Allogeneic stem cell transplantation for myeloproliferative neoplasm in blast phase

Cherington, Chad; Slack, James L.; Leis, José F.; Adams, Roberta H.; Reeder, Craig B.; Mıkhael, Joseph; Camoriano, John; Noël, Pierre; Fauble, Veena; Betcher, Jeffrey; Higgins, Meagan S.; Gillette-Kent, Ginger; Tremblay, Lisa D.; Peterson, Mary; Olsen, Jane; Tibes, Raoul; Mesa, Ruben A.

doi:10.1016/j.leukres.2012.04.021

Cited by 42 publications

(26 citation statements)

References 43 publications

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“…[85][86][87][88] Current efforts are investigating diverse agents, including hypomethylating agents, JAK and MEK inhibitors, BCL-X L and BCL-2 inhibitors and clofarabine. [89][90][91][92][93][94] IMPACT OF THE TRANSPLANT-PROCEDURE-AND DONOR-RELATED FACTORS Several prospective multicenter studies have now confirmed the usefulness of RIC-SCT using related or unrelated donors for younger and older patients with MF. In a large retrospective European Group for Blood and Marrow Transplantation study, outcomes from 250 consecutive patients (median age 56 years) with PPV-MF (n = 120) or PET-MF (n = 130) who received allo-SCT, either in MF 'chronic' phase (n = 193) or MF transformed to AML (n = 57), were analyzed.…”

Section: Impact Of Targeting the Jak/signal Transducers And Activatormentioning

confidence: 96%

Allo-SCT for myelofibrosis: reversing the chronic phase in the JAK inhibitor era?

Tamari

Mughal

Rondelli

et al. 2015

Bone Marrow Transplant

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At present, allogeneic hematopoietic stem cell transplantation (allo-SCT) is the only curative treatment for patients with myelofibrosis (MF). Unfortunately a significant proportion of candidate patients are considered transplant ineligible due to their poor general condition and advanced age at time of diagnosis. The approval of the first JAK inhibitor, Ruxolitinib, for patients with advanced MF in 2011 has had a qualified impact on the treatment algorithm. The drug affords substantial improvement in MF-associated symptoms and splenomegaly but no major effect on the natural history. There has, therefore, been considerable support to assess the drug’s candidacy in the peri-transplant period. The drug’s precise impact on clinical outcome following allo-SCT is currently not known; nor is the drug’s long term efficacy and safety known. Considering the rarity of MF and the small proportion of patients who are undergoing allo-SCT, well designed collaborative efforts are required. In order to address some of the principal challenges, an expert panel of laboratory and clinical experts in this field was established, and an independent workshop held during the 54th American Society of Hematology’s meeting in New Orleans, USA, on 6th December 2013 and the European Hematology Association meeting in Milan, Italy on 13th June 2014. This document summarizes the results of these efforts.

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Section: Impact Of Targeting the Jak/signal Transducers And Activatormentioning

confidence: 96%

Allo-SCT for myelofibrosis: reversing the chronic phase in the JAK inhibitor era?

Tamari

Mughal

Rondelli

et al. 2015

Bone Marrow Transplant

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“…There is mounting evidence to support this approach in MPN blast phase as well. 64 For patients not deemed to be allo-SCT candidates or those in whom allo-SCT may be delayed, it is our opinion that ruxolitinib be initiated or that the patient be considered for enrollment into a JAK2 inhibitor trial. In our experience, using current US labeling recommendations for the ruxolitinib starting dose may lead to anemia or thrombocytopenia in patients with compromised baseline values (ie, hemoglobin ,10 g/dL regardless of platelet count).…”

Section: Mfmentioning

confidence: 99%

Therapy for myeloproliferative neoplasms: when, which agent, and how?

Geyer¹,

Mesa

2014

Blood

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Myeloproliferative neoplasms, including polycythemia vera (PV), essential thrombocythemia, and myelofibrosis (MF) (both primary and secondary), are recognized for their burdensome symptom profiles, life-threatening complications, and risk of progression to acute leukemia. Recent advancements in our ability to diagnose and prognosticate these clonal malignancies have paralleled the development of MPN-targeted therapies that have had a significant impact on disease burden and quality of life. Ruxolitinib has shown success in alleviating the symptomatic burden, reducing splenomegaly and improving quality of life in patients with MF. The role and clinical expectations of JAK2 inhibition continues to expand to a variety of investigational arenas. Clinical trials for patients with MF focus on new JAK inhibitors with potentially less myelosuppression (pacritinib) or even activity for anemia (momelotinib). Further efforts focus on combination trials (including a JAK inhibitor base) or targeting new pathways (ie, telomerase). Similarly, therapy for PV continues to evolve with phase 3 trials investigating optimal frontline therapy (hydroxyurea or IFN) and second-line therapy for hydroxyurea-refractory or intolerant PV with JAK inhibitors. In this chapter, we review the evolving data and role of JAK inhibition (alone or in combination) in the management of patients with MPNs.

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“…2 At present, the best outcomes in this patient population appear to be restricted to those few individuals who have undergone allogeneic hematopoietic cell transplantation (HCT). 2,[6][7][8][9] However, the available data addressing the efficacy of this approach are limited not only by the small number of reported patients, but also by the heterogeneity of the clinical status of those individuals who underwent transplant.…”

Section: Introductionmentioning

confidence: 99%

Treatment outcomes following leukemic transformation in Philadelphia-negative myeloproliferative neoplasms

Kennedy

Atenafu

Messner

et al. 2013

Blood

122

105

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Key Points• Induction followed by allotransplantation can achieve long-term disease control in select patients with AML arising from a Ph-MPN.• In this population, transplant should be the goal in patients treated with curative intent, as induction alone provides limited benefit.Leukemic transformation (LT) is a rare but fatal complication of Philadelphia-negative myeloproliferative neoplasms (MPNs) for which optimal treatment strategies are not known. At our center, we have adopted a treatment approach for LT where patients within the transplant age group who have a reasonable fitness level are treated with curative intent and offered induction chemotherapy. Subsequently, those who respond and have a suitable donor are considered for allogeneic hematopoietic cell transplantation (HCT). In this study, we evaluated the clinical outcomes of this treatment approach in 75 patients with LT. The 2-year overall survival (OS) from the time of LT was 15%. A total of 39 patients (52%) were treated with curative intent (induction 6 HCT) and had a 2-y OS of 26% compared with 3% in those noncuratively treated (P < .0001). In the curative intent group, 18 individuals (46%) achieved complete remission (CR) or CR with incomplete recovery and 12 (31%) reverted to a chronic MPN phase, with 17 patients undergoing HCT. Survival of patients posttransplant was significantly improved compared with those who responded to induction but were not transplanted (2-y OS of 47% vs 15%; P 5 .03). Thus, induction chemotherapy followed by HCT has the potential for long-term disease control in select patients with LT preceded by a MPN.

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Allogeneic stem cell transplantation for myeloproliferative neoplasm in blast phase

Cited by 42 publications

References 43 publications

Allo-SCT for myelofibrosis: reversing the chronic phase in the JAK inhibitor era?

Allo-SCT for myelofibrosis: reversing the chronic phase in the JAK inhibitor era?

Therapy for myeloproliferative neoplasms: when, which agent, and how?

Treatment outcomes following leukemic transformation in Philadelphia-negative myeloproliferative neoplasms

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