Different outcome of allogeneic transplantation in myelofibrosis using conventional or reduced-intensity conditioning regimens.
ABSTRACT Allogeneic haematopoietic stem cell transplantation remains the only curative treatment of myelofibrosis with myeloid metaplasia (MMM). Previous reports have indicated significant treatment-related mortality (TRM) for patients transplanted after myeloablative conditioning but superior survival has been reported after reduced-intensity conditioning (RIC). We report the results of a survey of all allogeneic transplantations for MMM performed in Sweden at six transplant units between 1982 and 2004. Twenty-seven patients were transplanted; 17 with a myeloablative conditioning regimen and 10 with RIC. The median age was 50 years (5-63 years) at transplantation. After a median follow up of 55 months, 20 patients are alive. TRM was 10% in the RIC group and 30% in the myeloablative group. There was no difference in survival for high or low-risk patients according to Cervantes score or between sibling and unrelated donor transplantations.
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ABSTRACT: To determine whether a difference in donor source affects the outcome of transplantation for patients with primary myelofibrosis (PMF), a retrospective study was conducted using the national registry data on patients who received first allogeneic hematopoietic cell transplantation (HCT) with related BM (n=19), related PBSCs (n=25), unrelated BM (n=28) or unrelated umbilical cord blood (UCB; n=11). The 5-year OS rates after related BM, related PBSC and unrelated BM transplantation were 63%, 43% and 41%, respectively, and the 2-year OS rate after UCB transplantation was 36%. On multivariate analysis, the donor source was not a significant factor for predicting the OS rate. Instead, performance status (PS) 2 (vs PS 0-1) predicted a lower OS (P=0.044), and RBC transfusion 20 times before transplantation (vs transfusion 9 times) showed a trend toward a lower OS (P=0.053). No advantage of nonmyeloablative preconditioning regimens in terms of decreasing nonrelapse mortality or increasing OS was found. Allogeneic HCT, and even unrelated BM and UCB transplantation, provides a curative treatment for PMF patients.Bone Marrow Transplantation advance online publication, 25 November 2013; doi:10.1038/bmt.2013.180.Bone marrow transplantation 11/2013; · 3.00 Impact Factor
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ABSTRACT: Allogeneic hematopoietic stem cell transplantation (HSCT) is the only potentially curative therapy for myelofibrosis. Despite improved outcomes, morbidity and mortality of HSCT remain high. Here we examine recent data on patient selection, timing, and outcomes of HSCT in myelofibrosis. While there is a general effort to restrict HSCT to transplant-eligible intermediate-2 and high-risk patients, this group has comparatively worse HSCT outcomes, largely driven by their high transplant-related mortality (TRM). When adjusted for age, reduced intensity conditioning (RIC) has shown superior outcomes compared with myeloablative conditioning (MAC), making RIC-HSCT a viable option for older patients. Emerging concepts include the use of ruxolitinib pretransplant, optimizing MAC to decrease toxicity, and use of posttransplant JAK2-mutant allele burden to guide prophylactic immunotherapy to prevent relapse. The recognition of prognostic significance of somatic mutations in the ASXL1, EZH2, SRSF2, and IDH1/2 genes, and the improved assessment of risk of leukemic transformation have added a new dimension to risk stratification. Improving our understanding of molecular genetics and leukemic transformation holds promise for more precise patient selection for HSCT. Although RIC-HSCT may reduce TRM, further studies are needed to optimize conditioning regimens and to define the optimal timing of HSCT.Current opinion in hematology 12/2013; · 5.19 Impact Factor
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ABSTRACT: Myeloproliferative neoplasms are a diverse group of disorders that can have prolonged chronic phases, but eventually accelerate and can transform to a secondary acute myeloid leukemia that is ultimately fatal. Triapine is a novel ribonucleotide reductase inhibitor of the M2 subunit. Sequential inhibition of ribonucleotide reductase with triapine and an M1 ribonucleotide reductase inhibitor (fludarabine) was noted to be safe, and led to a 29% complete plus partial response rate in myeloproliferative neoplasms. This manuscript reports a phase 2 trial of triapine (105 mg/m2/day) followed by fludarabine (30 mg/m2/day) daily for 5 consecutive days in 37 patients with accelerated myeloproliferative neoplasms and secondary acute myeloid leukemia. The overall response rate was noted to be 49% (18/37), with a complete remission rate of 24% (9/37). Overall response rates and complete remissions were seen in all disease subsets, including secondary acute myeloid leukemia, where the overall response rate and complete remission rate was 48% and 33%, respectively. All patients with known JAK2 V617F mutations (6/6) responded. The median overall survival of the entire cohort was 6.9 months, with a median overall survival of both overall responders and complete remissions of 10.6 months. These data further demonstrate the promise of simultaneous inhibition of ribonucleotide reductase in patients with accelerated myeloproliferative neoplasms and secondary acute myeloid leukemia. This study was registered with clinical trials.gov (NCT00381550).Haematologica 12/2013; · 5.94 Impact Factor