Hematological Oncology via MedWorm.com

Acute coronary syndrome upon receiving carmustine infusion before autologous stem‐cell transplantation

Hematological Oncology — Fri, 27 Jan 2012 05:00:00 +0100

(Source: Hematological Oncology)

Tumour burden predicts treatment resistance in patients with early unfavourable or advanced stage Hodgkin lymphoma treated with ABVD and radiotherapy

Hematological Oncology — Mon, 23 Jan 2012 05:00:00 +0100

AbstractThe purpose of the work was to investigate the factors predicting early resistance to treatment in Hodgkin lymphoma. Many staging parameters, including relative tumour burden (rTB), were analysed in 246 patients with Hodgkin lymphoma in relation to early failure, that is, less than complete remission (i.e. partial response, null response or progression) or occurrence of early relapse, as clinical expressions of resistance to treatment. Patients with early unfavourable disease were 129 and were treated with four to six cycles of ABVD + involved field radiotherapy; 117 patients with advanced stage disease received six cycles of ABVD + optional irradiation to no more than two sites. The rTB was volumetrically measured through the evaluation of staging computed tomography for all the l...

Endoscopic ultrasonography in gastric lymphomas: appraisal on reliability in long‐term follow‐up

Hematological Oncology — Tue, 20 Dec 2011 05:00:00 +0100

In conclusion, EUS evaluation does not seem reliable in follow‐up management of high‐grade lymphomas, although it could have a great clinical impact in the management of MALT lymphoma. Copyright © 2011 John Wiley & Sons, Ltd. (Source: Hematological Oncology)

Clinical features of extranodal marginal zone lymphoma of mucosa‐associated lymphoid tissue

Hematological Oncology — Thu, 01 Dec 2011 05:00:00 +0100

AbstractWe newly diagnosed 131 patients with extranodal marginal zone lymphoma of mucosa‐associated lymphoid tissue lymphoma between 1998 and 2010. We retrospectively studied 124 patients for whom complete clinical data were available at presentation and who had minimally undergone tumour staging by physical examination, computed tomography (CT), bone marrow aspiration, and biopsy. A slight female predominance (men, 58; women, 66) was observed in the study population; the median age was 67 years. The primary locations at presentation were the stomach (38%), orbita (20%), lung (12%), intestinal tract (8%), thyroid gland (6%), others (14%), and unknown (2%). Seventy per cent of patients had localized disease. Of the 124 patients, 14 (11%) had lymph node involvement, and 5 (4%) had bone m...

Clinical manifestations of primary pulmonary extranodal marginal zone lymphoma of mucosa‐associated lymphoid tissue in Japanese population

Hematological Oncology — Thu, 01 Dec 2011 05:00:00 +0100

AbstractWe retrospectively analysed 16 cases of newly diagnosed pulmonary mucosa‐associated lymphoid tissue (MALT) lymphoma in the Japanese population. The disease was found on the basis of examination findings in 14 cases, and clinical manifestations in 2. According to the extensive staging procedure, four patients had concomitant gastric involvement. Primary treatment involved surgery alone in two patients; surgery followed by rituximab (R)‐containing chemotherapy in two; R‐containing chemotherapy alone in 11; and chemoradiotherapy without R in one. Over the median observation period of 28 months, disease progression was recorded in three patients, but all 16 patients were alive at the end of the observation period. One patient was treated with R alone and achieved partial remiss...

Double‐delayed intensification paediatric protocol without radiotherapy is an efficient treatment in adult lymphoblastic lymphoma

Hematological Oncology — Thu, 01 Dec 2011 05:00:00 +0100

We report here the feasibility of a double‐delayed intensification paediatric protocol in 12 adult LBL patients. There were no relapses and no deaths, with a median follow‐up of 4.7 years. Using the same protocol, overall survival was significantly longer in LBL patients versus ALL patients (100% vs 75%, p = 0.05). Overall tolerance was acceptable and better in ALL patients. We have shown the feasibility and the good results of using this paediatric protocol in LBL. Copyright © 2012 John Wiley & Sons, Ltd. (Source: Hematological Oncology)

Imatinib plasma trough levels in chronic myeloid leukaemia: results of a multicentre study CSTI571AIL11TGLIVEC

Hematological Oncology — Thu, 01 Dec 2011 05:00:00 +0100

In this study, IMPLs were analysed in 191 patients with CML and were compared with achievement of molecular and cytogenetic responses (CyR). IMPLs were also correlated with renal and hepatic dysfunction. Additionally, self‐reported adherence was monitored. The median and mean IMPLs were 994 ng/mL and 1070 ± 686 ng/mL, respectively, with 96 patients (50%) achieving plasma levels >1000 ng/mL. Self‐reported patient compliance was 98%. Patients who achieved a complete CyR (CCyR) had significantly higher IMPLs (1078 ± 545 ng/mL) than those without CyR (827 ± 323 ng/mL, p = 0.045). When grouped together, patients who achieved a CCyR or partial CyR had significantly higher IMPLs than patients who achieved a minimal CyR or did not achieve a CyR (1066 ng/mL vs ...

Real‐time PCR‐based analysis of BRAF V600E mutation in low and intermediate grade lymphomas confirms frequent occurrence in hairy cell leukaemia

Hematological Oncology — Thu, 01 Dec 2011 05:00:00 +0100

AbstractHairy cell leukaemia (HCL) is a rare type of B‐cell non‐Hodgkin lymphoma (B‐NHL), which is not known to be associated with any characteristic recurrent karyotypic abnormality. A recent study that used massively parallel whole exome sequencing identified an activating V600E mutation in BRAF, which appeared specific for HCL. Here, we confirm the specificity of BRAF V600E for HCL among low and intermediate grade B‐NHL and describe a real‐time polymerase chain reaction method for detecting this mutation in cases with low tumour burden. The V600E mutation does not appear to be associated with microsatellite instability, unlike the case in colorectal cancer. Thus, in conjunction with prior data, our results suggest incorporation of BRAF V600E mutation analysis in the diagnostic...

Postrelapse survival rate correlates with first‐line treatment strategy with thalidomide in patients with newly diagnosed multiple myeloma: a meta‐analysis

Hematological Oncology — Thu, 01 Dec 2011 05:00:00 +0100

In conclusion, thalidomide exposed upfront correlated with shorter PRS that partially compensated for prolonged initially PFS and resulted in no survival benefit when it is given as both induction pre‐autologous and maintenance post‐autologous stem cell transplantation; shorter PRS was not observed, and survival was improved when it is given only during maintenance phase following autologous stem cell transplantation in the patients with myeloma and who are eligible for transplant. Copyright © 2011 John Wiley & Sons, Ltd. (Source: Hematological Oncology)

Inhibition of poly(ADP‐ribose) polymerase (PARP) and ataxia telangiectasia mutated (ATM) on the chemosensitivity of mantle cell lymphoma to agents that induce DNA strand breaks

Hematological Oncology — Thu, 01 Dec 2011 05:00:00 +0100

AbstractThere is a high incidence of genomic aberration of ataxia telangiectasia mutated (ATM) and genes encoding proteins involved in the ATM pathway in mantle cell lymphoma (MCL). It has been shown that poly(ADP‐ribose) polymerase inhibitor (PARPi) strongly enhances the cytotoxicity of agents, causing single‐strand DNA breaks in cells with impaired homologous recombination repair. Here, we show that PARPi AG14361 potentiates the cytotoxicity induced by topotecan treatment in MCL cell lines, which was not dependent on either TP53 or CHEK2 status. Inhibition and/or knockdown of ATM and BRCA2 did not potentiate the cytotoxic effect of treatment with PARPi and topotecan. With loss of function of ATM, other kinases can still mediate activation of ATM substrates as demonstrated by continue...

Editorial Board Article

Hematological Oncology — Thu, 01 Dec 2011 05:00:00 +0100

No abstract is available for this article. (Source: Hematological Oncology)

Emergence of central nervous system myeloma in the era of novel agents

Hematological Oncology — Thu, 01 Sep 2011 04:00:00 +0100

AbstractAlthough multiple myeloma (MM) remains an incurable disease, considerable improvements in survival have been made with the introduction of autologous stem cell transplantation and new drugs. Central nervous system (CNS) MM is a rare complication associated with poor survival. Historically, CNS disease developed early in the course of MM; however recently, patients often present with CNS disease following multiple lines of therapy. It is hypothesized that exposure to novel agents (thalidomide, lenalidomide and bortezomib) changes the natural history of MM, increasing the lifetime risk of CNS disease. We analysed the baseline characteristics, treatment and outcome data of patients who presented with CNS MM at Peter MacCallum Cancer Centre between 2001 and 2010. Seven patients were id...

Hepatitis C virus and GBV‐C virus prevalence among patients with B‐cell lymphoma in different European regions: a case‐control study of the International Extranodal Lymphoma Study Group

Hematological Oncology — Thu, 01 Sep 2011 04:00:00 +0100

This study confirmed the existence of marked geographic differences in the prevalence of HCV in NHL but cannot provide any significant evidence for an association between HCV and/or GBV‐C and B‐cell NHLs. Copyright © 2011 John Wiley & Sons, Ltd. (Source: Hematological Oncology)

Successful administration of rituximab–bendamustine regimen in the relapse of Hodgkin lymphoma after autologous hemopoietic stem cell transplantation

Hematological Oncology — Thu, 01 Sep 2011 04:00:00 +0100

ConclusionsBased on our experience, bendamustine–rituximab salvage therapy can be a suitable option for the treatment of post‐transplant progression or relapse of HL. Copyright © 2011 John Wiley & Sons, Ltd. (Source: Hematological Oncology)

Serum free light chains in myeloma patients with an intact M protein by immunofixation: potential roles for response assessment and prognosis during induction therapy with novel agents

Hematological Oncology — Thu, 01 Sep 2011 04:00:00 +0100

AbstractThe ascertainment of serum free light chain (sFLC) levels has been shown to be valuable in screening for the presence of plasma cell dyscrasia as well as for baseline prognosis in newly diagnosed patients. For patients with amyloidosis and those with oligo‐secretory or non‐secretory multiple myeloma (MM), serial measurement of sFLC has also been shown to be valuable in monitoring disease status. However, in patients with a measureable, intact monoclonal protein by immunofixation (M protein), the serial measurement of sFLC remains undefined and is currently not recommended in professional guidelines. Herein, we provide data comparing sFLC with M protein as biomarkers of response in newly diagnosed patients with MM undergoing induction therapy with the novel agents thalidomide, l...

Cell of origin fails to predict survival in patients with diffuse large B‐cell lymphoma treated with autologous hematopoietic stem cell transplantation

Hematological Oncology — Thu, 01 Sep 2011 04:00:00 +0100

Variations in glutathione‐S‐transferase genes influence risk of chronic myeloid leukemia

Hematological Oncology — Thu, 01 Sep 2011 04:00:00 +0100

In this study, we investigated the possible association between GSTM1 and GSTT1 polymorphisms and susceptibility to chronic myeloid leukemia (CML) in a Turkish population. In a case‐control study, 106 CML patients and 190 healthy controls were evaluated for GSTM1 and GSTT1 polymorphisms. GSTM1 null (GSTM1‐) genotype frequencies in CML cases and controls were 45.3% and 42.6%, respectively. GSTT1 null (GSTT1‐) genotype frequencies were 44.3% and 18.4%, respectively. The frequency of the GSTT1‐ genotype among CML patients was significantly higher than in controls [odds ratio (OR) 3.53, 95% confidence interval (CI) 2.08‐6.00; P < 0.0001]. Individuals with the GSTM1‐ genotype did not have increased risk of CML [OR: 1.11; 95% CI: 0.69‐1.80; P = 0.714]. The combined GSTM1...

Issue Information

Hematological Oncology — Thu, 01 Sep 2011 04:00:00 +0100

(Source: Hematological Oncology)

Role of platelet‐derived growth factor‐AB in tumour growth and angiogenesis in relation with other angiogenic cytokines in multiple myeloma

Hematological Oncology — Thu, 01 Sep 2011 04:00:00 +0100

AbstractAngiogenesis is a complex process essential for the growth, invasion, and metastasis of various malignant tumours, including multiple myeloma (MM). Various angiogenic cytokines have been implicated in the angiogenic process. Among them, platelet‐derived growth factor‐AB (PDGF‐AB) has been reported to be a potent stimulator of angiogenesis in many solid tumours and haematological malignancies, including MM. The aim of the study was to investigate the relationship between PDGF‐AB, microvascular density (MVD), and various angiogenic cytokines, such as basic fibroblast growth factor (b‐FGF), angiogenin (ANG), and interleukin‐6 (IL‐6), in MM patients. Forty‐seven MM patients before treatment, 22 of whom were in plateau phase, were studied. We determined the serum levels ...

Epidermal growth factor receptor expression in acute myelogenous leukaemia is associated with clinical prognosis

Hematological Oncology — Mon, 22 Aug 2011 23:00:00 +0100

AbstractThe epidermal growth factor receptor (EGFR) family belongs to type I receptor tyrosine kinases. Overexpression or mutation of EGFR/ErbB1 gene has been detected in a large number of human solid tumours. According to some previous report, this gene is not expressed in hematological malignancies. However, two recent clinical case reports showed that erlotinib caused complete remission of acute myeloid leukaemia (AML)‐M1 in patients who had both AML‐M1 and non‐small‐cell lung cancer. These results are supported by preclinical studies in which EGFR tyrosine kinase inhibitors have anti‐proliferative effects on AML. These findings prompted us to determine whether EGFR is expressed in human AML, through a large‐scale screening of both leukaemic cell lines and clinical samples. ...

Immunophenotype distinction between acute promyelocytic leukaemia and CD15− CD34− HLA‐DR− acute myeloid leukaemia with nucleophosmin mutations

Hematological Oncology — Tue, 02 Aug 2011 23:00:00 +0100

In conclusion, CD110 and CD33 reactivity may be useful to distinguish APL from NPM‐mutated AML with CD15, CD34 and HLA‐DR negativity. Nevertheless, cytogenetic and molecular characterization is necessary to establish the accurate diagnosis of AML. Copyright © 2011 John Wiley & Sons, Ltd. (Source: Hematological Oncology)

Extracellular ATP induces CD44 shedding from macrophage‐like P388D1 cells via the P2X7 receptor

Hematological Oncology — Tue, 02 Aug 2011 23:00:00 +0100

AbstractThe P2X7 receptor (P2X7R) is a nucleotide receptor expressed predominantly on hemopoietic, bone, and epithelial cells. The P2X7R can be activated by extracellular ATP and induces the influx of calcium, releases cytokines, and participates in cell proliferation and apoptosis. CD44 is an adhesion molecule. The effects of CD44 include cell–cell and cell–matrix adhesion interactions, lymphocyte activation, and cell migration. Many studies have shown that P2X7R and CD44 play important roles in hematological malignancies, but no study exists regarding the relationship between P2X7R and CD44. In the present study, we characterized P388D1 cells for the surface expression of CD44 and analyzed ATP‐induced shedding. The data showed that P388D1 cells express CD44. Incubation of P388D1 ce...

Polymorphisms of VEGF, GSTM1 and GSTT1 genes in multiple myeloma risk

Hematological Oncology — Mon, 01 Aug 2011 23:00:00 +0100

(Source: Hematological Oncology)

Long‐term survival of a child with refractory anaplastic large cell lymphoma following therapy with an antisense oligonucleotide, topotecan, and vinblastine

Hematological Oncology — Mon, 01 Aug 2011 23:00:00 +0100

AbstractAnaplastic large cell lymphoma includes a subset of highly aggressive tumours and has a relapse rate of 30% at 2 years. Relapsed patients often have poor clinical outcome. The use of antisense oligonucleotides to down‐regulate Bcl‐2 protein can reverse chemotherapy resistance. The authors describe an 11‐year‐old boy with recurrent anaplastic large cell lymphoma who had received double high‐dose chemotherapy followed by autologous haematopoietic stem‐cell transplantation, had refractory disease and then had achieved long‐term remission with the use of an antisense oligonucleotides in combination with vinblastine and topotecan. Copyright © 2011 John Wiley & Sons, Ltd. (Source: Hematological Oncology)

Novel agents‐based regimens as induction treatment prior to autologous stem‐cell transplantation in newly diagnosed multiple myeloma: a meta‐analysis of randomized controlled trials

Hematological Oncology — Mon, 01 Aug 2011 23:00:00 +0100

Clinical significance and prognosis of MYC translocation in diffuse large B‐cell lymphoma

Hematological Oncology — Mon, 20 Jun 2011 23:00:00 +0100

AbstractRecent studies have suggested that chromosomal aberrations of the MYC gene locus indicate an unfavorable prognosis in diffuse large B‐cell lymphoma (DLBCL). However, there have been few reports on MYC translocation in Chinese patients. One hundred and six cases of DLBCLs were analyzed using interphase fluorescent in situ hybridization. Immunophenotyping analysis (CD20, CD3, CD10, Bcl‐6, Mum‐1) was also performed. MYC translocation was identified in 13 (12.3%) out of 106 cases. All MYC+ DLBCLs showed a non‐germinal center B‐cell type. MYC+ DLBCLs showed significantly poorer overall survival (OS) and progression‐free survival, with a median OS and progression‐free survival time of 4.7 and 3.2 months, respectively (p < 0.001). Multivariate analysis using a Cox p...

The effect of zinc sulfate in the prevention of high‐dose chemotherapy‐induced mucositis: a double‐blind, randomized, placebo‐controlled study

Hematological Oncology — Sun, 19 Jun 2011 23:00:00 +0100

In conclusion, Zinc sulfate did not have any clinical benefits in prevention or reduction of severity, and duration of high‐dose chemotherapy‐induced mucositis in patients undergoing HSCT. Copyright © 2011 John Wiley & Sons, Ltd. (Source: Hematological Oncology)

Cellular (FLICE) like inhibitory protein (cFLIP) expression in diffuse large B‐cell lymphoma identifies a poor prognostic subset, but fails to predict the molecular subtype

Hematological Oncology — Wed, 01 Jun 2011 23:00:00 +0100

AbstractImmunohistochemistry can sub‐classify diffuse large B‐cell lymphoma (DLBCL) into germinal centre B‐cell like (GCB) and non‐GCB subtypes. The latter consists predominately of the activated B‐cell like subgroup in which nuclear factor kappa‐B activation is its characteristic. Expression of cellular caspase 8 (FLICE)‐like inhibitory protein (cFLIP), a caspase 8 homologue, is regulated by nuclear factor kappa‐B signalling, and it is the main inhibitor of Fas ligand activated apoptosis. To determine if cFLIP expression was confined to non‐GCB subtype, we studied 66 cases of DLBCL. cFLIP expression showed no significant correlation to DLBCL subtypes (GCB or non‐GCB) but was associated with a worse clinical outcome. For cFLIP positive and negative patients, the five‐...

Clinical implications of acute myeloid leukemia presenting as myeloid sarcoma

Hematological Oncology — Wed, 01 Jun 2011 23:00:00 +0100

AbstractIn this retrospective study, we aim to analyze the characteristics, treatments, and overall survival of all patients presenting with isolated myeloid sarcoma (MS) or MS with concomitant acute myeloid leukemia (AML) compared with all patients with AML, treated during the same period. We identified patients with AML with or without MS at diagnosis, presenting to our medical center between the years 1990 and 2005. There was no statistically significant difference between the groups regarding gender, age, cytogenetic risk groups, rate of complete remission, number of cycles of chemotherapy needed to achieve complete remission, and rate of first relapse. The time to death in the MS group was not significantly different (p = 0.60) from the AML group, and radiotherapy did not affect t...

Antileukaemia effect of rapamycin alone or in combination with daunorubicin on ph+ acute lymphoblastic leukaemia cell line

Hematological Oncology — Tue, 31 May 2011 23:00:00 +0100

In this study, we aimed to assess the antileukemic activity of rapamycin (RAPA) (Sigma‐Aldrich Corporation, MO, USA), a mammalian target of rapamycin inhibitor, alone and in combination with daunorubicin (DNR) (Pharmacia & Upjohn Company, Germany) in a Ph+ acute lymphoblastic cell line SUP‐B15 and a primary Ph+ ALL sample in vitro. Here, we demonstrated that 50 nmol/L of RAPA significantly intensified the inhibition induced by DNR on both Ph+ ALL cell line and a primary Ph+ ALL sample. Notably, we reported that the consequence of DNR treatment induced the over expression of the componets of mammalian target of rapamycin signalling pathway, whereas RAPA effectively eliminated this deleterious side effect of DNR, which might enhance DNR's ability to kill drug‐resistant cancer. Th...

Repeated transfusions of autologous cytokine‐induced killer cells for treatment of haematological malignancies in elderly patients: a pilot clinical trial

Hematological Oncology — Tue, 31 May 2011 23:00:00 +0100

AbstractThe elderly population is susceptible to haematological malignancies, and these elderly patients are intolerant to cytotoxic drugs. Therefore, the exploration of a safe and reliable strategy exclusive of chemotherapy is critical in improving the prognosis of elderly patients with haematological malignancies. We evaluated the safety and the efficacy of autologous cytokine‐induced killer (CIK) cells combined with recombinant human interleukin 2 (rhIL‐2) in the treatment of haematological malignancies in elderly patients. Peripheral blood mononuclear cells were isolated from 20 elderly patients with haematological malignancies, then augmented by priming with interferon gamma, rhIL‐2 and CD3 monoclonal antibody. The autologous CIK cells (2–3 × 109) were transfused back to ...

Overexpression of apoptosis‐associated speck‐like protein in P388D1 murine lymphoma cells affects metastatic properties

Hematological Oncology — Tue, 31 May 2011 23:00:00 +0100

AbstractApoptosis‐associated speck‐like protein (ASC) is a bipartite adaptor molecule that participates in inflammation and apoptosis. ASC silencing has been observed in a significant proportion of human cancers. Here, we examined the role of ASC overexpression in the metastasis of the P388D1 murine lymphoma cell line to the liver, lung, spleen and kidney. First, we determined that the P388D1 cells express ASC. Then, ASC overexpression in P388D1 was achieved by transfecting pEGFP‐ASC‐C2 into the P388D1 cells. Furthermore, after the ASC‐overexpressing P388D1 cells were injected into DBA/2 mice through the vena caudalis, their metastasis to the lung and the liver was significantly reduced in the pEGFP‐ASC‐C2‐transfected group. These data indicate that ASC overexpression affec...

Langerhans cell histiocytosis with central nervous system involvement—complete response to 2‐chlorodeoxyadenosine after failure of tyrosine kinase inhibitor therapies with sorafenib and imatinib

Hematological Oncology — Tue, 31 May 2011 23:00:00 +0100

AbstractLangerhans cell histiocytosis (LCH) is rare in adults, and only a subset of these patients suffers from central nervous system (CNS) involvement. Hence, evidence‐based treatment recommendations are lacking. A case of a 20‐year‐old student with multisystem LCH and extensive CNS involvement is described, who showed a durable response to 2‐chlorodeoxyadenosine after prior therapies with the tyrosine kinase inhibitors sorafenib and imatinib. In accordance to the experiences provided by other case series, which are reviewed herein, 2‐chlorodeoxyadenosine can be considered an effective and safe option for adult LCH with CNS involvement. Copyright © 2011 John Wiley & Sons, Ltd. (Source: Hematological Oncology)

Tumour lysis syndrome in children: experience of last decade

Hematological Oncology — Tue, 31 May 2011 23:00:00 +0100

AbstractThe strategy against tumour lysis syndrome (TLS) had been hyperhydration, urine alkalinization, and allopurinol. Recently, rasburicase was added to the armament against this life‐threatening condition. In Korea, rasburicase is used as a rescue therapy for cases with allopurinol‐resistant hyperuricemia, because of the restriction by the National Health Insurance. We reviewed our experiences to re‐assess the risk factors of TLS and the efficacy of rasburicase. Medical records were retrospectively reviewed for 396 children who were diagnosed as positive with acute leukemia and non‐Hodgkin lymphoma between the years 2000 and 2009. The risk factors for TLS were analyzed statistically, and those before and after the availability of rasburicase were compared. Sixty eight patients ...

Stevens–Johnson syndrome after lenalidomide therapy for multiple myeloma: a case report and a review of treatment options

Hematological Oncology — Tue, 31 May 2011 23:00:00 +0100

AbstractStevens‐ Johnson syndrome (SJS) is a severe and life‐threatening condition. Although allopurinol, an antihyperuricemia drug, is the drug most commonly associated with SJS, more than 100 different causative drugs have been reported. Among hematologic drugs recently introduced into the market, drugs such as rituximab, imatinib, and bortezomib are reported. Here, we describe a patient with SJS while receiving lenalidomide in combination with prednisolone for treatment‐naïve multiple myeloma. Although SJS has been reported rarely as an adverse reaction to Lenalidomide, this drug should be considered in the etiology of SJS, and the increased number of prescriptions of Lenalidomide for the therapy of multiple myeloma has to stress the awareness of its potentially serious side‐ef...

Clinical course of patients with aplastic anemia or myelodysplastic syndrome associated with persistent neutropenia

Hematological Oncology — Tue, 31 May 2011 23:00:00 +0100

In conclusion, severe neutropenia was significantly associated with IE in patients with AA or MDS, and IE might be lethal. When we only considered patients with MDS, the neutrophil count alone could not be used to predict the prognosis. Copyright © 2011 John Wiley & Sons, Ltd. (Source: Hematological Oncology)

Issue Information

Hematological Oncology — Tue, 31 May 2011 23:00:00 +0100

(Source: Hematological Oncology)

Azacitidine has limited activity in ‘real life’ patients with MDS and AML: a single centre experience

Hematological Oncology — Tue, 08 Mar 2011 00:00:00 +0100

AbstractMyelodysplastic syndrome (MDS) represents a heterogeneous group of potentially malignant diseases of bone‐marrow stem cells. Acute myelogenous leukaemia (AML) is an inevitable outcome for many patients with MDS. Azacitidine has been reported to result in comparably higher response rates and improved survival than other treatment strategies. In this retrospective study, we report the results on 25 ‘real life’ patients with MDS, CMML or AML treated with azacitidine between 2005 and 2009. All patients fulfilled the World Health Organization criteria for MDS and AML. No eligibility criteria other than diagnosis were considered. Complete response (CR) rate was observed in three of the 25 ‘real life’ patients (12%) with a median duration of CR of 5 months (4–6 months). Seven ...

Disease patterns in pediatric classical Hodgkin lymphoma: a report from a developing area in Brazil

Hematological Oncology — Fri, 04 Mar 2011 00:00:00 +0100

AbstractEpidemiological patterns established about 20 years ago, divided classical Hodgkin lymphoma (cHL) in three entities with regard to Epstein–Barr virus (EBV) status and histological subtypes and suggested different epidemiological patterns associated with degree of economic development. Here, we investigated histopathological features and EBV association in 100 consecutive pediatric cHL cases occurring in Rio de Janeiro (Brazil). Age at diagnosis ranged from 3 to 18 years (median 14 years) with 27% of cases ≤10 years. Unexpectedly, we did not observe an early childhood peak with most cases occurring in the >10 years age group. Nodular sclerosis (NS) was the most frequent subtype (69%) and was more frequently observed in the >10 years age group, followed by mixed cellularity...

Del(13q14.3) length matters: an integrated analysis of genomic, fluorescence in situ hybridization and clinical data in 169 chronic lymphocytic leukaemia patients with 13q deletion alone or a normal karyotype

Hematological Oncology — Tue, 01 Mar 2011 00:00:00 +0100

(Source: Hematological Oncology)

Metabolism of thalidomide by human liver microsome cytochrome CYP2C19 is required for its antimyeloma and antiangiogenic activities in vitro

Hematological Oncology — Tue, 01 Mar 2011 00:00:00 +0100

In this study, we used a system of human liver microsomes to investigate the antimyeloma and antiangiogenic activities of thalidomide. Myeloma cells and human umbilical vein endothelial cells (HUVECs) were treated with thalidomide alone or thalidomide incubated with human liver microsomal protein. We found that thalidomide alone had no direct effect on several multiple myeloma cell lines (U266, NCI‐H929, RPMI 8226, LP‐1, CZ‐1) or on HUVECs in vitro. However, when incubated with human liver microsomal protein, thalidomide (100 µg/ml) caused a decrease of 34.9–46.7% in cell viability in myeloma cells and 12% in HUVECs. Cell cycle analysis and apoptosis detection indicated that the decreases in cell viability were correlated with the induction of apoptosis. Thalidomide incubated wi...

FAME, a novel conditioning regimen for allogeneic stem cell transplantation for lymphoma, does not earn fame

Hematological Oncology — Tue, 01 Mar 2011 00:00:00 +0100

(Source: Hematological Oncology)

In situ follicular lymphoma: pathologic characteristics and diagnostic features

Hematological Oncology — Tue, 01 Mar 2011 00:00:00 +0100

AbstractThe diagnosis of in situ follicular lymphoma (FL) is feasible when immunohistochemical characterization is carried out and genetic abnormalities are assessed. We usually use a selected diagnostic panel of antibodies (CD10, CD20, CD23, BCL2, BCL6, and Ki67) in lymph nodes with follicular hyperplasia only when we analyze an unexplained lymphadenopathy. Molecular studies, for example, fluorescence in situ hybridization analysis for t(14;18), are restricted to doubtful cases in which immunohistochemistry data are ambiguous. Immunohistochemically, the involved follicles show strongly positive staining for BCL2 and CD10. The BCL2+ cells are confined only to germinal centers and are not seen in the interfollicular region or elsewhere in the lymph node. The BCL2 staining in the abnormal fo...

Effects of second‐generation tyrosine kinase inhibitors towards osteogenic differentiation of human mesenchymal cells of healthy donors

Hematological Oncology — Tue, 01 Mar 2011 00:00:00 +0100

In conclusion, we show that besides imatinib, other tyrosine kinase inhibitors (TKIs) such as dasatinib and nilotinib, but not bosutinib, increase osteogenic markers in hBM‐MSCs. Because bosutinib differs from the other TKIs because of its low affinity to other kinases such as PDGF‐R, these experiments suggest that inhibition of PDGF‐R may be involved in the induction of osteoblastogenesis by TKIs. Copyright © 2011 John Wiley & Sons, Ltd. (Source: Hematological Oncology)

Minimal residual disease detection in lymphoma and multiple myeloma: impact on therapeutic paradigms

Hematological Oncology — Tue, 01 Mar 2011 00:00:00 +0100

AbstractEarly identification of patients at high risk of relapse is a major goal of current translational research in oncohematology. Minimal residual disease (MRD) detection by polymerase chain reaction‐based methods is currently part of the routine clinical management of patients with acute lymphoblastic leukemia. However, the current knowledge indicates that it is also a useful prognostic tool in several mature lymphoproliferative disorders. Its utility is currently well established in follicular lymphoma, mantle cell lymphoma, and multiple myeloma. In some of these entities, clinical trials employing MRD as a decision‐making tool are currently ongoing. In the present review, we will discuss the ‘state of the art’ of MRD evaluation in these three neoplasms with the ultimate aim ...

In vitro efficacy of tyrosine kinase inhibitors: SYK and BCR‐ABL inhibitors in lymphomas

Hematological Oncology — Tue, 01 Mar 2011 00:00:00 +0100

(Source: Hematological Oncology)

FLT3 mutation and expression did not adversely affect clinical outcome of childhood acute leukaemia—a study of 531 Southeast Asian children by the Ma‐Spore study group

Hematological Oncology — Tue, 01 Mar 2011 00:00:00 +0100

AbstractFMS‐like tyrosine kinase 3 (FLT3) is critical for normal haematopoiesis and have been reported to be expressed in the majority of acute myeloid and lymphoid malignancies. We correlated the impact of FLT3 mutations and its expression with age, WHO 2008 classification and treatment outcome in 531 childhood acute leukaemias. Of 150 acute myeloid leukaemia (AMLs), 18 (12%) harboured FLT3‐ITD while nine (6%) had FLT3‐TKD. FLT3‐ITD and ‐TKD were rare in acute megakaryoblastic leukaemia (AMKL; FLT3‐ITD 0/26, FLT3‐TKD 1/26) and children below 3 years (n = 2/48). Acute promyelocytic leukaemia (APL) with t(15;17);PML‐RARα (n = 7/18; 39%) harboured the highest frequency of FLT3 mutations, followed by myelomonocytic (n = 4/18; 22%) and AML with t(8;21);RUNX1‐RU...

Cancer and its management, sixth edition. Jeffrey Tobias and Daniel Hochhauser. Wiley‐Blackwell, Chichester, UK, 2010, Paperback edition, 560pp., ISBN 978‐1‐4051‐7015‐4.

Hematological Oncology — Tue, 01 Mar 2011 00:00:00 +0100

(Source: Hematological Oncology)

Issue Information

Hematological Oncology — Tue, 01 Mar 2011 00:00:00 +0100

(Source: Hematological Oncology)

Higher busulfan dose intensity does not improve outcomes of patients undergoing allogeneic haematopoietic cell transplantation following fludarabine, busulfan‐based reduced toxicity conditioning

Hematological Oncology — Mon, 28 Feb 2011 00:00:00 +0100

AbstractWe evaluated the impact of busulfan dose intensity in patients undergoing reduced toxicity/intensity conditioning allogeneic transplantation in a multicenter retrospective study of 112 consecutive patients. Seventy‐five patients were conditioned with busulfan (0.8 mg/kg/dose IV × 8 doses), fludarabine (30 mg/m2/day, days −7 to −3), and 6 mg/kg of ATG [reduced intensity conditioning (RIC) group], while 37 patients received a more‐intense conditioning with busulfan (130 mg/m2/day IV, days −6 to −3), fludarabine (40 mg/m2/day, days −6 to −3) and 6 mg/kg of ATG [reduced toxicity conditioning (RTC) group]. At baseline both groups were matched for median age, unrelated donor allografts, and human leukocyte antigen‐mismatched allografts. More patients in...

Intrapericardial steroid treatment for recurrent pericardial effusion in a patient with acute lymphoblastic Leukaemia

Hematological Oncology — Wed, 09 Feb 2011 00:00:00 +0100

AbstractIntrapericardial corticosteroid therapy for pericardial effusion is an uncommon practice. We had an initial experience with this therapeutic measure but this was our first attempt in the context of malignant diseases and paraneoplastic syndrome. A patient with relapsed Acute Lymphoblastic Leukemia and recurrent pericardial effusion presented. She had been treated by pericardiocenthesis and systemic corticosteroids on two occasions. Following the second pericardiocenthesis and pericardial drainage, methylprednisolone was injected into the pericardium prior to withdrawal of the draining catheter. The patient had a dramatic clinical improvement with a short hospital stay and a lower dose of systemic steroids. We conclude that Intrapericardial steroids injection may be beneficial for p...

Pegfilgrastim primary prophylaxis in patients with non‐Hodgkin lymphoma: results from an integrated analysis

Hematological Oncology — Tue, 18 Jan 2011 00:00:00 +0100

AbstractSevere neutropenia and febrile neutropenia (FN) are serious, dose‐limiting side effects of chemotherapy for aggressive non‐Hodgkin lymphoma (NHL). Observational data suggest that with current practice neutropenia management up to 23% of patients receiving CHOP‐like regimens experience FN, and around half of patients do not receive the planned relative dose intensity (RDI). In this integrated analysis we assessed the efficacy of pegfilgrastim for preventing FN and related outcomes in patients with NHL. A literature search was used to identify chemotherapy regimens with an FN risk ≥15% that are used to treat lymphoma. Search results were then used to identify clinical trials in which these regimens were administered with pegfilgrastim primary prophylaxis. Individual patient d...

Derivative (1;7)(q10;p10) in two patients with myelodysplastic syndrome after autologous haematopoietic cell transplantation

Hematological Oncology — Mon, 20 Dec 2010 00:00:00 +0100

(Source: Hematological Oncology)

Bone marrow donation perceptions among healthcare workers: a survey at University of Toledo Medical Center

Hematological Oncology — Thu, 16 Dec 2010 00:00:00 +0100

(Source: Hematological Oncology)

Addendum to Hematological Oncology vol. 27, supplement 1

Hematological Oncology — Wed, 01 Dec 2010 00:00:00 +0100

(Source: Hematological Oncology)

A review of the trends of lymphomas in the equatorial belt of Africa

Hematological Oncology — Tue, 30 Nov 2010 00:00:00 +0100

AbstractLymphomas represent one of the most frequent cancer types in Africa. In particular, approximately 30 000 non‐Hodgkin lymphomas occur in the equatorial belt of Africa each year and these tumours are in among the top‐ten cancers in this geographical region. Several pathogens and environmental factors have been detected in association with these tumours, suggesting that they may contribute to lymphomagenesis. Unfortunately, there are still striking differences between developed and African countries in terms of early detection, diagnosis and treatment of lymphomas. Of note, the disease burden appears to be increasing in Africa. In addition, a much lower cure rate in the low‐income countries suggests that the difference in mortality will even become more pronounced in future. T...

Comparison of fixed dose pegfilgrastim and daily filgrastim after autologous stem cell transplantation in patients with multiple myeloma autografted on a outpatient basis

Hematological Oncology — Tue, 30 Nov 2010 00:00:00 +0100

In conclusion, ASCT on an outpatient basis is feasible and safe in patients with MM, the majority of whom are manageable at home. The administration of single dose PEG results in no different outcome in terms of safety and efficacy as compared to 8 days of G‐CSF. Copyright © 2010 John Wiley & Sons, Ltd. (Source: Hematological Oncology)

Hairy cell leukaemia: biological and clinical overview from immunogenetic insights

Hematological Oncology — Wed, 01 Sep 2010 00:00:00 +0100

AbstractHairy cell Leukaemia (HCL) is a rare neoplasm of peripheral B cells which represents a paradox in oncology. Despite its largely unknown origin and behaviour, HCL is one of the few example of dramatic success in the treatment of a malignancy. The recent steps forward to understanding the biology of HCL from immunogenetic and genomic studies have recently provided new insight into diagnosis and prognosis. Several data from immunoglobulin gene (IG) analysis have provided hints regarding the cell of origin and the ongoing selective interactions of the tumour BCR with environmental stimuli. It has also recently emerged that an unmutated status of the HCL IG can be associated with failure to respond to cladribine, genetic abnormalities indicative of poor outcome and aggressive disease. T...

Impact of TET2 mutations on mRNA expression and clinical outcomes in MDS patients treated with DNA methyltransferase inhibitors

Hematological Oncology — Tue, 31 Aug 2010 23:00:00 +0100

(Source: Hematological Oncology)

A preliminary experience with the HyperCHiDAM Verona intensive chemotherapy regimen in heavily pretreated refractory Hodgkin's lymphoma

Hematological Oncology — Tue, 31 Aug 2010 23:00:00 +0100

Abstract (Source: Hematological Oncology)

Follicular lymphoma at relapse after rituximab containing regimens: comparison of time to event intervals prior to and after 90Y‐ibritumomab‐tiuxetan

Hematological Oncology — Tue, 31 Aug 2010 23:00:00 +0100

Abstract (Source: Hematological Oncology)

Bone Marrow Pathology, fourth edition. Barbara Bain, David M. Clark and Bridget S. Wilkins. Wiley‐Blackwell, Chichester, UK, January 2010, Hardcover edition, 630pp. ISBN: 9781405168250

Hematological Oncology — Tue, 31 Aug 2010 23:00:00 +0100

(Source: Hematological Oncology)

Cytogenetic abnormalities in reactive lymphoid hyperplasia: byproducts of the germinal centre reaction or indicators of lymphoma?

Hematological Oncology — Wed, 04 Aug 2010 23:00:00 +0100

Non-random karyotypic abnormalities associated with non-Hodgkin lymphomas (NHLs) have been described in cases of reactive lymphoid hyperplasia (RLH). However, the frequency and types of cytogenetic aberrations detected and their clinical relevance are unknown. To address these questions, we undertook a retrospective analysis of a large series of RLH diagnosed at our institute over 8 years. Cytogenetic abnormalities were identified in 20 of 116 (17%) cases with informative karyotypes, comprising 14 (70%) structural and 11 (55%) numerical changes. Clonal (n = 14, 70%) and non-clonal (n = 6, 30%) abnormalities were observed. Aberrations of chromosome 14 were the most frequent (n = 8, 42%, 7 represented IgH translocations), followed by chromosome 3 (n = 4, 3 represented BCL6 translocations), a...

Relevance of a scoring system including CD11c expression in the identification of splenic diffuse red pulp small B-cell lymphoma (SRPL)

Hematological Oncology — Fri, 30 Jul 2010 23:00:00 +0100

'Splenic red pulp lymphoma with numerous basophilic villous lymphocytes' (SRPL), recently described, is characterized by clinical, morphologic, immunologic, cytogenetic and molecular features distinct from SMZL/SLVL and HCL. In particular, the intensity of CD11c staining (expressed as fluorescence intensity -RFI-) in SRPL is significantly different from the RFI in SMZL/SLVL and HCL. Moreover the use of a scoring system based on the expression of CD11c, CD22, CD76, CD38 and CD27 appears to improve the differential diagnosis between SRPL and SMZL/SLVL and emphasizes that SRPL is an entity closed to but distinct from SMZL/SLVL. Copyright © 2010 John Wiley & Sons, Ltd. (Source: Hematological Oncology)

Multicentre validation of a prognostic index for overall survival in chronic lymphocytic leukaemia

Hematological Oncology — Thu, 29 Jul 2010 23:00:00 +0100

We wish to validate in a multicentric CLL population a nomogram and a risk score recently developed to predict overall survival (OS). Complete records from 1037 CLL patients were retrospectively collected to estimate OS and time to treatment (TTT). Cox models were used to test the independence of age, [beta]-2-microglobulin, absolute lymphocyte count (ALC), sex, Rai stage and number of involved lymph node regions (LNR). Accuracy of prognostic models was tested with the concordance index (c-index). Median follow-up was 5.5 years, with 151 deaths and 475 treated patients. Median OS was not reached (65% survival rate at 13.9 years), median TTT was 6 years. We confirmed the ability of the prognostic score to predict OS and TTT in three risk groups, with results comparable with those reported i...

Lack of allelic exclusion by secondary rearrangements of tumour B-cell receptor light chains in hairy cell leukaemia

Hematological Oncology — Fri, 23 Jul 2010 23:00:00 +0100

Analyses of the tumour immunoglobulin (Ig) gene (IG) heavy (H) and light chains show heterogeneity of mutational status, but reveal common features of ongoing IGH isotype-switching with multiple IGH isotype expression and preference of IG lambda (IGL) light chain with selective use of IGLJ3. Phenotypic and immunogenetic analyses were performed in a series of 105 HCL patients to estimate prevalence of multiple IG light chain expression by the tumour cells. By phenotype, 3/105 HCL (2.9%) expressed double tumour-related Ig kappa (K) and L light chain proteins. By immunogenetic analysis, functional mutated double IGKI/IGKII, IGKI/IGLI and IGLI/IGLII transcripts were cloned and sequenced in 3/71 (4.2%) HCL. These latter three HCL expressed multiple IGH isotypes with mutated IGHVDJ rearrangement...

Variation in innate immunity genes and risk of multiple myeloma

Hematological Oncology — Thu, 22 Jul 2010 23:00:00 +0100

Multiple myeloma (MM) is a B-cell lymphoid malignancy suspected to be associated with immunologic factors. Given recent findings associating single-nucleotide polymorphisms (SNPs) in innate immunity genes with non-Hodgkin lymphoma, we conducted an investigation of innate immune gene variants using specimens from a population-based case-control study of MM conducted in Connecticut women. Tag SNPs (N = 1461) summarizing common variation in 149 gene regions were genotyped in non-Hispanic Caucasian subjects (103 cases, 475 controls). Odds ratios (OR) and 95% confidence intervals (CI) relating SNP associations with MM were computed using unconditional logistic regression, while the MinP test was used to investigate associations with MM at the gene level. We calculated permutation-adjusted P-val...

Diffuse large B-cell lymphoma with concordant bone marrow involvement has peculiar genomic profile and poor clinical outcome

Hematological Oncology — Thu, 15 Jul 2010 23:00:00 +0100

Bone marrow (BM) involvement in diffuse large B-cell lymphoma (DLBCL) can be morphologically discordant from the primary tumor. Concordant BM infiltration has been shown associated with a poorer outcome in patients treated with CHOP. In order to evaluate tumor-related factors leading to BM involvement in DLBCL, we performed an integrated analysis of i) genomic profiles obtained with a high-density genome wide SNP-based arrays ii) immunomorphological and iii) clinical data from 133 patients uniformly treated with R-CHOP. BM infiltration was found in 27 of 133 (20%) cases; and it was concordant in 18/27 (67%) cases. Concordant infiltration, but not discordant, influenced negatively OS, PFS and DFS and was associated with higher serum LDH, lower CR and higher PD rates. No association with cel...

The prevalence and clinical significance of 18F-2-fluoro-2-deoxy-D-glucose (FDG) uptake in the thyroid gland on PET or PET-CT in patients with lymphoma

Hematological Oncology — Wed, 14 Jul 2010 23:00:00 +0100

F18-2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) has become a well established tool in staging and assessing therapy response in lymphoma. Incidental thyroid uptake on PET is not uncommon and can pose a diagnostic and management challenge. We retrospectively evaluate the prevalence and clinical significance of incidental FDG uptake in the thyroid gland in patients with lymphoma. 1868 lymphoma patients underwent PET and PET-CT between August 2002 and August 2008. 52 patients (2.8%) demonstrated FDG thyroid uptake (M = 17, F = 35; mean age 63 yr). Thyroid uptake was determined as focal or diffuse, maximum standardized uptake values (SUVmax) recorded as well as SUV max ratio compared to background mediastinum activity (SUVR). Corresponding CT findings on PET-CT were eva...

LACE-conditioned autologous stem cell transplantation for relapsed or refractory diffuse large B-cell lymphoma: treatment outcome and risk factor analysis from a single centre

Hematological Oncology — Tue, 13 Jul 2010 23:00:00 +0100

High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is a recognized treatment option for patients with relapsed diffuse large B-cell lymphoma. We have analysed 51 patients who underwent ASCT after LACE (lomustine (CCNU), cytarabine (Ara-C), cyclophosphamide, etoposide) conditioning for relapsed (n = 34, 67%) or primary refractory (n = 17, 33%) diffuse large B-cell lymphoma. With a median follow-up of 60 months (range 2-216) the probabilities of overall survival (OS) and progression-free survival (PFS) at 5 years were 47 and 42%, respectively. The cumulative treatment-related mortality was 10% (n = 5). Probabilities for OS and PFS at 5 years were 56 and 50% for patients with chemosensitive and 29 and 27% for patients with chemorefractory disease. In multivariate a...

ROR1 expression is not a unique marker of CLL

Hematological Oncology — Thu, 01 Jul 2010 23:00:00 +0100

Recent studies have identified receptor tyrosine kinase-like orphan receptor 1 (ROR1) on the surface of chronic lymphoid leukaemia (CLL) cells. In order to determine whether ROR1 expression is a suitable surrogate marker for the diagnosis of CLL we analysed the mRNA level of ROR1 in different types of non-Hodgkin lymphomas (NHL), and detected elevated levels of ROR1 compared to control peripheral mononuclear cells in several entities (CLL [ge] mantle cell lymphoma (MCL) > marginal zone lymphoma (MZL) >> diffuse large B-cell lymphoma > follicular lymphoma). ROR1 protein was expressed intensely on the cell surface of lymphoma cells with leukaemic blood count detected by three colour immunofluorescence. Our results indicate that ROR1 expression is not limited to CLL cases, but it is more prev...

Reply to Z. Blumenfeld

Hematological Oncology — Thu, 24 Jun 2010 23:00:00 +0100

No Abstract. (Source: Hematological Oncology)

Reduced-intensity conditioning allogeneic transplant in heavily pre-treated chronic lymphocytic leukaemia patients: a single centre experience

Hematological Oncology — Sun, 20 Jun 2010 23:00:00 +0100

No Abstract. (Source: Hematological Oncology)

Immune reconstitution of B-cell lymphoma patients receiving CHOP-based chemotherapy containing rituximab

Hematological Oncology — Mon, 14 Jun 2010 23:00:00 +0100

Sixty-six B-cell lymphoma patients were treated with a CHOP-based chemotherapy containing rituximab (R-CHOP-like regimen). Immune reconstitution was assessed by measuring lymphocyte subsets and immunoglobulins. Fifty-five patients (83.3%) underwent six cycles of the R-CHOP-like regimen. CD19+ and CD20+ cells were completely eliminated from the peripheral blood after one cycle of the R-CHOP-like regimen; they were detected again 6 months after the therapy. One year after the therapy, B-cell numbers recovered to their level at diagnosis and almost doubled 2 years after the therapy. The lowest numbers of CD3+, CD8+ and CD56+ cells were seen after three cycles of the regimen, but continued to increase until 1 year after the therapy, remaining stable thereafter. CD4+ T-cells were at their lowes...

Fertility preservation after chemotherapy for Hodgkin lymphoma

Hematological Oncology — Wed, 09 Jun 2010 23:00:00 +0100

No Abstract. (Source: Hematological Oncology)

The effect of allogeneic stem cell transplantation on high risk chronic lymphocytic leukaemia: a single centre retrospective analysis

Hematological Oncology — Wed, 09 Jun 2010 23:00:00 +0100

In recent years, many studies have confirmed that allogeneic stem cell transplantation (allo-SCT) can provide long-term disease control and possible cure in selected patients with chronic lymphocytic leukaemia (CLL), including those with a biologically highly unfavourable risk profile. A retrospective analysis of allo-SCT in 30 patients with CLL whose risk profile was unfavourable and who were treated in the years 2000-2009 was performed. The aim was to compare the results of allo-SCT by prognostic factors and conditioning type and evaluate the results of unrelated transplantation. The median age was 54 years. Donors were 8 HLA-matched siblings and 22 unrelated volunteers, 11 of whom were mismatched. Eighteen patients were treated with reduced intensity conditioning. Twelve patients receiv...

Epidemiology and management of lymphoma in low-income countries

Hematological Oncology — Mon, 07 Jun 2010 23:00:00 +0100

Transient monoclonal CD3+ T large granular lymphocyte proliferation in a case of mantle cell lymphoma with Rituximab‐associated late onset neutropenia

Hematological Oncology — Mon, 31 May 2010 23:00:00 +0100

(Source: Hematological Oncology)

Xenobiotic and folate pathway gene polymorphisms and risk of childhood acute lymphoblastic leukaemia in Javanese children

Hematological Oncology — Mon, 31 May 2010 23:00:00 +0100

Abstract (Source: Hematological Oncology)

Secondary hemophagocytic syndrome in adults: a case series of 18 patients in a single institution and a review of literature

Hematological Oncology — Mon, 31 May 2010 23:00:00 +0100

(Source: Hematological Oncology)

Experimental and clinical characteristics in myelodysplastic syndrome patients with or without HLA‐DR15 allele

Hematological Oncology — Mon, 31 May 2010 23:00:00 +0100

Abstract (Source: Hematological Oncology)

Clinical characteristics of patients with chronic eosinophilic leukaemia (CEL) harbouring FIP1L1‐PDGFRA fusion transcript—results of Polish multicentre study

Hematological Oncology — Mon, 31 May 2010 23:00:00 +0100

Abstract (Source: Hematological Oncology)

Dynamic change of T315I BCR‐ABL kinase domain mutation in Korean chronic myeloid leukaemia patients during treatment with Abl tyrosine kinase inhibitors

Hematological Oncology — Mon, 31 May 2010 23:00:00 +0100

Abstract (Source: Hematological Oncology)

CT‐guided percutaneous lung biopsies in patients with haematologic malignancies and undiagnosed pulmonary lesions

Hematological Oncology — Mon, 31 May 2010 23:00:00 +0100

Abstract (Source: Hematological Oncology)

Multicentre phase II study of CyclOBEAP plus rituximab in patients with diffuse large B‐cell lymphoma

Hematological Oncology — Mon, 31 May 2010 23:00:00 +0100

Abstract (Source: Hematological Oncology)

Genomic profiling of Richter's syndrome: recurrent lesions and differences with de novo diffuse large B‐cell lymphomas

Hematological Oncology — Mon, 31 May 2010 23:00:00 +0100

Abstract (Source: Hematological Oncology)

18F‐FDG uptake and its clinical relevance in primary gastric lymphoma

Hematological Oncology — Mon, 31 May 2010 23:00:00 +0100

Abstract (Source: Hematological Oncology)

Burkitt lymphoma versus diffuse large B‐cell lymphoma: a practical approach

Hematological Oncology — Mon, 31 May 2010 23:00:00 +0100

Abstract (Source: Hematological Oncology)

Clinical characteristics and outcome of isolated extracerebral relapses of primary central nervous system lymphoma: a case series

Hematological Oncology — Sun, 23 May 2010 23:00:00 +0100

In conclusion, isolated systemic relapses exist but are infrequent. Early EC relapse suggests the presence of systemic disease undetectable by conventional evaluation at initial diagnosis. Patient follow-up must be prolonged because systemic relapse can occur as late as 10 years after initial diagnosis. Whether EC relapses of PCNSL have a better prognosis than CNS relapses needs to be assessed in a larger cohort. Copyright © 2010 John Wiley & Sons, Ltd. (Source: Hematological Oncology)

Continuous sequential infusion of fludarabine and cytarabine for elderly patients with acute myeloid leukaemia secondary to a previously diagnosed myelodysplastic syndrome

Hematological Oncology — Mon, 10 May 2010 23:00:00 +0100

Acute myeloid leukaemia (AML) secondary to myelodysplastic syndrome (MDS) is characterized by poor prognosis, namely in older patients. The combination of fludarabine (F) with cytarabine (ARA-C) ± G-CSF was proven as effective in patients with poor risk AML. The efficacy and toxicity of a regimen including F + ARA-C as sequential continuous infusion (CI-FLA) in 64 untreated patients aged >60 years, in which AML arose after a previous MDS, was investigated. Median age was 67 years (61-81). In patients achieving CR, an additional course, followed by G-CSF to mobilize CD34+ cells and subsequent autologous stem cell transplantation (ASCT) were programmed. Overall, 43 patients (67%) achieved complete remission (CR). There were 10 induction deaths (16%), while 11 patients (17%) were refractory ...

Endothelial cells (EC) and endothelial precursor cells (EPC) kinetics in hematological patients undergoing chemotherapy or autologous stem cell transplantation (ASCT)

Hematological Oncology — Wed, 28 Apr 2010 23:00:00 +0100

In conclusion, we have found that hematological patients have higher number of EC and lower numbers of CFU-En than healthy controls and that these parameters do not return to normal after short-term follow-up. Furthermore, our observations support emerging data that CFU-En represent cell population different from flowcytometrically defined EC and endothelial precursors and that their development requires cooperation of monocytes and CD4+ lymphocytes. However, cells forming CFU-En express endothelial surface markers and can contribute to proper endothelial function by NO production. Copyright © 2010 John Wiley & Sons, Ltd. (Source: Hematological Oncology)

A non-functioning vitamin D receptor predisposes to leukaemoid reactions in mice

Hematological Oncology — Sat, 20 Mar 2010 00:00:00 +0100

The vitamin D hormone 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], the biologically active form of vitamin D, is not only essential for mineral metabolism but may have important functions beyond calcium homoeostasis. By gene targeting, we have recently generated mice expressing a functionally inactive mutant vitamin D receptor (VDR). After a change in environmental conditions from specific pathogen free (SPF) conditions to a modified barrier system, a high percentage of aged mutant, but not wild-type, mice developed a haematological disorder characterized by splenomegaly, granulocytosis, thrombocytosis and dysplastic changes with displacement of erythropoiesis in bone marrow during the following months. All cases were associated with very high serum levels of the acute phase reaction protein se...

Multicentre phase II study of CyclOBEAP plus rituximab in patients with diffuse large B-cell lymphoma

Hematological Oncology — Wed, 17 Mar 2010 00:00:00 +0100

The R-CHOP regimen has been found to improve the outcome of diffuse large B-cell lymphoma (DLBCL). However, it does not provide a satisfactory treatment outcome in the high-risk group. We previously administered the CyclOBEAP regimen to patients with DLBCL, and reported its safety and efficacy. The R-CyclOBEAP regimen was administered over a total period of 12 weeks, and rituximab 375 mg/m2 was given every 2 weeks. There were 101 eligible patients. CR was achieved in 96 patients (95%). The 5-year overall survival (OS) rate was 85% and progression-free survival (PFS) rate was 76%. When the patients were divided according to the IPI, the 5-year OS and PFS rates did not significantly differ among the risk groups. The 5-year PFS of the germinal centre B-cell group was 80% and that of the non-G...

Fertility preservation after chemotherapy for Hodgkin lymphoma

Hematological Oncology — Tue, 16 Mar 2010 00:00:00 +0100

Treatment for Hodgkin lymphoma can negatively affect fertility. This review summarizes data on fertility after chemotherapy in adult patients. Alkylating chemotherapy, especially if containing procarbazine and/or cyclophosphamide, is most harmful to gonadal functioning. Alkylating regimens cause prolonged azoospermia in 90-100% of men and ovarian failure in 5-25% of women under the age of 30. Non-alkylating chemotherapy, like ABVD, is much less harmful: one-third of male patients develop transient azoospermia, and almost no female patients experience ovarian failure. Age is an important factor for women: females over 30 years have a much higher risk of acute ovarian failure. However, with long-term follow-up the cumulative risk of menopause before the age of 40 becomes the same irrespectiv...

Telomeres and telomerase in normal and malignant B-cells

Hematological Oncology — Mon, 08 Mar 2010 00:00:00 +0100

The telomeric checkpoint is emerging as a critical sensor of cellular damage, playing a major role in human aging and cancer development. In the meantime, telomere biology is rapidly evolving from a basic discipline to a translational branch, capable of providing major hints for biomarker development, risk assessment and targeted treatment of cancer. These advances have a number of implications in the biology of lymphoid tumours. Moreover, there is considerable interest in the potential role of telomeric dysfunction in the wide array of immunological abnormalities, grouped under the definition of 'immunosenescence'. This review will summarize the impact of recent advances in telomere biology on the physiology and pathology of the B lymphocyte, with special interest in immunosenescence and ...

Vav-1 expression correlates with NF[kappa]B activation and CD40-mediated cell death in diffuse large B-cell lymphoma cell lines

Hematological Oncology — Sat, 13 Feb 2010 00:00:00 +0100

Diffuse large B-cell lymphoma (DLBCL) is an aggressive malignancy with a variable response to therapy. We have previously shown that DLBCL cell lines differ in their susceptibility to CD40-mediated cell death, and that resistance to CD40-targeted antibodies correlated with increased expression of markers of immature B-cell and absence of Vav-1 mRNA. We used gene expression profiling to investigate the mechanism of CD40 resistance in these cell lines, and found that resistance correlated with lack of Vav-1 and inability to activate NF[kappa]B upon CD40 ligation. Analysis of tissue microarrays of 213 DLBCL cases revealed that Vav-1 expression correlated with a higher proliferative index and the presence of the post-germinal centre marker Irf-4. Our results suggest that Vav-1 expression may b...

Abnormal protein bands in patients with multiple myeloma after haematopoietic stem cell transplantation: does it have a prognostic significance?

Hematological Oncology — Fri, 12 Feb 2010 00:00:00 +0100

Abnormal protein bands (APB) unrelated to the original monoclonal protein occasionally appear in serum immunofixation samples from patients with multiple myeloma (MM) following haematopoietic stem cell transplantation (HCT). To investigate the significance of APB, medical records and serum immunofixation patterns of 53 MM patients, who had undergone HCT (49 autologous and 4 allogeneic) at the stem cell transplantation unit of Gazi University Faculty of Medicine, were reviewed. Patients were staged according to Durie-Salmon and International staging systems (ISS) and disease response was determined according to European Bone Marrow Transplantation (EBMT) criteria. Fourteen (26.4%) of the 53 patients developed APBs after HCT. The median time for the appearance and duration of APB was 3 (rang...

Impact of Epstein-Barr virus in the clinical evolution of patients with classical Hodgkin's lymphoma in Brazil

Hematological Oncology — Wed, 03 Feb 2010 00:00:00 +0100

Classical Hodgkin's Lymphoma (cHL) has been frequently associated with Epstein-Barr virus (EBV), which can be found in a latent pattern in Reed-Sternberg (RS) cells. However, the impact of the presence of EBV in RS cells and its prognosis are still controversial. We analysed the presence of EBV in RS cells and its influence in the clinical evolution of patients with cHL treated in two public hospitals in the city of São Paulo, Brazil.We selected 97 patients with cHL from 1994 to 2004. Patients were only included in this study if they had (1) >18 years, (2) negative HIV serology, (3) undergone similar chemotherapy protocols, (4) paraffin blocks available with enough material for systematic review and histological reclassification and for detection of EBV in RS cells by in situ hybridizatio...

Genetic and epigenetic changes linked to Chlamydophila psittaci-associated ocular adnexal lymphomas

Hematological Oncology — Tue, 02 Feb 2010 00:00:00 +0100

No Abstract. (Source: Hematological Oncology)

Genomic profiling of enzastaurin‐treated B cell lymphoma RL cells

Hematological Oncology — Fri, 01 Jan 2010 00:00:00 +0100

(Source: Hematological Oncology)

The duration of the use of imatinib mesylate is only weakly related to elevated BNP levels in chronic myeloid leukaemia patients

Hematological Oncology — Fri, 01 Jan 2010 00:00:00 +0100

Abstract (Source: Hematological Oncology)

Expression of glucocorticoid receptor spliced variants in lymphoma cell lines

Hematological Oncology — Fri, 01 Jan 2010 00:00:00 +0100

(Source: Hematological Oncology)

Impact of Epstein–Barr virus in the clinical evolution of patients with classical Hodgkin's lymphoma in Brazil

Hematological Oncology — Fri, 01 Jan 2010 00:00:00 +0100

(Source: Hematological Oncology)

Vav‐1 expression correlates with NFκB activation and CD40‐mediated cell death in diffuse large B‐cell lymphoma cell lines

Hematological Oncology — Fri, 01 Jan 2010 00:00:00 +0100

(Source: Hematological Oncology)

Telomeres and telomerase in normal and malignant B‐cells

Hematological Oncology — Fri, 01 Jan 2010 00:00:00 +0100

(Source: Hematological Oncology)

A non‐functioning vitamin D receptor predisposes to leukaemoid reactions in mice

Hematological Oncology — Fri, 01 Jan 2010 00:00:00 +0100

(Source: Hematological Oncology)

Epidemiology and management of lymphoma in low‐income countries

Hematological Oncology — Fri, 01 Jan 2010 00:00:00 +0100

(Source: Hematological Oncology)

Immune reconstitution of B‐cell lymphoma patients receiving CHOP‐based chemotherapy containing rituximab

Hematological Oncology — Fri, 01 Jan 2010 00:00:00 +0100

(Source: Hematological Oncology)

Reduced‐intensity conditioning allogeneic transplant in heavily pre‐treated chronic lymphocytic leukaemia patients: a single centre experience

Hematological Oncology — Fri, 01 Jan 2010 00:00:00 +0100

(Source: Hematological Oncology)

LACE‐conditioned autologous stem cell transplantation for relapsed or refractory diffuse large B‐cell lymphoma: treatment outcome and risk factor analysis from a single centre

Hematological Oncology — Fri, 01 Jan 2010 00:00:00 +0100

(Source: Hematological Oncology)

Diffuse large B‐cell lymphoma with concordant bone marrow involvement has peculiar genomic profile and poor clinical outcome

Hematological Oncology — Fri, 01 Jan 2010 00:00:00 +0100

(Source: Hematological Oncology)

The prevalence and clinical significance of 18F–2‐fluoro‐2‐deoxy‐D‐glucose (FDG) uptake in the thyroid gland on PET or PET‐CT in patients with lymphoma

Hematological Oncology — Fri, 01 Jan 2010 00:00:00 +0100

(Source: Hematological Oncology)

Lack of allelic exclusion by secondary rearrangements of tumour B‐cell receptor light chains in hairy cell leukaemia

Hematological Oncology — Fri, 01 Jan 2010 00:00:00 +0100

(Source: Hematological Oncology)

Relevance of a scoring system including CD11c expression in the identification of splenic diffuse red pulp small B‐cell lymphoma (SRPL)

Hematological Oncology — Fri, 01 Jan 2010 00:00:00 +0100

(Source: Hematological Oncology)

Genomic profiling of Richter's syndrome: recurrent lesions and differences with de novo diffuse large B-cell lymphomas

Hematological Oncology — Mon, 14 Dec 2009 00:00:00 +0100

In conclusion, the genomic profile of RS seems to differ from what observed in de novo DLBCL and in other transformed DLBCL. Genomic lesions occurring in RS are heterogeneous suggesting the existence of different RS subsets, possibly due to different transforming mechanisms. A deregulation of MYC pathway might represent one of the main transformation events in the pathogenesis of a subset of RS clonally related to the previous CLL. Copyright © 2009 John Wiley & Sons, Ltd. (Source: Hematological Oncology)

The clinical relevance of Wilms Tumour 1 (WT1) gene mutations in acute leukaemia

Hematological Oncology — Wed, 09 Dec 2009 00:00:00 +0100

Recurrent genetic aberrations are important predictors of outcome in acute myeloid leukaemia (AML). Numerous novel molecular abnormalities have been identified and investigated in recent years adding to the risk stratification and prognostication of conventional karyotyping. Mutations in the Wilms Tumour 1 (WT1) gene were first described more than a decade ago but their clinical significance has only recently been evaluated. WT1 mutations occur in approximately 10% of adult AML patients at diagnosis and are most frequent in the cytogenetically normal (CN) AML subgroup. These mutations appear to confer a negative prognostic outcome by increasing the risk of relapse and death. Mutation frequency is higher in pediatric patients and also appears to confer a negative impact on relapse and survi...

Outcomes for lymphoid malignancies in the Nurses' Health Study (NHS) as compared to the Surveillance, Epidemiology and End Results (SEER) Program

Hematological Oncology — Wed, 28 Oct 2009 00:00:00 +0100

Vital statistics for the lymphoid malignancies obtained from the Surveillance, Epidemiology and End Results (SEER) Program have seldom been directly compared to data from alternative national databases. While SEER is recognized as the standard, some lymphoid malignancies - especially the chronic ones - may be underreported. We compared the incidence, all-cause and cause-specific mortality for Hodgkin's lymphoma (HL), non-Hodgkin's lymphoma (NHL), multiple myeloma (MM) and chronic lymphocytic leukaemia (CLL) in SEER to that in the Nurses' Health Study (NHS), a national cohort study of 121 700 female registered nurses, matching for age and race. In over 2.5 million person-years, the incidence of HL was the same as in SEER (SIR = 1.01 [0.75, 1.26]), while the incidence of NHL, CLL and MM were...

Silibinin can induce differentiation as well as enhance vitamin D3-induced differentiation of human AML cells ex vivo and regulates the levels of differentiation-related transcription factors

Hematological Oncology — Wed, 28 Oct 2009 00:00:00 +0100

Induction of terminal differentiation is a conceptually attractive approach for the therapy of neoplastic diseases. Although vitamin D derivatives (deltanoids) can induce differentiation of AML cells in vitro, so far deltanoids have not been successfully brought to the clinic, due to the likelihood of life-threatening hypercalcemia. Here, we incubated freshly obtained blood cells from patients with AML with a plant antioxidant (PAOx), silibinin (SIL), alone or together with a deltanoid. Twenty patients with AML (all subtypes except M3) were available for this study, and in 14 (70%), SIL (60 µM) either induced differentiation ex vivo, or enhanced differentiation induced by deltanoids, or both. Interestingly, SIL acting alone induced differentiation only in cases in which chromosome aberrat...

Burkitt lymphoma versus diffuse large B-cell lymphoma: a practical approach

Hematological Oncology — Tue, 20 Oct 2009 23:00:00 +0100

Burkitt Lymphoma (BL) is listed in the World Health Organization (WHO) classification of lymphoid tumours as an 'aggressive B-cell non-Hodgkin's lymphoma', characterized by a high degree of proliferation of the malignant cells and deregulation of the c-MYC gene. The main diagnostic challenge in BL is to distinguish it from diffuse large B-cell lymphoma (DLBCL). While in children BL and DLBCL types probably do not differ clinically, and the differential diagnosis between BL and DLBCL may theoretically appear clear-cut, in adults daily practice shows the existence of cases that have morphological features, immunophenotypic and cytogenetics intermediate between DLBCL and BL, and cannot be classified with certainty in these categories. Distinguishing between BL and DLBCL is critical, as the tw...

Clofarabine in the treatment of poor risk acute myeloid leukaemia

Hematological Oncology — Thu, 17 Sep 2009 23:00:00 +0100

In conclusion, clofarabine (alone or in combination) is active in poor risk AML with an acceptable safety profile and should be considered a potential option in poor risk AML patients. Copyright © 2009 John Wiley & Sons, Ltd. (Source: Hematological Oncology)

Dynamic change of T315I BCR-ABL kinase domain mutation in Korean chronic myeloid leukaemia patients during treatment with Abl tyrosine kinase inhibitors

Hematological Oncology — Thu, 17 Sep 2009 23:00:00 +0100

We analysed the dynamic change of imatinib-resistant mutations in BCR-ABL kinase domain focusing on T315I mutation during dasatinib or nilotinib therapy. Fifty-five imatinib-resistant chronic myeloid leukaemia patients (32 patients with imatinib-resistant mutations and 23 patients without mutation) in different disease phases were treated with dasatinib (median 17.3 months) or nilotinib (median 6.8 months). Among the 32 patients with baseline mutation, mutations including M244V, G250E, E255K, M351T, H396R, S417Y, E450K and E459K disappeared in 8 patients and new mutations were detected in 9 patients, all of which were T315I. Among the 23 patients without baseline mutation, 4 patients showed newly developed mutations including T315I, T315I + E459K, M244V and F359V. The T315I was the most fr...

Severe pulmonary complications after bortezomib treatment in multiple myeloma

Hematological Oncology — Wed, 02 Sep 2009 23:00:00 +0100

No Abstract. (Source: Hematological Oncology)

CT-guided percutaneous lung biopsies in patients with haematologic malignancies and undiagnosed pulmonary lesions

Hematological Oncology — Wed, 02 Sep 2009 23:00:00 +0100

We searched the electronic patient database at The University of Texas M. D. Anderson Cancer Center for patients who underwent computed tomography (CT)-guided needle biopsy between January 2001 and December 2005. Inclusion criteria were a known history of haematologic malignancy and a newly detected, undiagnosed pulmonary lesion on chest CT that required tissue sampling for diagnosis; 213 met these criteria. We analysed the biopsy results for diagnostic yield, factors affecting diagnostic yield and effect on treatment. Of 213 procedures, 191 (89.7%) yielded sufficient material for pathologic analysis; 130 (60%) yielded specific diagnoses, while 61 (28.6%) yielded nonspecific benign diagnoses. Lesions larger than 1 cm, cavitary lesions and lung masses were more likely to yield a specific di...

Geographic variation and environmental conditions as cofactors in Chlamydia psittaci association with ocular adnexal lymphomas: a comparison between Italian and African samples

Hematological Oncology — Wed, 02 Sep 2009 23:00:00 +0100

This study was designed to investigate the possible association of Chlamydia psittaci in cases retrieved from Kenya, compared to cases from Italy. Our results showed that there was a marked variation between the two geographical areas in terms of association with C. psittaci, as 17% (5/30) of the samples from Italy were positive for C. psittaci, whereas no association with this pathogen was observed in any of the African samples (0/9), suggesting that other cofactors may determine the OAL occurrence in those areas. OAL cases are often characterized by down-regulation of p16/INK4a expression and promoter hypermethylation of the p16/INK4a gene. Our results showed a partial methylation of p16/INK4a promoter in C. psittaci-negative cases, whereas no hypermethylation of this gene was found in C...

Cytogenetic and molecular responses in chronic phase chronic myeloid leukaemia patients receiving low dose of imatinib for intolerance to standard dose

Hematological Oncology — Wed, 02 Sep 2009 23:00:00 +0100

We report the outcome of 45 CML patients in early (17) and late (28) chronic phase (CP) in whom, within a series of 250 patients treated with imatinib, reduced the dose of the drug after experiencing adverse events. Median time interval between the start of therapy and dose reduction was 58 days, whereas median administered dose was 300 mg/day. At 6 months from reduction, major cytogenetic responses (MCRs) were observed in 67% of patients, with 58% being complete cytogenetic remission (CCR), and complete molecular response (CMR) were obtained in 18% of patients. At 12 months, all patients who had obtained MCR reached CCR: this was significantly higher in low risk patients (87%) versus non-low risk patients (66 and 46%), and in early phase (82%) versus late phase (53.5%). CMR and major mole...

Clinical characteristics of patients with chronic eosinophilic leukaemia (CEL) harbouring FIP1L1-PDGFRA fusion transcript - results of Polish multicentre study

Hematological Oncology — Wed, 02 Sep 2009 23:00:00 +0100

In conclusion, significant clinical symptoms are infrequent present and splenomegaly remains the most common organ involvement in patients with CEL expressing F/P fusion transcript. Our study confirmed the long-term remission on imatinib in this patient population. Copyright © 2009 John Wiley & Sons, Ltd. (Source: Hematological Oncology)

Burkitt lymphoma versus diffuse large B-cell lymphoma: a practical approach

Hematological Oncology — Mon, 10 Aug 2009 23:00:00 +0100

Burkitt Lymphoma (BL) is listed in the World Health Organization (WHO) classification of lymphoid tumours as an "aggressive B-cell non-Hodgkin's lymphoma", characterized by a high degree of proliferation of the malignant cells and deregulation of the c-MYC gene. The main diagnostic challenge in BL is to distinguish it from diffuse large B-cell lymphoma (DLBCL). While in children BL and DLBCL types probably do not differ clinically, and the differential diagnosis between BL and DLBCL may theoretically appear clear-cut, in adults daily practice shows the existence of cases that have morphological features, immunophenotypic and cytogenetics intermediate between DLBCL and BL, and cannot be classified with certainty in these categories. Distinguishing between BL and DLBCL is critical, as the tw...

Remission induction, consolidation and novel agents in development for adults with acute myeloid leukaemia

Hematological Oncology — Thu, 30 Jul 2009 23:00:00 +0100

Chemotherapy regimens used for remission induction in AML have not changed significantly over the last several decades. However the recognition of the prognostic value of cytogenetics and genomics has been a major advance which is helping clarify the most optimal post-remission consolidation strategy among various risk groups. We are not only beginning to realize the pitfalls of a 'one-fits-all' approach with intensive, cytarabine-based chemotherapy as the mainstay, but we are finally beginning to reap the rewards of decades of basic, translational, and clinical research. Developing individualized, 'targeted' therapy for each AML patient based on unique molecular features of disease remains a daunting goal yet one that we can now begin to envision. Hypothesis-based study designs - from pre...

The root of many evils: indolent large granular lymphocyte leukaemia and associated disorders

Hematological Oncology — Thu, 30 Jul 2009 23:00:00 +0100

Large granular lymphocytes (LGL) leukaemia can arise from either natural killer (NK) cells or cytotoxic T lymphocytes (CTL). The T-cell form of LGL leukaemia has significant overlap with other haematological disorders and autoimmune diseases. Here we provide an overview of LGL biology. We also focus discussion on the indolent LGL leukaemia related disorders and their causal relationships. We then discuss the potential relationships and distinctions between indolent LGL leukaemia and non-malignant clonal lymphocyte expansion that occur in otherwise healthy individuals, especially elder people. Copyright © 2009 John Wiley & Sons, Ltd. (Source: Hematological Oncology)

18F-FDG uptake and its clinical relevance in primary gastric lymphoma

Hematological Oncology — Fri, 10 Jul 2009 23:00:00 +0100

In conclusion, PET/CT scan can be used in staging patients with primary gastric lymphoma; however, the residual 18F-FDG uptake observed during follow-up should be interpreted cautiously and should be combined with endoscopy and multiple biopsies of the stomach. Copyright © 2009 John Wiley & Sons, Ltd. (Source: Hematological Oncology)

Experimental and clinical characteristics in myelodysplastic syndrome patients with or without HLA-DR15 allele

Hematological Oncology — Thu, 09 Jul 2009 23:00:00 +0100

We studied the effects of the presence of the HLA-DR15 allele on the experimental and clinical features of myelodysplastic syndrome (MDS) by assessing the clinical data of 136 patients with MDS. We observed that the frequency of HLA-DR15 expression in MDS patients (38.7%) was significantly higher than that in the healthy controls (p < 0.01). We noted the following observations with regard to disease progression: None of the 46 HLA-DR15 positive patients with international prognostic scoring system (IPSS) scores [le]1 developed acute myeloid leukaemia (AML) during the follow-up period, while six of the 63 DR15-negative patients with the same IPSS score developed AML within a shorter follow-up period (p = 0.039). Furthermore, the incidence of poor chromosomal abnormalities, the percentage of...

Two novel NPM1 mutations in a therapy-responder AML patient

Hematological Oncology — Thu, 09 Jul 2009 23:00:00 +0100

We describe a case of a therapy-responder acute myeloid leukaemia (AML) patient bearing two novel NPM1 mutations. Cells' transfection studies indicate that the presence of one of these mutations is associated to an abnormal nucleolar structure, suggesting that NPM1 may contribute to the control of nucleolar integrity. Copyright © 2009 John Wiley & Sons, Ltd. (Source: Hematological Oncology)

Nucleophosmin (NPM1) mutations in adult and childhood acute myeloid leukaemia: towards definition of a new leukaemia entity

Hematological Oncology — Tue, 30 Jun 2009 23:00:00 +0100

Nucleophosmin (NPM) is a ubiquitously expressed chaperone protein that shuttles rapidly between the nucleus and cytoplasm, but predominantly resides in the nucleolus. It plays key roles in ribosome biogenesis, centrosome duplication, genomic stability, cell cycle progression and apoptosis. Somatic mutations in exon 12 of the NPM gene (NPM1) are the most frequent genetic abnormality in adult acute myeloid leukaemia (AML), found in approximately 35% of all cases and up to 60% of patients with normal karyotype (NK) AML. In children, NPM1 mutations are far less frequent, occurring in 8-10% of all AML cases, and in approximately 25% of those with a NK. NPM1 mutations lead to aberrant localization of the NPM protein into the cytoplasm, thus the designation, NPMc+ AML. NPMc+ AML is seen predomina...

Telomeres and telomerase in chronic myeloid leukaemia: impact for pathogenesis, disease progression and targeted therapy

Hematological Oncology — Tue, 30 Jun 2009 23:00:00 +0100

Telomeres are specialized structures localized at the end of human chromosomes. Due to the end replication problem, each cell division results in a loss of telomeric repeats in normal somatic cells. In germ line and stem cells, the multicomponent enzyme telomerase maintains the length of telomere repeats. However, elevated telomerase activity has also been reported in the majority of solid tumours as well as in acute and chronic leukaemia. Chronic myeloid leukaemia (CML) serves as a model disease to study telomere biology in clonal myeloproliferative disorders. In CML, telomere shortening correlates with disease stage, duration of chronic phase (CP), prognosis measured by the Hasford risk score and the response to disease-modifying therapeutics such as the tyrosine kinase inhibitor Imatini...

How would I manage a sample submitted for flow cytometry analysis for suspicious chronic lymphocytic leukaemia

Hematological Oncology — Tue, 30 Jun 2009 23:00:00 +0100

Samples submitted for a suspect of chronic lymphocytic leukemia are the most frequently observed in flow cytometry laboratories. These cases require not only a precise and prompt diagnosis but also an evaluation on the possibility of performing additional prognostic tests. We will propose two sequential flow cytometry panels and a personal opinion on how to manage these samples for both diagnostic and prognostic assessment, taking into account the published guidelines and recommendations. Copyright © 2009 John Wiley & Sons, Ltd. (Source: Hematological Oncology)

New antimicrobial agents for the treatment of bacterial infections in cancer patients

Hematological Oncology — Tue, 30 Jun 2009 23:00:00 +0100

Patients with cancer develop serious bacterial infections often, especially during periods of severe and prolonged neutropenia. Antibiotic usage for the prevention and treatment of bacterial infections in these high-risk patients leads to selection pressures resulting in the emergence and spread of resistant organisms. Many organisms acquire several resistance mechanisms, making them multi-drug-resistant (MDR) (defined as resistance to three or more different classes of antibiotics). These infections are associated with increased morbidity, mortality and costs. The development of novel antimicrobial agents with activity against pathogens that have become resistant to currently available agents is one strategy for combating resistant organisms. Several novel agents have either recently been...

Improved survival in red blood cell transfusion dependent patients with primary myelofibrosis (PMF) receiving iron chelation therapy

Hematological Oncology — Wed, 24 Jun 2009 23:00:00 +0100

In conclusion, 61% of PMF patients developed RBC-TD which portended inferior OS; however patients receiving ICT had comparatively improved OS, suggesting a clinical benefit. Prospective studies of IOL and the impact of ICT in PMF are warranted. Copyright © 2009 John Wiley & Sons, Ltd. (Source: Hematological Oncology)

Continuous infusion idarubicin and intravenous busulphan as conditioning regimen to autologous stem cell transplantation for patients with acute myeloid leukaemia

Hematological Oncology — Sat, 30 May 2009 04:00:00 +0100

The current study aimed to evaluate the efficacy and toxicity of a combination of intravenous (iv) busulfan (Bu) and continuous infusion Idarubicin (IDA) as a conditioning regimen to autologous haematopoietic stem cell transplantation (ASCT) in patients with acute myeloid leukaemia (AML). The protocol included IDA at 20 mg/sqm daily as 3 days continuous infusion (from day -13 to -11) and intravenous BU at 3.2 mg/kg daily from day -5 to -2. Patients aged over 60 years received a reduced schedule (2 days IDA and 3 days BU at the same dose). Twenty-five patients with a median age of 51 years (28-72) were enrolled. All patients received peripheral blood stem cells (PBSC). The median interval between diagnosis and ASCT was 4 months. The median number of CD34+ cells infused was 5.9 × 10E6/kg. T...

The therapeutic effect of rituximab on CD5-positive and CD5-negative diffuse large B-cell lymphoma

Hematological Oncology — Fri, 17 Apr 2009 04:00:00 +0100

The prognosis of diffuse large B-cell lymphoma (DLBCL) has improved markedly in recent years of rituximab era. The prognosis of de novo CD5-positive DLBCL is reported to be poor, but the effect of rituximab on this type of lymphoma remains unclear. To investigate the effect of rituximab on CD5-positive DLBCL, we collected DLBCL patients and analysed prognostic factors. A total of 157 patients with DLBCL who were immunophenotyped with flow-cytometry (FCM) and treated with chemotherapy were subjected to analysis. Those treated with radiotherapy alone or with supportive therapy only were not included. Patients diagnosed in 2003 or later were treated with rituximab combined chemotherapy. There were 95 males and 62 females. Their age ranged from 20 to 91 years old, and the median was 65 years. ...

Mutations of NPM1 gene in de novo acute myeloid leukaemia: determination of incidence, distribution pattern and identification of two novel mutations in Indian population

Hematological Oncology — Mon, 13 Apr 2009 04:00:00 +0100

In conclusion, this study represents the first report of NPM1 mutation from Indian population and confirms that the incidence of NPM1 mutations varies considerably globally, with slightly lower incidence in Indian population compared to western countries. The current study also served to identify two novel NPM1 mutants that add new insights into the heterogeneity of genomic insertions at exon 12. More ongoing larger studies are warranted to elucidate the molecular pathogenesis of AML that arises in this part of the world. Furthermore, we believe that in light of its high prevalence worldwide, inclusion of NPM1 mutation detection assay in diagnostic evaluations of AML may improve the efficacy of routine genetic characterization and allow assignment of patients to better-defined risk categor...

The role of stem cell transplantation in the management of chronic lymphocytic leukaemia

Hematological Oncology — Wed, 08 Apr 2009 04:00:00 +0100

The majority of patients diagnosed with chronic lymphocytic leukaemia (CLL) will ultimately die of their disease. Stem cell transplantation (SCT) remains the only treatment modality capable of cure, but has traditionally been associated with very high morbidity and mortality. We review the results of myeloablative autologous and allogeneic SCT in CLL, discuss the evolution of the new non-myeloablative approaches, and make recommendations for when SCT should be considered in patients with CLL. Copyright © 2009 John Wiley & Sons, Ltd. (Source: Hematological Oncology)

Anaplastic large cell lymphoma: one or more entities among T-cell lymphoma?

Hematological Oncology — Wed, 08 Apr 2009 04:00:00 +0100

Anaplastic large cell lymphoma (ALCL) is a subtype of peripheral T-cell lymphoma (PTCL) first described in 1985 as a lymphoid malignancy characterized by marked cellular pleomorphism, propensity to grow cohesively, tendency to invade lymph node sinuses and diffuse expression of CD30 . The discovery of the t(2;5), involving the anaplastic lymphoma kinase (ALK) gene on chromosome 2 and the nucleophosmin (NPM) gene on chromosome 5 in the majority of systemic ALCL, has soon pointed out that ALCL is a clinically and biologically heterogeneous disease. While ALK-positive (ALK+) ALCL is usually characterized by onset in children and young adults and better prognosis, epidemiology, poor outcome and possibly genetic defects of ALK-negative (ALK-) ALCL suggest that this neoplasms should be considere...

KHSV- EBV- post-transplant effusion lymphoma with plasmablastic features: variant of primary effusion lymphoma?

Hematological Oncology — Tue, 07 Apr 2009 04:00:00 +0100

We report a unique KSHV- EBV- post-transplant effusion lymphoma associated with serum paraproteins, occurring in an HIV- individual, which had cytologic features and phenotype similar to PEL, and displayed a complex karyotype including isochromosome 12p and translocation t(8;22), resulting in rearrangement of c-MYC. Copyright © 2009 John Wiley & Sons, Ltd. (Source: Hematological Oncology)

Immunotherapy with cytokine induced killer cells in solid and hematopoietic tumours: a pilot clinical trial

Hematological Oncology — Tue, 17 Mar 2009 04:00:00 +0100

Conclusions: These preliminary data showed that adoptive immunotherapy with CIK cells is a safe therapy with some suggestion of efficacy that significantly enhances immune functions increasing absolute numbers of effector cells without side effects. If confirmed in larger scale studies, these promising results may have a favourable impact on conventional treatment strategy of malignancies. Copyright © 2009 John Wiley & Sons, Ltd. (Source: Hematological Oncology)

Radiological findings of early invasive pulmonary aspergillosis in immune-compromised patients

Hematological Oncology — Tue, 17 Mar 2009 04:00:00 +0100

This study describes the radiological features of early stages of IPA. Chest computerized tomography (CT) films of 22 consecutive immune-compromised patients with IPA diagnosed with the aid of ASP PCR testing from BAL fluid were characterized and compared to that of 18 similar patients diagnosed with traditional bacteriological methods and to data from the literature. It was found that patients diagnosed with the aid of ASP PCR testing tended to have focal disease as manifested by more 11-30 mm nodules with halo (68% vs. 33%, p = 0.04), more focal ground glass (single area 32% vs. 6%, p = 0.05, patchy 32% vs. 0%, p = 0.01) and less diffuse ground glass (0% vs. 22%, p = 0.03), less cavitations (5% vs. 28%, p = 0.05) and less consolidations (segmental 14% vs. 50%, p = 0.02 and diffuse 14% vs...

Comorbidities and FLT3-ITD abnormalities as independent prognostic indicators of survival in Elderly acute myeloid leukaemia patients

Hematological Oncology — Wed, 11 Mar 2009 04:00:00 +0100

Elderly acute myeloid leukaemia (AML) patients have a dismal prognosis due to biological features of disease in itself and to presence of comorbidities. Aim of this study was to evaluate the prognostic impact of comorbidity prognostic score systems applied in our population of patients. as well as other clinical-biological features. We retrospectively considered the outcome of 120 patients aged >65 years diagnosed as having AML between January 2001 and December 2005. Comorbidities were evaluated by using Charlson comorbidity index (CCI), Hematopoietic cell transplantation comorbidity index (HCTCI) and a score proposed by Dombret et al. in 2007. Median patient age was 67 years. Forty-six patients were treated with intensive chemotherapy and 23 reached a complete remission. Seventy-four pati...

MPL W515L/K mutations in 343 Chinese adults with JAK2V617F mutation-negative chronic myeloproliferative disorders detected by a newly developed RQ-PCR based on TaqMan MGB probes

Hematological Oncology — Sun, 08 Mar 2009 05:00:00 +0100

Acquired mutations in the juxtamembrane region of MPL (W515L or W515K), the receptor for thrombopoietin, have been reported in patients with primary essential thrombocythemia (ET) or primary myelofibrosis (PMF). The mutations were detected by the newly developed real-time quantitative PCR (RQ-PCR) with TaqMan MGB probes and followed by the sequencing analysis. DNA samples were from 343 Chinese adults with JAK2V617F mutation-negative chronic myeloproliferative disorders (cMPDs). Reference curves were obtained using cloned fragments of MPL containing either the wild-type or MPL W515L or MPL W515K mutated sequence; the predicted sensitivity level was at least 0.5%(0.1-0.5%) for MPL W515L and 0.5%(0.2-0.5%) for MPL W515K mutant allele in a wild-type background. The detection rates of MPL W515 ...

Analysis of Bcr-Abl kinase domain mutations in Korean chronic myeloid leukaemia patients: poor clinical outcome of P-loop and T315I mutation is disease phase dependent

Hematological Oncology — Sun, 08 Mar 2009 05:00:00 +0100

Despite durable responses to imatinib in chronic myeloid leukaemia (CML), mutations in Bcr-Abl kinase domain (KD) are known to induce imatinib resistance and cause poor clinical outcome. We characterized Bcr-Abl KD mutations in 137 Korean CML patients with imatinib resistance (n = 111) or intolerance (n = 26) using allele specific oligonucleotide polymerase chain reaction (PCR) and direct sequencing. Seventy (51%) patients harboured 81 mutations of 20 different types with increasing prevalence in advanced phase. Nine (13%) patients had multiple mutations. No mutation was found in intolerant patients. T315I was the most common mutation and P-loop was the hottest spot in Bcr-Abl KD. Patients harbouring P-loop mutation, T315I, or multiple mutations showed poor overall survival and progression...

A multicentre phase II trial of gemcitabine for the treatment of patients with newly diagnosed, relapsed or chemotherapy resistant mantle cell lymphoma: SAKK 36/03

Hematological Oncology — Sun, 08 Mar 2009 05:00:00 +0100

Mantle cell lymphoma (MCL) has a poor prognosis with often short and incomplete remissions. We aimed to test the efficacy and tolerability of gemcitabine in treating MCL. Gemcitabine was given in doses of 1000 mg/m2 as a 30 min infusion on days 1 and 8 of each 3 week cycle for a maximum of nine cycles. Eighteen patients with a median age of 70 years were recruited. MCL was newly diagnosed in half of patients and relapsed in the remainder. Fifteen patients had Ann Arbor stage IV. The best-recorded responses were 1 CR (complete remission), 4 PRs (partial responses), 8 SDs (stable diseases) and 4 PDs (diseases progression). The response rate (RR) (CR + PR) was 5 (28%; 95% confidence interval: 7.1, 48.5). The patient achieving a CR had stage IV disease. Most haematological adverse events occur...

Involved field radiotherapy for limited stage Hodgkin lymphoma: balancing treatment efficacy against long-term toxicities

Hematological Oncology — Sun, 08 Mar 2009 05:00:00 +0100

Limited stage Hodgkin lymphoma (HL) refers to patients with stage IA or IIA disease in the absence of any bulky mass or unfavourable prognostic factors. In this group, the long-term disease control with treatment can be expected in more than 90%, and management has now been directed to make strategies to reduce late morbidities related to therapy. With the advent of very effective chemotherapy, the role of radiation therapy has evolved from a first line single modality treatment, to an adjuvant therapy following brief cycles of chemotherapy. Optimal radiation volume and dose parameters have been refined in the combined modality setting. Furthermore, with the progress in diagnostic functional imaging and advances in radiotherapy, it is possible to accurately deliver low to moderate doses of...