Allogeneic Stem Cell Transplantation for Myelofibrosis in 2012

McLornan, Donal; Mead, Adam J.; Jackson, Graham; Harrison, Claire

doi:10.1111/j.1365-2141.2012.09107.x

Cited by 51 publications

(41 citation statements)

References 73 publications

(89 reference statements)

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“…On this topic, conflicting results have been reported and this uncertainty may be partly due to the retrospective design of most studies which have been highly heterogeneous regarding selection of patients, drugs used in the conditioning, donor type and stem cell source. 8,11,12,25,28 Therefore, although many results would suggest the use of a busulfan-based conditioning regimen 10,25,29 as most appropriate, this issue remains a matter of debate and of intense clinical investigation. Other factors, including initial diagnosis (PV versus ET), presence or absence of the JAK2V617F mutation, patient/donor cytomegalovirus status, disease status at transplantation, stem cell source and T-cell depletion, had no influence on clinical outcome in our cohort of patients.…”

Section: Continued In the Next Columnmentioning

confidence: 99%

Allogeneic hematopoietic stem cell transplantation in patients with polycythemia vera or essential thrombocythemia transformed to myelofibrosis or acute myeloid leukemia: a report from the MPN Subcommittee of the Chronic Malignancies Working Party of the European Group for Blood and Marrow Transplantation

et al. 2014

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Section: Continued In the Next Columnmentioning

confidence: 99%

Allogeneic hematopoietic stem cell transplantation in patients with polycythemia vera or essential thrombocythemia transformed to myelofibrosis or acute myeloid leukemia: a report from the MPN Subcommittee of the Chronic Malignancies Working Party of the European Group for Blood and Marrow Transplantation

et al. 2014

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“…However, it is currently unknown which type of conditioning leads to the best outcome. 1 Although myeloablative conditioning resulted in considerable overall survival (OS) rates of 47-61% at 5 years, treatment-related mortality (TRM)/non-relapse mortality rates were high, ranging from 27 to 48% at 1-5 years. [2][3][4][5][6][7][8][9] The introduction of non-myeloablative-(NMA) and reduced-intensity conditioning (RIC) 10 regimens resulted in a lower TRM/non-relapse mortality rate of 16-30% at 1-5 years, with similar OS rates (31-67% after 3-5 years).…”

Section: Introductionmentioning

confidence: 99%

Effect of conditioning regimens on graft failure in myelofibrosis: a retrospective analysis

Slot

Smits

Donk

et al. 2015

Bone Marrow Transplant

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In myelofibrosis, the introduction of reduced-intensity conditioning (RIC) preceding allogeneic stem cell transplantation (SCT) resulted in lower transplant-related mortality rates compared with myeloablative conditioning. However, lowering the intensity of conditioning may increase the risk of graft failure in myelofibrosis, although hitherto this has not been indisputably proven. We here report the outcome of 53 patients who underwent allogeneic SCT with different conditioning regimens (RIC and nonmyeloablative (NMA)) in three transplantation centers in the Netherlands. The cumulative incidence of graft failure within 60 days after SCT was high (28%), and this was primarily associated with the intensity of the conditioning regimen. Cumulative neutrophil engraftment at 60 days was lower in patients who received NMA conditioning compared with those who received RIC (56% vs 84%, P = 0.03). Furthermore, of six patients who received a second transplantation after graft failure, the three patients with RIC regimens subsequently engrafted, whereas the three patients who received a second NMA regimen did not. This study indicates that in myelofibrosis, NMA regimens result in high engraftment failure rates. We propose the use of more intensive conditioning regimens, incorporating busulfan or melphalan.

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“…2 Allogeneic hematopoietic stem cell transplantation is currently the only treatment option that has curative potential in myelofibrosis. 5 However, allogeneic transplantation is associated with significant morbidities, and most patients are not suitable candidates. Additionally, with the exception of allogeneic hematopoietic stem cell transplantation, no therapy has consistently been associated with stabilization or resolution of fibrosis in patients with myelofibrosis.…”

Section: Introductionmentioning

confidence: 99%

Resolution of bone marrow fibrosis in a patient receiving JAK1/JAK2 inhibitor treatment with ruxolitinib

et al. 2013

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© F e r r a t a S t o r t i F o u n d a t i o n 2 0 1 3prior to enrollment of patients and the study was conducted in accordance with the principles set forth by the Declaration of Helsinki. ResultsA 74-year old male patient presented to our clinic with constitutional symptoms (night sweats and fever), pruritus, and marked splenomegaly of 26 cm below the left costal margin (spleen volume: 3390 cm 3 ). He had received a diagnosis of PV 10 years previously, in 1999, and had been receiving treatment with hydroxycarbamide since the initial diagnosis. Comorbidities included hypertension and monoclonal gammopathy, both of which were found at the time the PV was diagnosed.A diagnosis of post-PV myelofibrosis was confirmed, the patient was assigned to the intermediate-2 risk category on the basis of International Prognostic Scoring System (IPSS) criteria 3 (age >65 years and presence of constitutional symptoms), and he was enrolled in the COMFORT-II trial 6 at a starting dose of ruxolitinib 15 mg bid (platelet count at baseline: 138x10 9 /L). His initial hemoglobin level was 140 g/L, and his white blood cell count was 15.6x10 9 /L. At screening, the patient was found to be JAK2 V617F-positive. Cytogenetic analysis showed an additional abnormality of 46,XY,der (22) After the initiation of ruxolitinib treatment, the pateint's splenomegaly improved dramatically (Figure 1): a 30% reduction in palpable spleen length was observed at week 4 (the first spleen assessment). However, the patient became mildly thrombocytopenic (Figure 2) with a platelet count of 86x10 9 /L, and the dose of ruxolitinib was reduced to 10 mg bid as per study protocol. Platelet counts recovered with this dose reduction, and the patient has remained on treatment at a dose of 10 mg bid. At this dose, splenomegaly progressively resolved. The smallest palpable spleen length measurement, 2 cm (a 90% reduction from baseline), was recorded after 108 weeks of ruxolitinib treatment. The patient was classified as having a spleen response, as defined per protocol, with a 42% reduction in spleen volume at week 24, a 58% reduction at week 48, and a 75% reduction at the latest assessment by magnetic resonance imaging at week 144 ( Figure 3). In terms of symptoms, both fatigue and intractable pruritus were present at study entry; within 48 h of the initiation of ruxolitinib treatment, the pruritus had resolved (and has remained negligible) and the fatigue had improved markedly. After 168 weeks of ruxolitinib treatment, morphological analysis of the bone marrow indicated a significant improvement (Figure 4). At the pre-trial baseline assessment in 2009, analysis of hematoxylin and eosin-stained trephine core sections showed maximally increased cellularity with disordered hematopoiesis and pleomorphic megakaryocytes, most of which were large and had abnormally lobated nuclei. Many formed tight clusters, and CD61 immunohistochemical analysis (highlighting megakaryocytes and platelets) emphasized the increase, pleomorphism, and clustering. There was a diffus...

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Allogeneic Stem Cell Transplantation for Myelofibrosis in 2012

Cited by 51 publications

References 73 publications

Effect of conditioning regimens on graft failure in myelofibrosis: a retrospective analysis

Resolution of bone marrow fibrosis in a patient receiving JAK1/JAK2 inhibitor treatment with ruxolitinib

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