Diane Coso

The role of reduced intensity conditioning allogeneic stem cell transplantation in patients with acute myeloid leukemia: a donor vs no donor comparison

Using a genetic randomization through a ‘donor’ vs ‘no donor’ comparison, the aim of this analysis was to assess the real benefit of reduced intensity conditioning allogeneic stem cell transplantation (RIC-allo-SCT) among 95 adult high-risk acute myeloid leukemia (AML) patients. In an ‘intention-to-treat’ analysis, leukemia-free survival (LFS) was significantly higher in the ‘donor’ group as compared to the ‘no donor’ group (P=0.01; 54 vs 30% at 4 years). The latter held true when restricting the analysis to the 25 patients who could actually receive the RIC-allo-SCT (P=0.001). Overall transplant-related mortality in the ‘transplant’ group was 12%, with overall survival (OS) being significantly higher in the ‘transplant’ group as compared to the ‘no transplant’ group (P=0.01). Also, in the ‘intention-to-treat’ analysis, OS was significantly higher in the ‘donor’ group as compared to the ‘no donor’ group (P=0.04). In the multivariate analysis, actual performance of RIC-allo-SCT (P=0.001; RR=4.0; 95% CI, 1.7–9.6) was the strongest factor significantly predictive of an improved LFS. We conclude that if a matched related donor is identified, RIC-allo-SCT should be proposed for AML patients not eligible for standard myeloablative allo-SCT.

Comorbidity is an independent predictor of complete remission in elderly patients receiving induction chemotherapy for acute myeloid leukemia

Elderly patients with acute myeloid leukemia (AML) have a poor prognosis, which is explained by the disease itself and by host‐related factors. The objective of this study was to determine the prognostic role of comorbidities in this population.

Positron emission tomography response at the time of autologous stem cell transplantation predicts outcome of patients with relapsed and/or refractory Hodgkin’s lymphoma responding to prior salvage therapy

Background High-dose chemotherapy followed by autologous stem cell transplantation is the standard treatment for relapsed and/or refractory Hodgkin’s lymphoma although half of patients relapse after transplantation. Predictive factors, such as relapse within 12 months, Ann-Arbor stage at relapse, and relapse in previously irradiated fields are classically used to identify patients with poor outcome. Recently, 18-fluorodeoxyglucose positron emission tomography has emerged as a new method for providing information to predict outcome. The aim of this study was to confirm the predictive value of positron emission tomography status after salvage therapy and to compare single versus tandem autologous stem cell transplantation in patients with relapsed and/or refractory Hodgkin’s lymphoma. Design and Methods We report a series of 111 consecutive patients with treatment-sensitive relapsed and/or treatment-refractory Hodgkin’s lymphoma who achieved complete (positron emission tomography-negative group) or partial remission (positron emission tomography-positive group) at positron emission tomography evaluation after salvage chemotherapy and who underwent single or tandem autologous stem cell transplantation. Results Five-year overall and progression-free survival rates were 81% and 64%, respectively. There were significant differences in 5-year progression-free survival (79% versus 23%; P<0.001) and 5-year overall survival (90% versus 55%, P=0.001) between the positron emission tomography-negative and -positive groups, respectively. A complete response, as determined by positron emission tomography evaluation, after salvage therapy predicted significantly better 5-year overall survival rates in both intermediate (91% versus 50%; P=0.029) and unfavorable (89% versus 58%; P=0.026) risk subgroup analyses. In the positron emission tomography-positive subgroup, tandem transplantation improved 5-year progression-free survival from 0% (in the single transplantation group) to 43% (P=0.034). Multivariate analysis showed that positron emission tomography status (hazard ratio: 5.26 [2.57–10.73]) and tandem transplantation (hazard ratio: 0.39 [0.19–0.78]) but not risk factors at relapse (hazard ratio: 1.77 [0.80–3.92]) significantly influenced progression-free survival, while only tomography status significantly influenced overall survival (hazard ratio: 4.03 [1.38–11.75]). Conclusions In patients with relapsed/refractory Hodgkin’s lymphoma responding to prior salvage therapy, positron emission tomography response at time of autologous stem cell transplantation favorably influences outcome and enables identification of patients requiring single or tandem transplantation.

Reduced-intensity conditioning allogeneic SCT as salvage treatment for relapsed multiple myeloma

The aim of this retrospective analysis was to assess the benefit of reduced-intensity conditioning allo SCT (RIC allo-SCT) in a cohort of 32 relapsed multiple myeloma (MM) patients. A total of 19 patients had an HLA-identical sibling donor (‘donor’ group), while 13 patients had no donor (‘no-donor’ group). There were no significant differences between these two groups as for prognosis risk factors. Eighteen patients from the ‘donor’ group could actually proceed to RIC allo-SCT. With a median follow-up of 36 (range, 21–60) months, six patients died from transplant-related toxicity (cumulative incidence, 33% (95% CI, 11–55%)). Only 4 patients from the 18 transplanted patients (22%; 95% CI, 7–48%) progressed after RIC allo-SCT, as compared to 12 (86%; 95% CI, 56–98%; P=0.0003) among the nontransplanted patients. In an ‘intention-to-treat’ analysis, the Kaplan–Meier estimate of PFS was significantly higher in the ‘donor’ group as compared to the ‘no-donor’ group (P=0.01; 46 versus 8% at 3 years). There was no difference in terms of overall survival. However, in multivariate analysis, actual performance of RIC allo-SCT was associated with better PFS (relative risk, 0.35; 95% CI, 0.15–0.82; P=0.01). These data suggest a potential benefit for RIC allo-SCT in the management of relapsed MM warranting further prospective investigations.

Reduced intensity conditioning allogeneic stem cell transplantation for patients with acute myeloid leukemia: long term results of a ‘donor’ versus ‘no donor’ comparison

Reduced intensity conditioning allogeneic stem cell transplantation for patients with acute myeloid leukemia: long term results of a ‘donor’ versus ‘no donor’ comparison

Occurrence and severity of adverse events after autologous hematopoietic progenitor cell infusion are related to the amount of granulocytes in the apheresis product

BACKGROUND: Adverse events (AEs) after hematopoietic progenitor cell (HPC) infusion are rare but might be life‐threatening. These reactions have traditionally been associated with the amount of infused cryoprotectant, but persistence of such events after dimethyl sulfoxide (DMSO) depletion has questioned this assumption.

Identification of new classes among acute myelogenous leukaemias with normal karyotype using gene expression profiling

Conventional cytogenetic analysis currently stratifies acute myelogenous leukaemia (AML) into prognostically relevant groups. However, approximately 50% of adult AMLs have normal cytogenetics (NC-AMLs), and represent a heterogeneous and poorly understood group. We analysed gene expression in 55 AML samples including 53 cases from adult patients with NC-AML (n=36), trisomy 8, t(15;17), t(8;21), t(11;19), 7q deletion, and two cell lines using 9000-gene DNA microarrays. Global hierarchical clustering showed that NC-AMLs are a heterogeneous group. Supervised analysis distinguished two subgroups of NC-AML: one subgroup constituted a homogeneous NC cluster (‘pure NC-AML’), and the other NC-AMLs were close to the AML cases with translocations (‘translocation like’). Gene expression signatures were also derived for patients with trisomy 8, as well as FLT3 and MLL gene duplications. Importantly, samples from 24 NC-AML patients who could be evaluated for clinical outcome were analysed. In all, 43 genes that discriminated two classes of patients with significantly different prognosis were identified. The poor prognosis class contained a majority of ‘pure NC-AMLs’, whereas the ‘translocation-like’ AMLs were in the good prognosis class. Discriminator genes included genes involved in drug resistance (TOP2B), protein transport (MTX2, SLC35A2), and cell signalling (MAPK1, PRKAB2). Our results demonstrate the transcriptional heterogeneity of NC-AMLs, and suggest the existence of ‘translocation-like’ NC-AMLs and of a gene expression signature that may predict response to chemotherapy.

Mycophenolate mofetil and cyclosporine for graft-versus-host disease prophylaxis following reduced intensity conditioning allogeneic stem cell transplantation.

Summary:The use of reduced intensity conditioning (RIC) regimens for allogeneic stem cell transplantation (allo-SCT) can result in a significant decrease in early procedure-related toxicity in patients not eligible for standard myeloablative regimens. However, acute graft-versus-host disease (aGVHD) remains a matter of concern after RIC allo-SCT, and its incidence might be expected to be higher in elderly and high-risk patients. This report investigated mycophenolate mofetil (MMF) and cyclosporin A (CsA) combination (n=14) in comparison to CsA alone (n=20) for GVHD prophylaxis in cancer patients aged over 50 years (27 haematological malignancies and seven solid tumours) receiving an HLA-identical sibling antithymocyte-globulin (ATG)-based RIC allo-SCT. Baseline demographic characteristics and risk factors for aGVHD were comparable between both groups. Although MMF administration was not associated with any significant toxicity, the cumulative incidence of any form of GVHD was comparable between both groups (cumulative incidence of grade II–IV aGVHD, 50% (95% CI, 28–72%) for CsA alone, as compared to 64% (95% CI, 39–89%) to CsA and MMF, P=NS), suggesting that adjunction of MMF to CsA is feasible, but does not translate towards a significant reduction of aGVHD, at least in the context ATG-based RIC allo-SCT.

Brentuximab vedotin followed by allogeneic transplantation as salvage regimen in patients with relapsed and/or refractory Hodgkin's lymphoma.

Patients with relapsed or refractory Hodgkin lymphoma (RR‐HL) have poor outcomes. Brentuximab vedotin (BV), an antibody–drug conjugate comprising an anti‐CD30 antibody conjugated to the potent anti‐microtubule agent, monomethyl auristatin E, induces high tumour responses with moderate adverse effects. In a retrospective study, we describe objective response rates and subsequent allogeneic stem cell transplantation (allo‐SCT) in patients with RR‐HL treated by BV in a named patient program in two French institutions. Twenty‐four adult patients with histologically proven CD30+ RR‐HL treated with BV were included from July 2009 to November 2012. Response to BV treatment was evaluated after four cycles. Eleven patients were in complete response (45.8%), while five patients were in partial response (20.8%), with an overall response rate of 66.6%. Eight patients failed to respond to BV (33.3%). All of the responding patients could receive consolidation treatment after BV: three patients underwent autologous stem cell transplantation (auto‐SCT), three patients received a tandem auto‐SCT/allo‐SCT, nine patients received allo‐SCT and one patient was treated with donor lymphocyte infusion. We found no treatment‐related mortality at day 100 among the 12 patients who underwent BV following by allogeneic transplantation. With a median follow‐up of 20 months (range 10.5–43.2), none of them relapsed or died. BV followed by allo‐SCT represents an effective salvage regimen in patients with RR‐HL. Copyright

Nonmyeloablative conditioning, unmanipulated haploidentical SCT and post-infusion CY for advanced lymphomas

Allo-SCT is regularly performed in advanced lymphoma. Haploidentical family donors are a valuable source of hematopoietic stem cells and transplants from these donors, using T-repleted grafts, has recently been successfully reported. We report on 49 patients with refractory lymphoma who received T-repleted haploidentical SCT with a non-myeloablative regimen and post-transplant CY. The median time to recover ANC >0.5 × 10e9/L and transfusion independent plt count >20 × 10e9/L was 20 days (range 14–38) and 26 days (range 14–395). The probability to reach ANC >0.5 × 10e9/L at 30 days was 87% and transfusion independent plt count >20 × 10e9/L at 100 days was 87%. The cumulative incidence of grade 2–4 acute GVHD (aGVHD) was 25.6% (95% confidence interval (CI): 12.9–38.3%) and the cumulative incidence of chronic GVHD (cGVHD) was 5.2% (95% CI: 0–12.4%). The median follow-up is 20.6 months (range 12–54), and the projected 2-year OS and PFS were 71 and 63%. The relapse rate was 18.7% (95% CI: 7.6–29.8%) and the median time to relapse was 4.4 months (range 1.1–8.3). At 2 years, cumulative incidence of NRM was 16.3% (95% CI: 5.9–26.8%). T-repleted Haploidentical transplantation with post-infusion CY is a feasible and effective therapy in the poor prognosis of advanced lymphoma patients.