Allo-HSCT in transplant-naïve patients with Hodgkin lymphoma: a single-arm, multicenter study.

We evaluated the role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in transplant-naïve patients with relapsed/refractory Hodgkin lymphoma (HL) who failed to attain metabolic complete response (mCR) to 1 to 2 lines of salvage chemotherapyThose with residual but nonprogressive disease assessed by positron emission tomography/computed tomography scanning were eligible. An additional 1 to 2 cycles of salvage therapy were permissible in those with progressive disease or when required to bridge to allo-HSCT, with additional imaging at baseline before transplantation. Conditioning consisted of carmustine, etoposide, cytarabine, melphalan, and alemtuzumab.

Recurrent activating STAT5B N642H mutation in myeloid neoplasms with eosinophilia.

Determining the underlying cause of persistent eosinophilia is important for effective clinical management but remains a diagnostic challenge in many cases. We identified STAT5B N642H, an established oncogenic mutation, in 27/1715 (1.6%) cases referred for investigation of eosinophilia.

Addition of the mammalian target of rapamycin inhibitor, everolimus, to consolidation therapy in acute myeloid leukemia: experience from the UK NCRI AML17 trial.

As part of the UK NCRI AML17 trial, adult patients with acute myeloid leukemia in remission could be randomized to receive the mammalian target of rapamycin inhibitor everolimus, sequentially with post-induction chemotherapy. Three hundred and thirty-nine patients were randomised (2:1) to receive everolimus or not for a maximum of 84 days between chemotherapy courses. The primary endpoint was relapse-free survival.

Extracorporeal photopheresis as second-line treatment for acute graft-versus-host disease: impact on six-month freedom from treatment failure.

Second-line therapy for corticosteroid-refractory or -dependent acute graft-versus-host disease remains ill-defined, due to limited efficacy of drugs and evolving clinical trial endpoints. Six-month freedom from treatment failure has been proposed as a novel clinical trial endpoint and is defined by the absence of death, malignancy relapse/progression, or addition of a next line of systemic immunosuppressive therapy within 6 months of intervention and prior to diagnosis of chronic graft-versus-host disease. We analyzed the 6-month freedom from treatment failure endpoint in 128 patients enrolled from three centers who were treated with extracorporeal photopheresis as second-line therapy for acute graft-versus-host disease.

Extracorporeal photopheresis versus anticytokine therapy as a second-line treatment for steroid-refractory acute GVHD: a multicenter comparative analysis.

The optimal therapy for steroid-refractory (SR) acute graft-versus-host disease (aGVHD) is undefined. We studied patients with SR aGVHD, comparing extracorporeal photopheresis (ECP; n = 57) and anticytokine therapy (n = 41). In multivariate analyses, ECP, adjusted for steroid dose (odds ratio, 3.

The acute impact of a hematopoietic allograft on lung function and inflammation: a prospective observational study.

Background: No studies have investigated the immediate impact of receiving an allogeneic hematopoietic stem cell transplant (HSCT) on pulmonary inflammation or lung function.

Methods: Using a prospective study design, we quantified the changes in these outcome measures in eligible adult individuals in the first six months after receiving an allogeneic hematopoietic stem cell transplant.

Results: Between January 2007 and December 2008, 72 patients were eligible to participate in the cohort, and of these 68 (94%) were included in the study.

Bone marrow transplantation in AML, and socioeconomic class: a UK population-based cohort study.

Background: We have previously shown that in the UK mortality in people with Acute Myeloid Leukaemia (AML) was nearly 50% greater among the most socio-economically deprived. The aim of this study was to determine whether AML patients from lower socioeconomic classes had a lower chance of receiving a bone marrow transplant.

Methods: Using Hospital Episode Statistics (HES) data, we identified all incident cases of AML admitted to UK hospitals between 1998 and 2007.

European development of clofarabine as treatment for older patients with acute myeloid leukemia considered unsuitable for intensive chemotherapy.

Purpose: Treatment options for older patients with acute myeloid leukemia (AML) who are not considered suitable for intensive chemotherapy are limited. We assessed the second-generation purine nucleoside analog, clofarabine, in two similar phase II studies in this group of patients.

Patients And Methods: Two consecutive studies, UWCM-001 and BIOV-121, recruited untreated older patients with AML to receive up to four or six 5-day courses of clofarabine.

The incidence of and mortality from leukaemias in the UK: a general population-based study.

Background: The acute and chronic leukaemias constitute about 2.5% of all newly diagnosed malignancies and kill over 4000 people/year in the UK, yet there is little accurate up-to-date data on how the incidence of and mortality from leukaemias vary with socio-economic status in the UK. We aimed to quantify the incidence of and mortality from leukaemias in the UK and their variation with gender, age, year of diagnosis as well as socio-economic status.

Outcome of BEAM-autologous and BEAM-alemtuzumab allogeneic transplantation in relapsed advanced stage follicular lymphoma.

The role of haematopoietic stem cell transplantation (HSCT) in relapsed follicular lymphoma remains controversial. This study analysed 126 patients with relapsed, advanced stage follicular lymphoma who received BEAM (BCNU [carmustine], cytarabine, etoposide, melphalan)-alemtuzumab allogeneic HSCT (BEAM-allo) (n = 44) or BEAM-autologous HSCT (BEAM-auto) (n = 82). The BEAM-allo group had a younger median age (48 years vs.

Long-term outcome of unrelated donor transplantation for AML using myeloablative conditioning incorporating pretransplant Alemtuzumab.

The outcome of 55 patients who underwent matched unrelated donor (MUD) transplantation for acute myelogenous leukemia (AML) following a conditioning regimen of cyclophosphamide and total-body irradiation (TBI) with the addition of Alemtuzumab 10 mg/kg/day on days -5 to -1 is described. All patients received graft-versus-host disease (GVHD) prophylaxis with cyclosporine as well as 3 doses of posttransplant methotrexate. Forty-one patients were transplanted in complete remission (CR) (20 in CR1, 20 in CR2, and 1 in CR3), and 14 were not in remission at the time of transplantation as they were refractory to chemotherapy either at induction or at relapse.

The impact of chimerism patterns and predonor leukocyte infusion lymphopenia on survival following T cell-depleted reduced intensity conditioned transplants.

Donor leukocyte infusions (DLI) are frequently required following reduced intensity conditioned (RIC) allografts to convert mixed chimerism (MC) to full donor chimerism (FDC). The rationale is to break tolerance and maximize the graft-versus-leukemia responses. We analyzed the impact of chimerism in 125 recipients of RIC (Alemtuzumab containing) transplants.

The impact of donor factors on primary non-engraftment in recipients of reduced intensity conditioned transplants from unrelated donors.

Background And Objectives: Primary graft failure is a serious complication following hematopoietic cell transplants, particularly when using unrelated donors. We analyzed factors affecting primary graft failure in recipients of hematopoietic cell transplants from unrelated donors, which were performed using reduced intensity conditioning.

Design And Methods: This was a retrospective analysis of 144 patients whose transplants took place between March 1998 and October 2004.

Flow cytometric measurement of functional and phenotypic P-glycoprotein.

The measurement of functional and phenotypic P-glycoprotein by flow cytometry is suitable for cells in suspension, and is particularly appropriate for blood and bone marrow cells. We describe a functional assay for P-glycoprotein using rhodamine 123, an assay for daunorubicin accumulation, and an assay to measure P-glycoprotein levels using the MRK16 antibody. Our protocols include the use of an anti-CD45 antibody for the identification of leukemic blasts.

Polymorphisms in genes involved in homologous recombination repair interact to increase the risk of developing acute myeloid leukemia.

Purpose: Double-strand break repair via homologous recombination is essential in maintaining genetic integrity. RAD51 and XRCC3 are involved in the repair of DNA by this pathway, and polymorphisms have been identified in both the RAD51 (RAD51-G135C) and XRCC3 (XRCC3-Thr241Met) genes. The object of this study was to examine whether these polymorphisms may modulate susceptibility to the development of acute myeloid leukemia (AML), a disease that is characterized by genetic instability.

BAT-25 and BAT-26, two mononucleotide microsatellites, are not sensitive markers of microsatellite instability in acute myeloid leukaemia.

BAT-25 and BAT-26 are mononucleotide microsatellites with quasi-monomorphic allele length distribution in healthy controls but unstable, shortened alleles in solid organ tumours with a mutator phenotype (RER+). Both markers are highly sensitive and specific for RER+ colorectal cancer. This study evaluated three mononucleotide microsatellites, BAT-25, BAT-26 and BAT-40 (a polymorphic mononucleotide microsatellite) in RER+ acute myeloid leukaemia (AML).

The genotype distribution of the XRCC1 gene indicates a role for base excision repair in the development of therapy-related acute myeloblastic leukemia.

Polymorphisms in several DNA repair genes have been described. These polymorphisms may affect DNA repair capacity and modulate cancer susceptibility by means of gene-environment interactions. We investigated DNA repair capacity and its association with acute myeloblastic leukemia (AML).