective of this study was to identify the impact of IMPDH1 gene polymorphisms on the outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Four IMPDH1 gene SNPs (IVS7 +125 G>A, IVS8-106 G>A, exon15 1572 G>A, and 5′ flanking intron-exon region C>T) were analyzed in 240 consecutive pairs of transplant recipients and their donors. The presence of the IMPDH1 IVS8−106 G/G genotype in recipients was associated with a significantly higher incidence of acute graft-versus-host disease (aGVHD) than other genotypes, in both unrelated and sibling transplantation cohorts (unrelated cohort: 83.3% vs 63.9%, P = .048; sibling cohort: 47.6% vs 17.3%, P = .008). Multivariate analysis confirmed that recipients with the IVS8−106 G/G genotype were at significantly higher risk ...

Double Reduced-Intensity Allogeneic Hematopoietic Stem Cell Transplantation: A Retrospective Study from the SFGM-TC

Biology of Blood and Marrow Transplantation — Mon, 11 Jul 2011 04:00:00 +0100

The purpose of this paper is to describe the outcome of patients who underwent double allogeneic hematopoietic stem cell transplantation (AHSCT) with reduced-intensity conditioning regimens (RIC). Forty-five patients who received double RIC-AHSCT between 1997 and 2006 were retrospectively studied. The predominant diagnosis was acute myeloid leukemia (AML) (n = 17). Other diagnoses were aplasic anemia (AA) (n = 5), myelodysplasic disorder (n = 5), acute lymphoblastic leukemia (ALL) (n = 4), chronic myelomonocytic leukemia (CML) (n = 3), myeloma (n = 3), non-Hodgkin lymphoma (NHL) (n = 3), chronic lymphocytic leukemia (CLL) (n = 2), Hodgkin's disease (HD) (n = 2), and chronic myelomonocytic leukemia (n = 1). Main indications for RIC-AHSCT 2 were relapse (n = 25, 56%) and early (n = 8, 18%) o...

Tocilizumab for the Treatment of Steroid Refractory Graft-versus-Host Disease

Biology of Blood and Marrow Transplantation — Mon, 11 Jul 2011 04:00:00 +0100

In this study, we report our experience with the administration of tocilizumab, an anti-interleukin 6 receptor antibody, in the treatment of steroid refractory GVHD. Tocilizumab was administered to 8 patients with refractory acute (n = 6) or chronic GVHD (cGVHD) (n = 2) once every 3 to 4 weeks. The majority of patients with acute GVHD (aGVHD) had grade IV organ involvement of the skin or gastrointestinal tract, whereas both patients with cGVHD had long-standing severe skin sclerosis at the time of treatment. There were no allergic or infusion-related adverse events. Treatment was discontinued in one patient over concerns that tocilizumab may have worsened preexisting hyperbilirubinemia. Several patients also had transient elevations in serum transaminase values. Infections were the primary...

Can G-CSF Cause Leukemia in Hematopoietic Stem Cell Donors?

Biology of Blood and Marrow Transplantation — Mon, 11 Jul 2011 04:00:00 +0100

A large majority of allogeneic hematopoietic stem cell donations are achieved using granulocyte-colony stimulating factor (G-CSF). G-CSF use has been associated with later development of myelodysplastic syndromes/acute myelogenous leukemia (MDS/AML) in several clinical circumstances. Although clinical data to date have failed to identify any increased incidence of MDS/AML in G-CSF mobilized donors, the quality of these data are insufficient to exclude a long-term risk. Physicians should explain the potential risk to donors, and where appropriate, offer donors the option of marrow donation. (Source: Biology of Blood and Marrow Transplantation)

Accurate Targeting of Daily Intravenous Busulfan with 8-Hour Blood Sampling in Hospitalized Adult Hematopoietic Cell Transplant Recipients

Biology of Blood and Marrow Transplantation — Wed, 06 Jul 2011 04:00:00 +0100

In this report, we describe our experiences with TDM of daily i.v. busulfan in an adult population, with the specific aims of (1) evaluating covariates associated with busulfan clearance, and (2) assessing the feasibility of TDM for outpatient administration of daily TBu with pharmacokinetic sampling over 6 hours. A retrospective pharmacokinetic analysis was conducted in 87 adults receiving daily TBu as part of cyclophosphamide followed by TBU (CY/TBU), fludarabine monophosphate (fludarabine) followed by TBU, or TBU concurrent with fludarabine conditioning. The desired Css was achieved in 85% of patients receiving daily i.v. busulfan. Busulfan clearance was not associated with sex or age, but was associated with the day of dosing and conditioning regimen (P = .0016). In patients receiving...

Idiotype Immunization Following High-Dose Therapy and Autologous Stem Cell Transplantation for Non-Hodgkin Lymphoma

Biology of Blood and Marrow Transplantation — Wed, 06 Jul 2011 04:00:00 +0100

The treatment of low- and intermediate-grade subtypes of malignant lymphoma continues to evolve. Mantle cell lymphoma (MCL) accounts for 6% of all non-Hodgkin lymphoma (NHL) and is generally considered incurable. Although high response rates can be achieved with initial chemotherapy, median survival is only 3-4 years. Intensified consolidation with high-dose therapy (HDT) and autologous stem cell transplantation (ASCT) has been reported to improve progression-free survival (PFS), but most patients eventually relapse. Indolent lymphoma accounts for 35% of all NHL and is associated with a median survival of 9 years. Similar to MCL, it is also generally considered incurable, and the PFS also appears to be improved following HDT/ASCT. We initiated a pilot study to evaluate idiotype (Id) vacci...

EBMT Risk Score Predicts Outcome of Allogeneic Hematopoietic Stem Cell Transplantation in Patients Who Have Failed a Previous Transplantation Procedure

Biology of Blood and Marrow Transplantation — Fri, 01 Jul 2011 04:00:00 +0100

Increasing numbers of allogeneic hematopoietic stem cell transplantation (allo-SCT) are being performed for patients who have failed a previous allogeneic or autologous SCT. We investigated whether the EBMT risk score could predict outcome after a subsequent allo-SCT. We analyzed prognostic factors in 124 consecutive patients who underwent a second transplantation using an allogeneic donor at our institution. Patients with either a first autologous (N = 64) or first allogeneic (N = 60) SCT were included. Age, disease stage, time interval from diagnosis to transplantation, donor type, and donor–recipient sex combination were used to establish a score from 0 to 7 points, from which 3 groups were identified. The 5-year survival probability decreased from 51.7% for risk scores 0-3 (low, n = ...

NCI, NHLBI First International Consensus Conference on Late Effects after Pediatric Hematopoietic Cell Transplantation: State of the Science, Future Directions

Biology of Blood and Marrow Transplantation — Fri, 01 Jul 2011 04:00:00 +0100

On April 28-29, 2011, a conference titled, “Late Effects after Pediatric Hematopoietic Cell Transplantation: State of the Science, Future Directions” was held in Arlington, VA, with a goal of bringing together leaders in the field of pediatric transplantation survivorship to review the current state of knowledge and define gaps in the field, develop consensus on critical areas for future research, and determine the best study designs to effectively address these questions. Over the course of the next several months, 6 summary articles covering the major topics discussed at the conference will be published in this journal, which will define and set forth recommendations for a research agenda to move this field forward over the next decade. (Source: Biology of Blood and Marrow Transplant...

Effect of Early Posttransplantation Tacrolimus Concentration on the Development of Acute Graft-versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation from Unrelated Donors

Biology of Blood and Marrow Transplantation — Mon, 27 Jun 2011 04:00:00 +0100

Only limited data are available regarding the relationship between blood concentration of tacrolimus and its efficacy in preventing acute graft-versus-host disease (aGVHD). We retrospectively evaluated the effects of the whole blood concentration of tacrolimus, which was measured by an automated microparticle enzyme immunoassay, early after allogeneic hematopoietic stem cell transplantation (HSCT) upon the development of aGVHD. Sixty patients, who underwent allogeneic HSCT from serologically human-leukocyte antigen-matched unrelated donors and received continuous infusion of tacrolimus with short-term methotrexate for GVHD prophylaxis, were included in this study. The target range of the blood concentration of tacrolimus was set at 10 to 20 ng/mL, and the level was maintained within this r...

The Hematopoietic Cell Transplantation-Specific Comorbidity Index Fails to Predict Outcomes in High-Risk AML Patients Undergoing Allogeneic Transplantation—Investigation of Potential Limitations of the Index

Biology of Blood and Marrow Transplantation — Mon, 27 Jun 2011 04:00:00 +0100

In the context of allogeneic hematopoietic cell transplantation (allo-HSCT), comorbidities are an important risk factor. Use of the hematopoietic cell transplantation-specific comorbidity index (HSCT-CI), which was developed and validated in Seattle, Washington, has been proposed to predict the probability of nonrelapse mortality (NRM) and overall survival (OS) following allo-HSCT. We performed a single-center retrospective study to validate the prognostic impact of HSCT-CI on transplant outcomes in a cohort of high-risk acute myeloid leukemia patients undergoing allo-HSCT between January 2000 and December 2008. The median patient age at the time of transplantation was 53 years (range: 11-76 years). The median pretransplantation HSCT-CI score was 4 (range: 0-10). Among 340 patients, OS at ...

The Incidence of Veno-Occlusive Disease Following Allogeneic Hematopoietic Stem Cell Transplantation Has Diminished and the Outcome Improved over the Last Decade

Biology of Blood and Marrow Transplantation — Mon, 27 Jun 2011 04:00:00 +0100

The evolution of the incidence, morbidity, and mortality of veno-occlusive disease (VOD) was analyzed in 845 allogeneic hematopoietic stem cell transplantations (allo-HSCTs) performed over 24 years. A total of 117 patients and 73 patients developed VOD following the Seattle and the Baltimore diagnostic criteria, respectively (cumulative incidence 13.8% and 8.8%). The cumulative incidence was significantly higher in the period 1985 to 1996 than in 1997 to 2008 (11.5% vs 6.5%; P = .01). This decline was because of the low incidence of VOD among reduced-intensity conditioning-HSCT (RIC-HSCT) (2.1%) and the reduction among those receiving myeloablative-HSCT from unrelated donors (32.7% vs 10.5%, P = .001). A total of 35 patients had severe VOD (26 with multiorgan failure [MOF]), and 20 died b...

Comparison of Reduced-Intensity Hematopoietic Cell Transplantation with Chemotherapy in Patients Age 60-70 Years with Acute Myelogenous Leukemia in First Remission

Biology of Blood and Marrow Transplantation — Wed, 22 Jun 2011 04:00:00 +0100

We compared the outcomes of patients age 60-70 years with acute myelogenous leukemia receiving reduced-intensity allogeneic hematopoietic cell transplantation (HCT) in first remission (CR1) reported to the Center for International Blood and Marrow Research (n = 94) with the outcomes in patients treated with induction and postremission chemotherapy on Cancer and Leukemia Group B protocols (n = 96). All patients included had been in CR1 for at least 4 months. The HCT recipients were slightly younger than the chemotherapy patients (median age, 63 years vs 65 years; P < .001), but there were no significant between-group differences in the proportion with therapy-related leukemia or in different cytogenetic risk groups. Time from diagnosis to CR1 was longer for the HCT recipients (median, 44 da...

Outcomes of Patients Treated and One Human Leukocyte Antigen–Mismatched Related Compared with Matched Unrelated Donors

Biology of Blood and Marrow Transplantation — Tue, 21 Jun 2011 23:00:00 +0100

In a recently published article, Valcarcel et al. compared outcomes of patients with acute myelogenous leukemia and acute lymphoblastc leukemia in first or second complete remission treated with a one antigen–mismatched related donor (MMRD) by low-resolution HLA typing at 3 loci (HLA-A, -B, and -DRB1) with matched unrelated donor (MUD) transplants typed by high-resolution HLA typing at 4 loci (HLA-A, -B, -C, and -DRB1). As noted in other previous reports, the outcomes were similar in MMRD and MUD transplants by low-resolution HLA typing at 3 loci (HLA-A, -B, and -DRB1) . (Source: Biology of Blood and Marrow Transplantation)

The Role of Anti-HLA Antibodies in Hematopoietic Stem Cell Transplantation

Biology of Blood and Marrow Transplantation — Mon, 20 Jun 2011 04:00:00 +0100

Donor-specific antihuman leukocyte antigen antibodies (DSHA) have been clearly implicated in graft rejection in solid organ transplantation. Their role in allogeneic hematopoietic stem-cell transplantation (allo-HSCT) remains unclear. We summarize here evidence supporting a role for DSHA in graft failure in animal models of allo-HSCT and in clinical settings whenever no full HLA matching occurs. (Source: Biology of Blood and Marrow Transplantation)

Limiting the Daily Total Nucleated Cell Dose of Cryopreserved Peripheral Blood Stem Cell Products for Autologous Transplantation Improves Infusion-Related Safety with No Adverse Impact on Hematopoietic Engraftment

Biology of Blood and Marrow Transplantation — Thu, 16 Jun 2011 04:00:00 +0100

Cryopreserved peripheral blood stem cell (PBSC) products can induce a number of infusion-related adverse reactions, including life-threatening cardiac, neurologic, and other end-organ complications. Preliminary analyses suggested limiting the daily total nucleated cell dose infused might decrease the incidence of these adverse effects. A policy change implemented in December 2007, limiting the total nucleated cell (TNC) dose to (Source: Biology of Blood and Marrow Transplantation)

Planning and Response to Radiation Exposures

Biology of Blood and Marrow Transplantation — Wed, 15 Jun 2011 23:00:00 +0100

The March 11 earthquake and tsunami in Japan has caused the worst radiation disaster since Chernobyl. In the ensuing weeks, dozens of workers have been exposed to radiation while struggling to limit the release of radioactivity from damaged reactor containment vessels and compromised spent-fuel storage pools. Fortunately, no serious immediate injuries have been reported. (Source: Biology of Blood and Marrow Transplantation)

Biology of Blood and Marrow Transplantation — Mon, 13 Jun 2011 17:29:58 +0100

(Source: Biology of Blood and Marrow Transplantation)

Officers and Directors of ASBMT

Biology of Blood and Marrow Transplantation — Mon, 13 Jun 2011 17:29:58 +0100

(Source: Biology of Blood and Marrow Transplantation)

Editorial Board

Biology of Blood and Marrow Transplantation — Mon, 13 Jun 2011 17:29:58 +0100

(Source: Biology of Blood and Marrow Transplantation)

Purpose and Scope

Biology of Blood and Marrow Transplantation — Mon, 13 Jun 2011 17:29:58 +0100

(Source: Biology of Blood and Marrow Transplantation)

Conflicting Impact of Alloreactive NK Cells on Transplantation Outcomes after Haploidentical Transplantation: Do the Reconstitution Kinetics of Natural Killer Cells Create These Differences?

Biology of Blood and Marrow Transplantation — Thu, 09 Jun 2011 04:00:00 +0100

Partially HLA-mismatched related, or HLA-haploidentical, donor stem cell transplantation (SCT) is a feasible therapeutic option for advanced hematologic malignancy patients who lack an HLA-matched related or unrelated donor. Natural killer (NK) cells, a major cell type of the innate immune system, express surface receptors that regulate potent effector functions, such as cytolytic activity and the release of cytokines, and play a central role in the inflammatory response and immunoregulation. Conflicting results have been reported regarding the impact of NK cell alloreactivity on the outcome of haploidentical SCT in leukemic patients. This review summarizes the heterogeneous clinical results and explains the underlying mechanisms with respect to the reconstitution kinetics of NK cells and ...

Selectively T Cell-Depleted Allografts from HLA-Matched Sibling Donors Followed by Low-Dose Posttransplantation Immunosuppression to Improve Transplantation Outcome in Patients with Hematologic Malignancies

Biology of Blood and Marrow Transplantation — Wed, 01 Jun 2011 04:00:00 +0100

We evaluated a photodepletion technique to selectively deplete host-reacting T cells from human leukocyte antigen (HLA)-matched sibling stem cell transplantations with the goal of reducing posttransplantation immunosuppression to improve antimalignancy effects postallografting. Donor lymphocytes were stimulated with irradiated expanded recipient T lymphocytes in an ex vivo mixed lymphocyte reaction. Alloactivated T cells preferentially retaining the photosensitizer 4,5-dibromorhodamine 123 (TH9402) were eliminated by exposure to visible light. Twenty-four patients with hematologic malignancies (16 high risk) conditioned with fludarabine, cyclophosphamide, and totalbody irradiation received a CD34-selected stem cell allograft from an HLA-matched sibling along with 5 × 106/kg selectively d...

Immune Reconstitution in Recipients of Photodepleted HLA-Identical Sibling Donor Stem Cell Transplantations: T Cell Subset Frequencies Predict Outcome

Biology of Blood and Marrow Transplantation — Mon, 30 May 2011 04:00:00 +0100

We evaluated an ex vivo photodepletion (PD) technique to selectively deplete graft-versus-host disease (GVHD) alloreacting T cells given to 24 human leukocyte antigen (HLA)-identical sibling stem cell transplantation (SCT) recipients. Donor lymphocytes were activated by 72-hour exposure to irradiated in vitro expanded recipient T lymphocytes and pulsed with a TH9402 photosensitizer. Alloactivated T cells preferentially retaining the photosensitizer were eliminated by light exposure. The PD product showed an inverted CD4+/CD8+ ratio with greatest depletion occurring in the CD4+ naive and central memory populations. In contrast, the CD8+ naive and effector cells were relatively conserved, reflecting the differential extrusion of TH9402 by T cell subsets. Cytomegalovirus reactive T cells we...

Platelet Recovery Before Allogeneic Stem Cell Transplantation Predicts Posttransplantation Outcomes in Patients with Acute Myelogenous Leukemia and Myelodysplastic Syndrome

Biology of Blood and Marrow Transplantation — Mon, 30 May 2011 04:00:00 +0100

Complete remission (CR) is the gold standard for assessing outcomes following chemotherapy for acute myelogenous leukemia (AML). “CRp,” a response criterion defined as fulfillment of all criteria for CR except platelet count recovery to ≥100 × 109/L, is associated with inferior outcomes following chemotherapy. The prognostic importance of CRp before allogeneic stem cell transplantation (allo-SCT) remains unknown. We analyzed a cohort of AML (n = 334) and myelodysplastic syndrome (MDS; n = 10) patients to determine the prognostic significance of achieving CR versus CRp before allo-SCT. At time of transplantation, 266 patients were in CR (CR1 and ≥CR2) and 78 in CRp (CR1p and ≥CR2p). Median follow-up was 38 months (3-131 months). Overall survival, progression-free survival, and no...

Outcome of Myeloablative Conditioning and Unrelated Donor Hematopoietic Cell Transplantation for Childhood Acute Lymphoblastic Leukemia in Third Remission

Biology of Blood and Marrow Transplantation — Fri, 27 May 2011 04:00:00 +0100

We conducted a retrospective study of 155 children who underwent unrelated donor hematopoietic cell transplantation (HCT) between 1990 and 2005 for acute lymphoblastic leukemia in third remission. The median patient age was 11 years, the median time from diagnosis to first relapse was 36 months, and the median time from first relapse to second relapse was 26 months. Stem cell sources were bone marrow (n = 115), peripheral blood (n = 11), and cord blood (n = 29). All patients received a myeloablative pretransplantation conditioning regimen. The 5-year estimates of leukemia-free survival, relapse, and nonrelapse mortality were 30%, 25%, and 45%, respectively. In multivariate analysis, the only risk factor associated with relapse was the interval between the first relapse and the second rela...

Cord Blood Transplantation from Unrelated Donors for Children with Acute Lymphoblastic Leukemia in Japan: The Impact of Methotrexate on Clinical Outcomes

Biology of Blood and Marrow Transplantation — Wed, 25 May 2011 04:00:00 +0100

Cord blood transplantation (CBT) from an unrelated donor is recognized as one of the major treatment modalities in allogeneic stem cell transplantation (SCT) for children with hematologic malignancies. We analyzed the clinical outcomes of CBT for children with acute lymphoblastic leukemia (ALL) in Japan and identified the risk factors for the transplant outcomes. From 1997 to 2006, 332 children with ALL underwent CBT from unrelated donors, 270 of which had no prior transplant. Their disease statuses at transplant were first complete remission (CR) (n = 120), second CR (n = 71), and more advanced stages (n = 75). As preconditioning for SCT, total body irradiation (TBI) was given to 194 patients and, for the prophylaxis of graft-versus-host disease (GVHD), methotrexate (MTX) was given to 159...

Early and Late Extensive Chronic Graft-versus-Host Disease in Children Is Characterized by Different Th1/Th2 Cytokine Profiles: Findings of the Children's Oncology Group Study ASCT0031

Biology of Blood and Marrow Transplantation — Wed, 25 May 2011 04:00:00 +0100

Numerous mechanisms underlie chronic graft-versus-host disease (cGVHD), including skewing of Th1/Th2 cytokine expression. There are biological differences between early-onset and late-onset cGVHD. To test whether different Th1/Th2 cytokines are associated with early- or late-onset cGVHD, peripheral blood was collected from 63 children enrolled on the Children's Oncology Group Phase III trial ASCT0031 evaluating hydroxychloroquine therapy for newly diagnosed extensive cGVHD. mRNA expression of interferon (IFN)-γ and interleukin (IL)-2, -4, and -10 from stimulated peripheral blood mononuclear cells was evaluated by quantitative polymerase chain reaction. Early-onset cGVHD (n = 33) was characterized by decreased expression of IFN-γ and IL-2 mRNA after nonspecific phorbol 12-myristate 13-ace...

Adoptive Immunotherapy with Cytokine-Induced Killer Cells for Patients with Relapsed Hematologic Malignancies after Allogeneic Hematopoietic Cell Transplantation

Biology of Blood and Marrow Transplantation — Wed, 25 May 2011 04:00:00 +0100

Donor leukocyte infusions induce remissions in some patients with hematologic malignancies who relapse after allogeneic hematopoietic cell transplantation (HCT); however, graft-versus-host disease (GVHD) remains the major complication of this strategy. Cytokine-induced killer (CIK) cells are a unique population of cytotoxic T lymphocytes that express the CD3+CD56+ phenotype and show marked up-regulation of the natural killer cell receptor NKG2D (CD314). CIK cells are non–major histocompatibility complex–restricted and NKG2D-dependent in target recognition and cytotoxicity. We explored the feasibility of ex vivo expansion of allogeneic CIK cells in patients with relapsed hematologic malignancies after allogeneic HCT. Eighteen patients (median age, 53 years; range, 20-69 years) received...

Genomic Aberrations and Survival of Patients with Light-Chain-Only Multiple Myeloma Undergoing Autologous Stem Cell Transplantation

Biology of Blood and Marrow Transplantation — Mon, 23 May 2011 04:00:00 +0100

The majority of patients with multiple myeloma (MM) have intact immunoglobulin, but in a subset of patients (∼15%), their tumors produce monoclonal light chains only (LCO). Although specific genomic aberrations have emerged as a major prognostic factor in MM, their incidence and prognostic impact on LCO myeloma patients are not clear. We therefore investigated a cohort of 86 LCO MM cases diagnosed and treated with autologous stem cell transplantation at our institution. Overall, genomic risk factors del(13q), del(17p), t(4;14), 1p loss, and 1q21 gain were detected by cytoplasmic fluorescence in situ hybridization (cIg-FISH) in 40.6%, 18.5%, 11.9%, 18.8%, and 25% of the cases, respectively. Patients with del(13q) and 1q gains had a significantly shorter overall survival (OS) (median 80.4 ...

Malignancies after Hematopoietic Cell Transplantation for Primary Immune Deficiencies: A Report from the Center for International Blood and Marrow Transplant Research

Biology of Blood and Marrow Transplantation — Mon, 23 May 2011 04:00:00 +0100

We describe the incidence of malignancy in patients with primary immunodeficiency disorders (PIDD) following hematopoietic cell transplantation (HCT). From the Center for International Blood and Marrow Transplant Research, 2266 PIDD patients who had undergone allogeneic HCT between 1968 and 2003 were identified. Patient, disease, and transplant factors for development of malignancy were examined and pathology reports for reported malignancies reviewed independently by a pathologist for confirmation. The incidence of malignancy was highest for Wiskott-Aldrich syndrome (3.3%), with an overall incidence of 2.3% for PIDD. Post-HCT malignancy was confirmed for 52 of 63 reported cases. Forty-five of 52 patients developed posttransplant lymphoproliferative disorders (PTLD) at a median of 3 months...

Safety and Immunogenicity of the Live Attenuated Varicella Vaccine Following T Replete or T Cell-Depleted Related and Unrelated Allogeneic Hematopoietic Cell Transplantation (alloHCT)

Biology of Blood and Marrow Transplantation — Mon, 23 May 2011 04:00:00 +0100

There are limited studies assessing the live attenuated varicella vaccine following allogeneic hematopoietic cell transplantation (alloHCT). Because of the morbidity of varicella acquired after childhood, we immunized and retrospectively analyzed the safety and immunogenicity of this vaccine in 46 varicella zoster virus (VZV) seronegative patients (Source: Biology of Blood and Marrow Transplantation)

Biology of Blood and Marrow Transplantation — Fri, 20 May 2011 16:56:41 +0100

(Source: Biology of Blood and Marrow Transplantation)

Officers and Directors of ASBMT

Biology of Blood and Marrow Transplantation — Fri, 20 May 2011 16:56:41 +0100

(Source: Biology of Blood and Marrow Transplantation)

Editorial Board

Biology of Blood and Marrow Transplantation — Fri, 20 May 2011 16:56:41 +0100

(Source: Biology of Blood and Marrow Transplantation)

Masthead (Purpose and Scope)

Biology of Blood and Marrow Transplantation — Fri, 20 May 2011 16:56:41 +0100

(Source: Biology of Blood and Marrow Transplantation)

Rationale and Design of the Chronic GVHD Cohort Study: Improving Outcomes Assessment in Chronic GVHD

Biology of Blood and Marrow Transplantation — Thu, 19 May 2011 23:00:00 +0100

This study will evaluate the performance of proposed prognostic factors, measures of disease activity, and surrogate endpoints for therapeutic response. Data are collected at 6-month intervals in a heterogeneous population of patients reflecting modern transplant techniques and posttransplantation clinical management (target enrollment 672 with cGVHD from 10 transplantation centers). This report describes the rationale, design, and methods of the cGVHD cohort study, and invites other investigators to collaborate with the Consortium to analyze data or specimens. (Source: Biology of Blood and Marrow Transplantation)

Allogeneic Hematopoietic Cell Transplantation for Chronic Myelofibrosis in Australia and New Zealand: Older Recipients Receiving Myeloablative Conditioning at Increased Mortality Risk

Biology of Blood and Marrow Transplantation — Thu, 12 May 2011 04:00:00 +0100

This study shows a clear increase in annual numbers of allogeneic HCT performed for CM in Australia and New Zealand in recent years. Five-year survival was favorable compared with international studies, but for older recipients who received myeloablative conditioning, mortality risk was elevated. (Source: Biology of Blood and Marrow Transplantation)

Progressive Improvement in Cutaneous and Extracutaneous Chronic Graft-versus-Host Disease after a 24-Week Course of Extracorporeal Photopheresis—Results of a Crossover Randomized Study

Biology of Blood and Marrow Transplantation — Thu, 12 May 2011 04:00:00 +0100

In conclusion, progressive improvement in cutaneous and extracutaneous cGVHD was observed after a 24-week course of ECP in patients who previously had no clinical improvement or exhibited worsening of cGVHD while receiving standard immunosuppressive therapy alone in a randomized study. These results confirm previous findings and support the notion that prolonged ECP appears to be necessary for optimal therapeutic effects in corticosteroid-refractory cGVHD patients. (Source: Biology of Blood and Marrow Transplantation)

Effect of Obesity on Outcomes after Autologous Hematopoietic Stem Cell Transplantation for Multiple Myeloma

Biology of Blood and Marrow Transplantation — Thu, 12 May 2011 04:00:00 +0100

Obesity has implications for chemotherapy dosing and selection of patients for therapy. Autologous hematopoietic stem cell transplant (AutoHCT) improves outcomes for patients with multiple myeloma, but optimal chemotherapy dosing for obese patients is poorly defined. We analyzed the outcomes of 1087 recipients of AutoHCT for myeloma reported to the CIBMTR between 1995 and 2003 who received high-dose melphalan conditioning, with or without total body irradiation (TBI). We categorized patients by body mass index (BMI) as normal, overweight, obese, or severely obese. There was no overall effect of BMI on progression-free survival (PFS), overall survival (OS), progression, or nonrelapse mortality (NRM). In patients receiving melphalan and TBI conditioning, obese and severely obese patients had...

Improved Survival after Allogeneic Hematopoietic Stem Cell Transplantation in Recent Years. A Single-Center Study

Biology of Blood and Marrow Transplantation — Thu, 12 May 2011 04:00:00 +0100

This study shows that the combined efforts to improve outcome after HSCT have been very effective. Even though we now treat older patients with more advanced disease and use more alternative HLA nonidentical donors, OS and TRM have improved. The problem of relapse still has to be remedied. Thus, several different developments together have resulted in significantly lower TRM and improved survival after HSCT over the last few years. (Source: Biology of Blood and Marrow Transplantation)

Treatment Options for Transformed Lymphoma: Incorporating Allogeneic Stem Cell Transplantation in a Multimodality Approach

Biology of Blood and Marrow Transplantation — Wed, 11 May 2011 23:00:00 +0100

Transformed non-Hodgkin lymphoma (TL) arising from follicular lymphoma carries a poor prognosis, and the median survival time after transformation is approximately 10 to 12 months. Standard chemotherapy and radioimmunotherapy have offered promising responses; however, the duration of response does not appear to last long. Several studies evaluating the role of autologous stem cell transplantation (auto-SCT) as a salvage regimen have been reported, and a subset of patients benefit from this modality of treatment. With an improvement in supportive care, outcome after allogeneic stem cell transplantation (allo-SCT) has been improved significantly over past decades; however, very limited data are available for TL. In the era of emerging novel therapies, the actual timing, optimal conditioning ...

Anti-HLA Antibodies in Double Umbilical Cord Blood Transplantation

Biology of Blood and Marrow Transplantation — Wed, 04 May 2011 04:00:00 +0100

Recent registry data suggest that host-versus-graft alloreactions mediated by anti-donor HLA antibodies in recipients of adult allogeneic hematopoietic stem cells or single-unit umbilical cord blood (UCB) contribute to the risk of graft failure. The present study evaluated the impact of anti-HLA antibodies on engraftment and unit predominance in 126 double-UCB (dUCB) recipients. Eighteen dUCB recipients were identified with at least 1 of 2 UCB units recognized by anti-HLA antibodies directed against donor-directed HLA-specific antibodies (DSAs). Overall, 9 of 12 patients who had DSAs against 1 of the 2 UCB units composing the graft and 5 of 6 patients who had DSAs against both units engrafted. The cumulative incidence of engraftment was similar in patients with and without DSAs (83% vs 78%...

Fludarabine, Antithymocyte Globulin, and Very Low-Dose Busulfan for Reduced-Intensity Conditioning before Allogeneic Stem Cell Transplantation in Patients with Lymphoid Malignancies

Biology of Blood and Marrow Transplantation — Wed, 04 May 2011 04:00:00 +0100

This retrospective report compared the results of a reduced-intensity conditioning (RIC) regimen including fludarabine (Flu), and very low-dose oral busulfan (BU) (4 mg/kg total dose) in combination with antithymocyte globulin (ATG) (Flu/ATG/BU) to the classical Flu and low-dose total body irradiation (TBI) (2 Gy) regimen (Flu/TBI) in patients with lymphoid malignancies. With a median follow-up of 42 months, the cumulative incidence of transplant-related mortality (TRM) was 22% in the Flu/ATG/BU group versus 41% in the Flu/TBI group (P = .09). Grade 3-4 acute graft-versus-host disease (aGVHD) and extensive chronic GVHD (cGVHD) incidents were 15% versus 44% (P = .006), and 12% versus 58% (P = .0003), in the Flu/ATG/BU group versus the Flu/TBI group, respectively. The Kaplan-Meier estimate o...

Incidence and Prognostic Value of Eosinophilia in Chronic Graft-versus-Host Disease after Nonmyeloablative Hematopoietic Cell Transplantation

Biology of Blood and Marrow Transplantation — Wed, 04 May 2011 04:00:00 +0100

Data from a number of cohorts indicate that eosinophilia (Eo) could be associated with better outcomes following allogeneic hematopoietic cell transplant (HCT). However, little is known about its significance and prognostic value in chronic graft-versus-host disease (cGVHD) after nonmyeloablative (NMA) transplantation. Data were collected from 170 patients who underwent HCT using the same preparative regimen and GVHD prophylaxis. Donors were 6/6 HLA-matched siblings and stem cell source was peripheral blood. An eosinophil count of ≥0.5 × 109/L was defined as Eo. Patients were transplanted mainly for lymphoproliferative disorders. Median age and follow-up were 54 years and 58 months, respectively. Incidents of grade II-IV acute GVHD (aGVHD) and cGVHD were 8.2% and 81.2%. Median time from...

Prognostic Significance of FDG-PET in Relapsed or Refractory Classical Hodgkin Lymphoma Treated with Standard Salvage Chemotherapy and Autologous Stem Cell Transplantation

Biology of Blood and Marrow Transplantation — Wed, 04 May 2011 04:00:00 +0100

Positron emission tomography using [18F]fluorodeoxyglucose (FDG-PET) has emerged as the standard response assessment tool in frontline therapy for classical Hodgkin lymphoma (cHL). The ability of FDG-PET to predict outcomes in patients with relapsed cHL treated with modern standard salvage chemotherapy and autologous stem cell transplantation (ASCT) remains uncertain. Forty-six patients with relapsed/refractory cHL treated from 2001 to 2007 with standard salvage/ASCT therapy had FDG-PET available for blinded review. The results of pre-ASCT FDG-PET interpreted by the international harmonization project (IHP) criteria were compared with published prognostic models for prediction of event-free survival (EFS) and overall survival (OS). Overall, 3-year EFS was 62% and OS was 78%, with a median ...

Expression of Activating KIR2DS2 and KIR2DS4 Genes after Hematopoietic Cell Transplantation: Relevance to Cytomegalovirus Infection

Biology of Blood and Marrow Transplantation — Mon, 02 May 2011 04:00:00 +0100

In this report, expression of the KIR2DS2 and KIR2DS4 genes, as measured by mRNA-based quantitative polymerase chain reaction in both the donor cells and the HCT recipient cells, was studied relative to CMV reactivation. In the control samples from healthy donors, the median range for KIR2DS2 and KIR2DS4 expression was low, with 35% of donors considered null-expressers. Interestingly, KIR2DS2 and KIR2DS4 expression was elevated after HCT compared with donor expression before HCT, and was significantly elevated in CMV viremic compared with CMV nonviremic HCT recipients. The CMV seropositivity of donors was not associated with activating KIR expression, and donor null expression in those with the KIR2DS2 or KIR2DS4 genotype was not predictive for CMV reactivation in the recipient. After cont...

Pretransplantation Liver Function Impacts on the Outcome of Allogeneic Hematopoietic Stem Cell Transplantation: A Study of 455 Patients

Biology of Blood and Marrow Transplantation — Fri, 29 Apr 2011 04:00:00 +0100

In conclusion, hepatic dysfunction before allo-SCT is frequent and has an impact on transplantation outcomes. The best indicator of liver dysfunction still has to be determined. (Source: Biology of Blood and Marrow Transplantation)

Differences in T Cell Depletion and Intestinal Mucositis Explain Inconsistent Effects of NOD2/CARD15 Polymophisms in SCT

Biology of Blood and Marrow Transplantation — Fri, 29 Apr 2011 04:00:00 +0100

The role of innate immunity is increasingly prominent in stem cell transplantation (SCT) and has recently been reviewed by Penack et al. . This has been largely due to the recognition of a role for genetic variations, mainly single nucleotide polymorphisms (SNPs), in innate immune genes impacting the outcome of SCT regarding infections, graft-versus-host disease (GVHD), and treatment-related mortality (TRM) . The landmark study of Holler et al. showed that NOD2 polymorphisms do increase the risk for acute GVHD (aGVHD) and TRM in matched related SCT and was a breakthrough in the field of non-HLA genetics in SCT (A) . However, confusion arose when several others were unable to confirm the strong clinical manifestations of these polymorphisms. This underscored the fact that the influence of...

Factors Influencing the Outcome of a Second Autologous Stem Cell Transplant (ASCT) in Relapsed Multiple Myeloma: A Study from the British Society of Blood and Marrow Transplantation Registry

Biology of Blood and Marrow Transplantation — Tue, 26 Apr 2011 04:00:00 +0100

Autologous stem cell transplant as primary (first ASCT) therapy in multiple myeloma (MM) is standard practice. The role of a second ASCT as management of relapsed disease remains uncertain. We conducted a retrospective case-matched control analysis on patients (n = 106) who underwent a second ASCT compared with conventional chemotherapy (CCT) as for relapsed MM. The median age was 53 years (range: 26-75) and median follow-up 48 months (range: 8, 136). The cumulative incidence of 1 and 5 years nonrelapse mortality (NRM) was 7% (95% confidence interval [CI] 3%-13%) and 12% (95% CI 7%-19%), with a second ASCT inducing a greater partial remission (PR) rate of 63%. The 4-year overall survival (OS) rate was 33% (95% CI 24%-45%). Factors associated with improved OS and progression-free survival (...

Changes of Hepatitis B Virus Serologic Status after Allogeneic Hematopoietic Stem Cell Transplantation and Impact of Donor Immunity on Hepatitis B Virus

Biology of Blood and Marrow Transplantation — Tue, 26 Apr 2011 04:00:00 +0100

In this study, the frequency of HBV RS at a single center in Korea, endemic for HBV, was evaluated. Also, the influence of the donor’s immunity for HBV on posttransplantation HBV serologic changes in recipients was also investigated. A total of 288 patients underwent allogeneic transplantation between February 1996 and June 2008. We retrospectively reviewed the medical records of 288 patients and their paired donors. Among the 268 HBsAg(−) patients, 205 were assessed for posttransplantation HBsAg, and 114 (55.6%) of 205 had HBcAb before transplantation. With a median follow-up of 77.9 months, 3 of 114 patients experienced HBV RS (2.6%). With regard to donor immunity, significantly more patients with anti-HBs(−) donors experienced anti-HBs loss (P = .006), and the donor anti-HBs showe...

Human Herpesvirus 6 Infection after Hematopoietic Cell Transplantation: Is Routine Surveillance Necessary?

Biology of Blood and Marrow Transplantation — Wed, 20 Apr 2011 04:00:00 +0100

Human herpesvirus 6 (HHV6) may be an important pathogen following allogeneic hematopoietic cell transplantation (HCT). We prospectively evaluated weekly HHV6 viremia testing after allogeneic HCT using a quantitative polymerase chain reaction (PCR)-based assay. HHV-6 viremia was detected in 46 of 82 (56%) patients at a median of 23 days post-HCT (range: day +10 to +168). More males (65% vs females 39%, P = .03) and recipients of umbilical cord blood (UCB 69% vs unrelated donor [URD], 46% vs sibling donor [20%] grafts, P = 0.01) reactivated HHV-6. Patients with HHV6 viremia had more cytomegalovirus (CMV) reactivation (26% vs 5.5%, P = .01) and unexplained fever and rash (23.9% vs 2.7%, P = .01) compared with patients without HHV6 viremia. High-level HHV6 (≥25,000 copies/mL) versus lower ...

Retraction notice to “Effect of Oral Crotherapy on Mucositis-Related Pain and Patient Functioning in Hematopoeitic Stem Cell Transplant Recipients Receiving High-Dose Melphalan” [Biol Blood Marrow Tr 16/2S (2010) S322]

Biology of Blood and Marrow Transplantation — Tue, 19 Apr 2011 23:00:00 +0100

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This abstract has been retracted at the request of the authors and Editor-in-Chief. The abstract was presented at an earlier meeting and without the full consent of all authors. (Source: Biology of Blood and Marrow Transplantation)

Intravenous Busulfan-Cyclophosphamide as a Preparative Regimen Before Allogeneic Hematopoietic Stem Cell Transplantation for Adult Patients with Acute Lymphoblastic Leukemia

Biology of Blood and Marrow Transplantation — Mon, 18 Apr 2011 04:00:00 +0100

This study demonstrates that i.v. BU/CY can be considered a feasible conditioning regimen for adult ALL, with low incidences of VOD and TRM. (Source: Biology of Blood and Marrow Transplantation)

Biology of Blood and Marrow Transplantation — Thu, 14 Apr 2011 17:53:56 +0100

(Source: Biology of Blood and Marrow Transplantation)

Officers and Directors of ASBMT

Biology of Blood and Marrow Transplantation — Thu, 14 Apr 2011 17:53:56 +0100

(Source: Biology of Blood and Marrow Transplantation)

Editorial Board

Biology of Blood and Marrow Transplantation — Thu, 14 Apr 2011 17:53:56 +0100

(Source: Biology of Blood and Marrow Transplantation)

Masthead (Purpose and Scope)

Biology of Blood and Marrow Transplantation — Thu, 14 Apr 2011 17:53:56 +0100

(Source: Biology of Blood and Marrow Transplantation)

A Multicenter Pilot Evaluation of the National Institutes of Health Chronic Graft-versus-Host Disease (cGVHD) Therapeutic Response Measures: Feasibility, Interrater Reliability, and Minimum Detectable Change

Biology of Blood and Marrow Transplantation — Wed, 13 Apr 2011 04:00:00 +0100

We report the results of 4 consecutive pilot trials evaluating the feasibility and estimating the interrater reliability and minimum detectable change of these response criteria. Hematology-oncology clinicians with limited experience in applying the NIH cGVHD response criteria (n = 34) participated in a 2.5-hour training session on response evaluation in cGVHD. Feasibility and interrater reliability between subspecialty cGVHD experts and this panel of clinician raters were examined in a sample of 25 children and adults with cGVHD. The minimum detectable change was calculated using the standard error of measurement. Clinicians’ impressions of the brief training session, the photo atlas, and the response criteria documentation tools were generally favorable. Performing and documenting the ...

Contribution of HLA-A/B/C/DRB1/DQB1 Common Haplotypes to Donor Search Outcome in Unrelated Hematopoietic Stem Cell Transplantation

Biology of Blood and Marrow Transplantation — Wed, 13 Apr 2011 04:00:00 +0100

In unrelated hematopoietic stem cell transplantation (HSCT), the prediction of donor search outcome at the time of search initiation is of great value for the physicians to delineate the strategy of patient care. The probability of finding an unrelated donor is high for patients who carry at least 1 of the 10 most common HLA haplotypes in Caucasians. As only 10% to 20% patients respond to this criterion, here we aimed at finding additional common haplotypes to improve the prediction of a successful search. HLA broad HLA-A/B/DRB1 haplotypes that were observed with frequencies ≥0.19% in patient families of European origin and that split into ≤2 predominant 4-digit HLA-A/B/C/DRB1/DQB1 haplotypes were considered as common. Carriage of at least 1 of those in 168 patients of various geograph...

Histology and Time to Progression Predict Survival for Lymphoma Recurring after Reduced-Intensity Conditioning and Allogeneic Hematopoietic Cell Transplantation

Biology of Blood and Marrow Transplantation — Wed, 13 Apr 2011 04:00:00 +0100

Reduced-intensity conditioning (RIC) before allogeneic hematopoietic cell transplantation (HCT) is increasingly used as a potentially curative option for patients with advanced lymphoma; however, relapse remains a major challenge. Unfortunately, little data are available on outcomes, predictors of survival, and results of specific management strategies in these patients. In the present study, a total of 101 consecutive relapses occurred and were evaluated in 280 patients with lymphoma who underwent RIC HCT. Diseases included aggressive non-Hodgkin lymphoma (NHL) (n = 42), indolent NHL (n = 33), and Hodgkin lymphoma (HL) (n = 26). Median time to relapse was 90 days (range, 3-1275 days), and graft-versus-host disease at relapse was present in 56 patients (55%). Interventions after relapse in...

Immunosuppressive Effects of Multiple Myeloma Are Overcome by PD-L1 Blockade

Biology of Blood and Marrow Transplantation — Tue, 12 Apr 2011 23:00:00 +0100

Multiple myeloma is an incurable plasma cell malignancy. Patients who fail conventional therapy are frequently treated with hematopoietic stem cell transplantation (HSCT), which results in reduced tumor burden, but the patients subsequently relapse from sites of chemotherapy-resistant disease. Using the 5T33 murine model of myeloma and a previously successful immunotherapy regimen consisting of autologous (syngeneic) HSCT and cell-based vaccine administration, we were unable to improve survival of myeloma-bearing mice. The 5T33 tumor line, similar to malignant plasma cells from myeloma patients, expresses high levels of programmed death receptor ligand-1 (PD-L1), which binds to the inhibitory receptor, PD-1. We observed that T cells from myeloma-bearing mice express high levels of PD-1, wh...

Allogeneic Transplant Physician and Center Capacity in the United States

Biology of Blood and Marrow Transplantation — Tue, 12 Apr 2011 23:00:00 +0100

Shortage of manpower and center capacity is expected to be a major challenge to the anticipated future growth in the utilization of allogeneic hematopoietic cell transplantation (HCT) in the United States. Using data from the National Marrow Donor Program’s Transplant Center Network Renewal Survey, we describe transplant center and transplant physician capacity in the United States from 2005 to 2009. Over this 5-year period, the number of allogeneic transplants increased by 30%, bed capacity increased by 17%, and physician full-time equivalents increased by 26%. The number of related donor HCT increased by 15% and unrelated donor HCT increased by 45%. In addition to large centers, small- and medium-sized centers also made a major contribution to overall national transplant volumes for bo...

Cigarette Smoking and Outcomes after Allogeneic Hematopoietic Stem Cell Transplantation

Biology of Blood and Marrow Transplantation — Tue, 29 Mar 2011 23:00:00 +0100

Abnormal lung function is a known risk factor for poor outcomes in the allogeneic hematopoietic stem cell transplantation (HSCT) population, although the specific causes of these abnormalities have not been well explored. There is limited data on the effect of cigarette smoking on transplantation outcomes. We conducted a retrospective observational cohort study of 845 consecutive patients age ≥18 years who underwent allogeneic HSCT at the Seattle Cancer Care Alliance/Fred Hutchinson Cancer Research Center. Smoking exposure was defined by quit time, smoking status (never, former, and current), and log2-transformed pack-years. The main outcomes were time to respiratory failure within 100 days of transplantation, relapse, and nonrelapse mortality. In multivariable analyses, a 2-fold increas...

Trends of Hematopoietic Stem Cell Transplantation in the Eastern Mediterranean Region, 1984-2007

Biology of Blood and Marrow Transplantation — Sun, 27 Mar 2011 23:00:00 +0100

Hematopoietic stem cell transplantation (HSCT) activity was surveyed in the 9 countries in the World Health Organization Eastern Mediterranean region that reported transplantation activity. Between the years of 1984 and 2007, 7933 transplantations were performed. The number of HSCTs per year has continued to increase, with a plateau in allogeneic HSCT (allo-HSCT) between 2005 and 2007. Overall, a greater proportion of transplantations were allo-HSCT (n = 5761, 77%) compared with autologous HSCT (ASCT) (n = 2172, 23%). Of 5761 allo-HSCT, acute leukemia constituted the main indication (n = 2124, 37%). There was a significant proportion of allo-HSCT for bone marrow failures (n = 1001, 17%) and hemoglobinopathies (n = 885, 15%). The rate of unrelated donor transplantations remained low, with o...

Relapsing Hematologic Malignancies after Haploidentical Hematopoietic Stem Cell Transplantation

Biology of Blood and Marrow Transplantation — Sun, 27 Mar 2011 23:00:00 +0100

Haploidentical hematopoietic stem cell transplantation (HSCT) is a potentially curative therapeutic regimen that could increase donor availability to nearly 100%. Rapid advances in medical technology and the application of novel drugs mean that most haploidentical HSCT-associated complications can now be prevented or remarkably well controlled, even cured. However, relapsing hematologic malignancy remains a major cause of death in haploidentical HSCT recipients. Haploidentical HSCT should theoretically trigger a more potent graft-versus-tumor effect compared with human leukocyte antigen-identical transplantation, due mainly to the major histocompatibility complex and minor histocompatibility anitigen disparities on donors’ immune cells and recipients’ tumor cells. The underlying mechan...

Roles of CD28, CTLA4, and Inducible Costimulator in Acute Graft-versus-Host Disease in Mice

Biology of Blood and Marrow Transplantation — Sun, 27 Mar 2011 23:00:00 +0100

In this study, we evaluated the roles of CD28, CTLA4, and ICOS in the pathogenesis of acute GVHD after myeloablative allogeneic bone marrow transplantation. Unexpectedly, we found that blocking CD28 and CTLA4 signals using the clinically relevant reagent CTLA4-Ig increases the severity of GVHD mediated by CD4+ T cells, and that such treatment does not add any benefit to the blockade of ICOS. In contrast, selectively blocking CD28 and ICOS, but not CTLA4, prevents GVHD more effectively than blocking either CD28 or ICOS alone. Taken together, these results indicate that CD28 and ICOS are synergistic in promoting GVHD, whereas the CTLA4 signal is required for T cell tolerance regardless of ICOS signaling. Thus, blocking CD28 and ICOS while sparing CTLA4 represents a promising approach for abr...

Variation in Management of Immune Suppression after Allogeneic Hematopoietic Cell Transplantation

Biology of Blood and Marrow Transplantation — Fri, 25 Mar 2011 04:00:00 +0100

Practice variation in transplant physician management of immune suppression (IS) after allogeneic hematopoietic cell transplantation (HCT) is anticipated to have important consequences, but has not been characterized to date. We conducted a national survey of transplant physician members of the American Society for Blood and Marrow Transplantation to discern variation in IS management, characterize the burden of graft-versus-host disease (GVHD) emerging in the setting of IS taper, and describe the proportion of HCT recipients who successfully discontinue IS by 2 and 5 years post-HCT. There was marked heterogeneity in IS discontinuation practice, with variation in initiation of taper, sequence of agents tapered, frequency of changes, and strategy utilized. Twenty-five percent reported no co...

Activation and Expansion of CD8+ T Effector Cells in Patients with Chronic Graft-versus-Host Disease

Biology of Blood and Marrow Transplantation — Fri, 25 Mar 2011 00:00:00 +0100

We tested the hypothesis that changes in the phenotype of CD8+ T cells from patients with chronic graft-versus-host disease (cGVHD) correlate with disease activity, and resolve or normalize in clinically tolerant patients successfully withdrawn from immunosuppression therapy (IST). No significant difference was found in the absolute CD8+ T cell counts among cGVHD patients, tolerant patients, and healthy controls. However, compared with healthy normal controls, CD8+ T cells from cGVHD patients had decreased expression of the IL-7 receptor and an increase in effector T cells, Ki-67, and perforin expression and apoptosis, suggesting that activation, differentiation, and proliferation of host-reactive CD8+ effector T cells is a mechanism by which cGVHD is sustained and persists. The increase i...

Spontaneous Autologous Graft-versus-Host Disease in Plasma Cell Myeloma Autograft Recipients: Flow Cytometric Analysis of Hematopoietic Progenitor Cell Grafts

Biology of Blood and Marrow Transplantation — Fri, 25 Mar 2011 00:00:00 +0100

Nine plasma cell myeloma patients spontaneously developed histologically proven autologous graft-versus-host disease (GVHD) limited predominantly to the gastrointestinal tract within 1 month of initial autologous hematopoietic cell transplantation (AHCT) using high-dose melphalan conditioning. All recipients responded promptly to systemic and nonabsorbable oral corticosteroid therapy. All patients previously received systemic therapy with thalidomide, lenalidomide, or bortezomib before AHCT. Using enzymatic amplification staining-enhanced flow cytometry, we evaluated expression of selected transcription regulators, pathway molecules, and surface receptors on samples of the infused hematopoietic cell grafts. We demonstrated significantly enhanced expression of GATA-2, CD130, and CXCR4 on CD...

A Retrospective Comparison of Tacrolimus versus Cyclosporine with Methotrexate for Immunosuppression after Allogeneic Hematopoietic Cell Transplantation with Mobilized Blood Cells

Biology of Blood and Marrow Transplantation — Mon, 21 Mar 2011 00:00:00 +0100

This retrospective study was performed to compare results with tacrolimus versus cyclosporine in combination with methotrexate for immunosuppression after allogeneic hematopoietic cell transplantation (HCT) with granulocyte colony-stimulating factor–mobilized blood cells. The cohort included 456 consecutive patients who received first allogeneic T cell-replete HCT with mobilized blood cells from related or unrelated donors after high-intensity conditioning for treatment of hematologic malignancies. Study endpoints included grades II-IV acute graft-versus-host disease (aGVHD), grades III-IV aGVHD, chronic GVHD (cGVHD), end of treatment for cGVHD, overall mortality, disease-free survival (DFS), recurrent malignancy, and nonrelapse mortality (NRM). Adjusted multivariate Cox regression analy...

Erratum

Biology of Blood and Marrow Transplantation — Mon, 21 Mar 2011 00:00:00 +0100

In “Translational Research Efforts in Biomarkers and Biology of Early Transplant-Related Complications” (Cooke et al., Biol Blood Marrow Transplant 2010;17:S101-S108), the author Enrique Carerras should be listed as Enric Carreras. (Source: Biology of Blood and Marrow Transplantation)

Biology of Blood and Marrow Transplantation — Thu, 17 Mar 2011 17:31:12 +0100

(Source: Biology of Blood and Marrow Transplantation)

Officers and Directors of ASBMT

Biology of Blood and Marrow Transplantation — Thu, 17 Mar 2011 17:31:12 +0100

(Source: Biology of Blood and Marrow Transplantation)

Editorial Board

Biology of Blood and Marrow Transplantation — Thu, 17 Mar 2011 17:31:12 +0100

(Source: Biology of Blood and Marrow Transplantation)

Masthead (Purpose and Scope)

Biology of Blood and Marrow Transplantation — Thu, 17 Mar 2011 17:31:12 +0100

(Source: Biology of Blood and Marrow Transplantation)

News-April 2011

Biology of Blood and Marrow Transplantation — Thu, 17 Mar 2011 17:31:12 +0100

Daniel J. Weisdorf, MD, has been installed as president of the American Society for Blood and Marrow Transplantation. He is professor of medicine at the University of Minnesota in Minneapolis, the director of the University of Minnesota’s Adult Blood and Marrow Transplant Program, and is scientific director for the National Marrow Donor Program and senior research advisor for the CIBMTR. (Source: Biology of Blood and Marrow Transplantation)

Reversible Ureteral Obstruction due to Polyomavirus Infection after Percutaneous Nephrostomy Catheter Placement

Biology of Blood and Marrow Transplantation — Thu, 10 Mar 2011 05:00:00 +0100

We report a series of 6 HSCT recipients who developed obstructive uropathy of the upper urinary tract system secondary to inflammation and hemorrhage involving the upper uroepithelium, causing ureteral stenosis. Temporary placement of a percutaneous nephrostomy catheter relieved the obstruction and significantly improved kidney function, successfully preventing progression to more advanced renal disease in these patients. (Source: Biology of Blood and Marrow Transplantation)

Symptomatic Parainfluenza Virus Infections in Children Undergoing Hematopoietic Stem Cell Transplantation

Biology of Blood and Marrow Transplantation — Thu, 10 Mar 2011 05:00:00 +0100

This study examined the incidence of symptomatic PIV infections, risk factors for lower respiratory tract infection (LRTI), and the impact on mortality after pediatric HSCT. A total of 1028 children who underwent HSCT between 1995 and 2009 were studied. PIV infections were detected in 46 of the 738 patients tested for respiratory infection (6.2%). PIV infection was the most common symptomatic respiratory viral infection in this population. On multivariate logistic regression analysis, receipt of an allogeneic transplant (P < .0001) and total body irradiation–based conditioning (P < .0001) were associated with increased risk of acquiring symptomatic PIV infection. Of the 46 HSCT patients with PIV infection, 18 (39%) had an LRTI. LRTI was associated with PIV infection in the first 100 days...

Blood, and Not Urine, BK Viral Load Predicts Renal Outcome in Children with Hemorrhagic Cystitis following Hematopoietic Stem Cell Transplantation

Biology of Blood and Marrow Transplantation — Mon, 07 Mar 2011 05:00:00 +0100

BK virus is a significant cause of hemorrhagic cystitis after hematopoietic stem cell transplantation (HSCT). However, its role in nephropathy post-HSCT is less studied. We retrospectively evaluated clinical outcomes in pediatric HSCT patients with hemorrhagic cystitis. Although most of these patients had very high urine BK viral loads (viruria), patients with higher BK plasma loads (viremia) had significant renal dysfunction, a worse clinical course, and decreased survival. Patients with a peak plasma BK viral load of >10,000 copies/mL (high viremia) were more likely to need dialysis and aggressive treatment for hemorrhagic cystitis compared to patients with ≤10,000 copies/mL (low viremia). Conversely, most patients with low viremia had only transient elevations in creatinine, and less ...

Fludarabine and Pharmacokinetic-Targeted Busulfan before Allografting for Adults with Acute Lymphoid Leukemia

Biology of Blood and Marrow Transplantation — Mon, 07 Mar 2011 05:00:00 +0100

We aimed to evaluate the safety and efficacy of fludarabine (FLU) and pharmacokinetic-targeted busulfan (BU) as conditioning regimen for hematopoietic cell transplantation (HCT) in adult patients with acute lymphoid leukemia (ALL). Forty-four patients with ALL (27 in first complete remission [CR1] and 17 in more advanced disease stage: 4 with primary induction failure [PIF], 12 in CR2, and 1 in CR3) received FLU and pharmacokinetic-targeted BU as preparative therapy for HCT. Grafts were T-replete, filgrastim-mobilized peripheral blood stem cells (PBSC). Graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus (TAC) and short-course methotrexate in 36 patients, TAC and sirolimus in 3, and TAC and mycophenolate mofetil in 5. Primary engraftment was achieved in all 44 patients. Th...

Ex Vivo T Cell Depletion of Allogeneic PBSC as Acute and Chronic GVHD Prophylaxis after Myeloablative HCT: Time to Reconsider?

Biology of Blood and Marrow Transplantation — Mon, 07 Mar 2011 00:00:00 +0100

Although established as an effective method for mitigating graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT), ex vivo donor T cell depletion (TCD) has yet to gain wide application. Randomized clinical trials to date have shown TCD reduces acute GVHD (aGVHD), but offers no survival advantage over conventional pharmacologic GVHD prophylaxis . The benefits of TCD in GVHD reduction were often counterbalanced by an increased risk of relapse, graft failure, posttransplant lymphoproliferative disease, and infections. Further, these studies primarily involved TCD of bone marrow grafts using inefficient and time-consuming antibody-based and/or mechanical separation techniques. The landscape of HCT has changed significantly over the past decade. More patients...

Relapse of Lymphoma after Allogeneic Hematopoietic Cell Transplantation: Management Strategies and Outcome

Biology of Blood and Marrow Transplantation — Mon, 21 Feb 2011 05:00:00 +0100

We describe the treatments, response, prognosis, and long-term survival of 72 patients with relapse of lymphoma after allogeneic HCT. Between 1991 and 2007, 227 lymphoma patients underwent allogeneic HCT. Of these, 72 (32%) developed relapse/progression after their HCT at a median of 99 days (0-1898 days); 37 had early (100 days) post-HCT. Three-year survival after HCT was significantly better in late than early relapse (53%; 95% confidence interval [CI] [34%-69%] versus 36%, [20%-52%], P = .02). Of 72 relapsed patients, 29 (40%) survived at a median of 34 (3-148) months posttransplant. The most common cause of death was underlying lymphoma (79%). The overall prognosis of relapsed/progressive lymphoma after allogeneic HCT is disappointing, yet half of patients respond to withdrawal of immu...

Myeloablative Reduced-Toxicity i.v. Busulfan-Fludarabine and Allogeneic Hematopoietic Stem Cell Transplant for Patients with Acute Myeloid Leukemia or Myelodysplastic Syndrome in the Sixth through Eighth Decades of Life

Biology of Blood and Marrow Transplantation — Mon, 21 Feb 2011 05:00:00 +0100

The optimal pretransplant regimen for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) in patients ≥55 years of age remains to be determined. The myeloablative reduced-toxicity 4-day regimen i.v. busulfan (Bu) (130 mg/m2) and i.v. fludarabine (Flu) (40 mg/m2) is associated with low morbidity and mortality. We analyzed 79 patients ≥55 years of age (median, 58 years) with AML (n = 63) or MDS (n = 16) treated with i.v. Bu-Flu conditioning regimens between 2001 and 2009 (median follow-up, 24 months). The patients who received this regimen had a good performance status. The 2-year overall survival (OS) rates for patients in first complete remission (CR1), second CR (CR2), or refractory disease and for all patients at time of transplantation were 71%, 44%, 32%, and 46%, respect...

High-Dose Therapy and Autologous Hematopoietic Cell Transplantation in Peripheral T Cell Lymphoma (PTCL): Analysis of Prognostic Factors

Biology of Blood and Marrow Transplantation — Mon, 21 Feb 2011 05:00:00 +0100

We examined the outcomes of high-dose therapy (HDT) and autologous hematopoietic cell transplant (AHCT) on the treatment of PTCL and the impact of patient/disease features on long-term outcome. Sixty-seven patients with PTCL–not otherwise specified (n = 30), anaplastic large cell lymphoma (n = 30), and angioimmunoblastic T cell lymphoma (n = 7) underwent HDT/AHCT at the City of Hope. The median age was 48 years (range: 5-78). Twelve were transplanted in first complete remission (1CR)/partial remission (PR) and 55 with relapsed or induction failure disease (RL/IF). With a median follow-up for surviving patients of 65.8 months (range: 24.5-216.0) the 5-year overall survival (OS) and progression-free survival (PFS) were 54% and 40%, respectively. The 5-year PFS was 75% for 1CR/PR compared t...

Risk Factors Associated with Kidney Injury and the Impact of Kidney Injury on Overall Survival in Pediatric Recipients Following Allogeneic Stem Cell Transplant

Biology of Blood and Marrow Transplantation — Mon, 21 Feb 2011 05:00:00 +0100

Pediatric allogeneic stem cell transplant (AlloSCT) patients are at substantial risk of developing kidney injury (KI), and KI contributes to transplant-related morbidity and mortality. We compared the estimated creatinine clearance (eCrCl) at 1, 3, 6, 9, and 12 months post-AlloSCT in 170 patients following reduced toxicity conditioning (RTC) versus myeloablative conditioning (MAC) to baseline. eCrCl was calculated using the Schwartz equation. Patients with ≥50% drop in eCrCl from the baseline were considered to have KI. Patients received tacrolimus and mycophenolate mofetil (MMF) for graft-versus-host disease (GVHD) prophylaxis. The logistic regression model was used for assessing risk factors for KI. Seventy-six patients (median age = 10.6 years) received RTC AlloSCT; 94 patients (medi...

Enhanced Immune Response after a Second Dose of an AS03-Adjuvanted H1N1 Influenza A Vaccine in Patients after Hematopoietic Stem Cell Transplantation

Biology of Blood and Marrow Transplantation — Mon, 14 Feb 2011 05:00:00 +0100

Seroconversion rates following influenza vaccination in patients with hematologic malignancies after hematopoietic stem cell transplantation (HSCT) are known to be lower compared to healthy adults. The aim of our diagnostic study was to determine the rate of seroconversion after 1 or 2 doses of a novel split virion, inactivated, AS03-adjuvanted pandemic H1N1 influenza vaccine (A/California/7/2009) in HSCT recipients (ClinicalTrials.gov Identifier: NCT01017172). Blood samples were taken before and 21 days after a first dose and 21 days after a second dose of the vaccine. Antibody (AB) titers were determined by hemagglutination inhibition assay. Seroconversion was defined by either an AB titer of ≤1:10 before and ≥1:40 after or ≥1:10 before and ≥4-fold increase in AB titer 21 days af...

Role of Allogeneic Transplantation for FLT3/ITD Acute Myeloid Leukemia: Outcomes from 133 Consecutive Newly Diagnosed Patients from a Single Institution

Biology of Blood and Marrow Transplantation — Mon, 14 Feb 2011 00:00:00 +0100

Acute myelogenous leukemia (AML) patients with FLT3/ITD mutations have an inferior survival compared to AML patients with wild-type (WT) FLT3, primarily because of an increased relapse rate. Allogeneic transplantation represents a postremission therapy that is effective at reducing the risk of relapse for many cases of poor-risk AML. Whether or not allogeneic transplantation in first complete remission (CR) can improve outcomes for patients with FLT3/ITD AML remains controversial. Our institution has adopted a policy of pursuing allogeneic transplantation, including the use of alternate donors, for FLT3/ITD AML patients in remission. As part of an instituional review board–approved study, we performed a review of the clinical data from November 1, 2004, to October 31, 2008, on all adult ...

Low Risk of Chronic Graft-versus-Host Disease and Relapse Associated with T Cell–Depleted Peripheral Blood Stem Cell Transplantation for Acute Myelogenous Leukemia in First Remission: Results of the Blood and Marrow Transplant Clinical Trials Network Protocol 0303

Biology of Blood and Marrow Transplantation — Mon, 14 Feb 2011 00:00:00 +0100

Graft-versus-host disease (GVHD) is most effectively prevented by ex vivo T cell depletion (TCD) of the allograft, but its role in the treatment of patients undergoing allogeneic hematopoietic cell transplantation (HCT) for acute myelogenous leukemia (AML) in complete remission (CR) remains unclear. We performed a phase 2 single-arm multicenter study to evaluate the role of TCD in AML patients in CR1 or CR2 up to age 65 years. The primary objective was to achieve a disease-free survival (DFS) rate of >75% at 6 months posttransplantation. A total of 44 patients with AML in CR1 (n = 37) or CR2 (n = 7) with a median age of 48.5 years (range, 21-59 years) received myeloablative chemotherapy and fractionated total body irradiation (1375 cGy) followed by immunomagnetically selected CD34-enriched...

Biology of Blood and Marrow Transplantation via MedWorm.com

Contents

Officers and Directors of ASBMT

Editorial Board

Purpose and Scope

New Hope for Mobilization Failures . . . Again

2012 BMT Tandem Meetings

The National Marrow Donor Program’s Symposium on Hematopoietic Cell Transplantation in 2020: A Health Care Resource and Infrastructure Assessment

NCI, NHLBI/PBMTC First International Conference on Late Effects after Pediatric Hematopoietic Cell Transplantation: Health-Related Quality of Life, Functional, and Neurocognitive Outcomes

My AML Cytogenetics Classification Scheme Is Better Than Yours

Table of Contents

Officers and Directors of ASBMT

Editorial Board

Masthead (Purpose and Scope)

A Phase I Study of Gemtuzumab Ozogamicin (GO) in Combination with Busulfan and Cyclophosphamide (Bu/Cy) and Allogeneic Stem Cell Transplantation in Children with Poor-Risk CD33+ AML: A New Targeted Immunochemotherapy Myeloablative Conditioning (MAC) Regimen

Dasatinib as Salvage Therapy for Steroid Refractory and Imatinib Resistant or Intolerant Sclerotic Chronic Graft-versus-Host Disease

Table of Contents

Officers and Directors of ASBMT

Editorial Board

Masthead

Comorbidities and Outcomes: Advancing the Field Comes at a Price

The Pretransplantation Serum Cytokine Profile in Allogeneic Stem Cell Recipients Differs from Healthy Individuals, and Various Profiles are Associated with Different Risks of Posttransplantation Complications

Identification of a Coordinated CD8 and CD4 T Cell Response Directed Against Mismatched HLA Class I Causing Severe Acute Graft-versus-Host Disease

T Cell and B Cell Immunity can be Reconstituted with Mismatched Hematopoietic Stem Cell Transplantation Without Alkylator Therapy in Artemis-Deficient Mice Using Anti-Natural Killer Cell Antibody and Photochemically Treated Sensitized Donor T Cells

Age and the Outcome of Allogeneic Hematopoietic Stem Cell Transplantation: Was Tacitus Wrong?

NCI, NHLBI/PBMTC First International Conference on Late Effects after Pediatric Hematopoietic Cell Transplantation: Endocrine Challenges—Thyroid Dysfunction, Growth Impairment, Bone Health, & Reproductive Risks

Reduced-Intensity Allogeneic Hematopoietic Transplantation Should Be Considered a Standard of Care for Older Patients with Acute Myeloid Leukemia

Plerixafor for Autologous Peripheral Blood Stem Cell Mobilization in Patients Previously Treated with Fludarabine or Lenalidomide

National Cancer Institute–National Heart, Lung and Blood Institute/Pediatric Blood and Marrow Transplant Consortium First International Consensus Conference on Late Effects After Pediatric Hematopoietic Cell Transplantation: Long-Term Organ Damage and Dysfunction

Table of Contents

Officers and Directors of ASBMT

Editorial Board

Masthead (Purpose and Scope)

Hydrodynamic Delivery of Human IL-15 cDNA Increases Murine Natural Killer Cell Recovery after Syngeneic Bone Marrow Transplantation

CIK: A Path to GVL without GVHD?

Host Basophils Are Dispensable for Induction of Donor T Helper 2 Cell Differentiation and Severity of Experimental Graft-versus-Host Disease

Dynamics of Cytomegalovirus (CMV) Plasma DNAemia in Initial and Recurrent Episodes of Active CMV Infection in the Allogeneic Stem Cell Transplantation Setting: Implications for Designing Preemptive Antiviral Therapy Strategies

Table of Contents

Officers and Directors of ASBMT

Editorial Board

Masthead (Purpose and Scope)

Stable Long-Term Pulmonary Function after Myeloablative Double Cord Blood Transplant

“Pet Negativity”—The New Goal of Cytoreductive Therapy in Hodgkin's Lymphoma?

Preparative Regimens and Ageism

The Doorstep to the Temple of Wisdom

Classifying Cytogenetics in Patients with Acute Myelogenous Leukemia in Complete Remission Undergoing Allogeneic Transplantation: A Center for International Blood and Marrow Transplant Research Study

Easy-to-Read Informed Consent Forms for Hematopoietic Cell Transplantation Clinical Trials

Decreased Serum Albumin as a Biomarker for Severe Acute Graft-versus-Host Disease after Reduced-Intensity Allogeneic Hematopoietic Cell Transplantation

Development and Validation of a Test Dose Strategy for Once-Daily i.v. Busulfan: Importance of Fixed Infusion Rate Dosing

Plerixafor Added to Chemotherapy Plus G-CSF Is Safe and Allows Adequate PBSC Collection in Predicted Poor Mobilizer Patients with Multiple Myeloma or Lymphoma

Reduced-Intensity Conditioning before Allogeneic Hematopoietic Stem Cell Transplantation in Patients Over 60 Years: A Report from the SFGM-TC

Genome-wide Profiling in AML Patients Relapsing after Allogeneic Hematopoietic Cell Transplantation

Table of Contents

Officers and Directors of ASBMT

Editorial Board

Masthead (Purpose and Scope)

Treatment of FLT3-ITD-Positive Acute Myeloid Leukemia Relapsing after Allogeneic Stem Cell Transplantation with Sorafenib

Donor Characteristics Affecting Graft Failure, Graft-versus-Host Disease, and Survival after Unrelated Donor Transplantation with Reduced-Intensity Conditioning for Hematologic Malignancies

Evaluation and Management of BK Virus-Associated Nephropathy Following Allogeneic Hematopoietic Cell Transplantation

Hematopoietic Stem Cells Survive Circulation Arrest and Reconstitute Hematopoiesis in Myeloablated Mice

Polymorphisms in CCR6 Are Associated with Chronic Graft-versus-Host Disease and Invasive Fungal Disease in Matched-Related Hematopoietic Stem Cell Transplantation

NCI, NHLBI First International Consensus Conference on Late Effects after Pediatric Hematopoietic Cell Transplantation: Etiology and Pathogenesis of Late Effects after HCT Performed in Childhood—Methodologic Challenges

Genetic Variations in the Mycophenolate Mofetil Target Enzyme Are Associated with Acute GVHD Risk after Related and Unrelated Hematopoietic Cell Transplantation

Double Reduced-Intensity Allogeneic Hematopoietic Stem Cell Transplantation: A Retrospective Study from the SFGM-TC

Tocilizumab for the Treatment of Steroid Refractory Graft-versus-Host Disease

Can G-CSF Cause Leukemia in Hematopoietic Stem Cell Donors?

Accurate Targeting of Daily Intravenous Busulfan with 8-Hour Blood Sampling in Hospitalized Adult Hematopoietic Cell Transplant Recipients

Idiotype Immunization Following High-Dose Therapy and Autologous Stem Cell Transplantation for Non-Hodgkin Lymphoma

EBMT Risk Score Predicts Outcome of Allogeneic Hematopoietic Stem Cell Transplantation in Patients Who Have Failed a Previous Transplantation Procedure

NCI, NHLBI First International Consensus Conference on Late Effects after Pediatric Hematopoietic Cell Transplantation: State of the Science, Future Directions

Effect of Early Posttransplantation Tacrolimus Concentration on the Development of Acute Graft-versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation from Unrelated Donors

The Hematopoietic Cell Transplantation-Specific Comorbidity Index Fails to Predict Outcomes in High-Risk AML Patients Undergoing Allogeneic Transplantation—Investigation of Potential Limitations of the Index

The Incidence of Veno-Occlusive Disease Following Allogeneic Hematopoietic Stem Cell Transplantation Has Diminished and the Outcome Improved over the Last Decade

Comparison of Reduced-Intensity Hematopoietic Cell Transplantation with Chemotherapy in Patients Age 60-70 Years with Acute Myelogenous Leukemia in First Remission

Outcomes of Patients Treated and One Human Leukocyte Antigen–Mismatched Related Compared with Matched Unrelated Donors

The Role of Anti-HLA Antibodies in Hematopoietic Stem Cell Transplantation

Limiting the Daily Total Nucleated Cell Dose of Cryopreserved Peripheral Blood Stem Cell Products for Autologous Transplantation Improves Infusion-Related Safety with No Adverse Impact on Hematopoietic Engraftment

Planning and Response to Radiation Exposures

Contents

Officers and Directors of ASBMT