Allogeneic stem cell transplantation after reduced-intensity conditioning in patients with myelofibrosis: a prospective, multicenter study of the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation

Kröger, Nicolaus; Holler, Ernst; Kobbe, Guido; Bornhäuser, Martin; Schwerdtfeger, Rainer; Baurmann, Herrad; Nagler, Arnon; Bethge, Wolfgang; Stelljes, Matthias; Uharek, Lutz; Wandt, Hannes; Burchert, Andreas; Corradini, Paolo; Schubert, Jörg; Kaufmann, Martin; Dreger, Peter; Wulf, Gerald; Einsele, Hermann; Zabelina, Tatjana; Kvasnicka, Hans Michael; Thiele, Jürgen; Brand, Ronald; Zander, Axel R.; Niederwieser, Dietger; Witte, Theo M. de

doi:10.1182/blood-2009-07-234880

Cited by 366 publications

(453 citation statements)

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“…Except for allo-HSCT [7,8], the therapy of MF remains essentially palliative and is usually adjusted to the characteristics of the disease in every individual [6]. Thus, a wait-and-see approach is often adopted in asymptomatic patients, delaying treatment start until a change in the clinical situation is observed.…”

Section: Discussionmentioning

confidence: 99%

“…Except for allogeneic hemopoietic stem cell transplantation (allo-HSCT) [7,8], therapy of MF remains mostly palliative and is usually adjusted to the disease characteristics in each patient [6]. In the "hyperproliferative" forms of the disease, characterized by constitutional symptoms, marked splenomegaly, leukocytosis and/or thrombocytosis, and, more rarely, aquagenic pruritus or bone pain, cytolytic treatment is usually administered [6].…”

Section: Introductionmentioning

confidence: 99%

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Efficacy and tolerability of hydroxyurea in the treatment of the hyperproliferative manifestations of myelofibrosis: results in 40 patients

et al. 2010

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Hydroxyurea (HU) is frequently given as treatment for myelofibrosis (MF), but data on its efficacy and tolerability are scarce. The results of HU therapy were evaluated in 40 patients with hyperproliferative manifestations of primary (n= 32), post-polycythemia vera (n= 6) or post-essential thrombocythemia (n= 2) myelofibrosis. Median interval between diagnosis and HU start was 6.2 months (range: 0-141.7). Reasons for treatment were: constitutional symptoms (55%), symptomatic splenomegaly (45%), thrombocytosis (40%), leukocytosis (28%), pruritus (10%), and bone pain (8%). The starting dose was 500 mg/day, subsequently adjusted to the individual efficacy and tolerability.Response was: bone pain 100%, constitutional symptoms 82%, pruritus 50%, splenomegaly 40%, and anemia 12.5%. According to the International Working Group for Myelofibrosis Research and Treatment criteria, clinical improvement was achieved in 16 patients (40%). Median duration of response was 13.2 months (range: 3-126.2). Worsening of the anemia or appearance of pancytopenia were observed in 18 patients, requiring administration of erythropoietin-stimulating agents (n=17) and/or danazol (n=9). Oral or leg ulcers appeared in 5 patients and one had gastrointestinal symptoms. HU is an effective and generally well-tolerated therapy for the hyperproliferative manifestations of MF. The accentuation of the anemia often induced by HU is usually manageable with concomitant treatment.Response to Reviewers: Answers to the comments by reviewer 1:1. Retrospective design of the study. As already stated in the Introduction and in the Discussion, although there is limited bibliographic support for the use of hydroxyurea (HU) in MF, in clinical practice, this drug has been considered for many years (and still is) as the standard therapy for the hyperproliferative manifestations of this disease. Actually, until the recent development of the JAK2 inhibitors, no real alternative therapy to HU was available for comparison. As a result, for the time being, a retrospective study is the only possibility to assess the efficacy and tolerability of HU in MF.Having said this, it must be remarked that the data from the present study have been generated in a single institution, in which the drug was used following uniform rules for the starting dose, the dose adjustments and the use of adjuvant drugs for the treatment of the associated anemia. Moreover, more than 80% of the patients in the study were treated by the same physician, with long-lasting and specific dedication to MF.2. Selection of the patients. As stated in the Patients and Methods, the 40 patients included in the study were the only ones receiving HU among the 157 with MF followed in our institution during the study period. As also stated in the same section, HU was given to these 40 patients exclusively as a treatment for the hyperproliferative manifestations of MF (i.e., constitutional symptoms, symptomatic splenomegaly, pruritus, bone pain, leukocytosis, and thrombocytosis). This means that a patient ...

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Efficacy and tolerability of hydroxyurea in the treatment of the hyperproliferative manifestations of myelofibrosis: results in 40 patients

et al. 2010

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“…RIC is associated with a lower NRM, but a higher risk of relapse, compared with standard myeloablative conditioning, and the current results suggest a qualified success (Table 1). [17][18][19][20][21] The notion of using ruxolitinib in order to reduce constitutional symptoms and splenomegaly prior to allo-SCT appears attractive. What is not known is the drug's impact on short-and long-term outcomes following allo-SCT; nor is the precise timing of allo-SCT or the role of allo-SCT-specific prognostic and predictive scores in the JAK-inhibitor era known.…”

Section: Introductionmentioning

confidence: 99%

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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“…More recently, Kroger et al reported the results of a prospective study of RIC allogeneic HSCT as treatment for 103 patients with myelofibrosis [29]. The conditioning regimen consisted in busulfan (10 mg/kg), fludarabine and ATG.…”

Section: Myelodysplastic Syndromes and Myeloproliferative Disordersmentioning

confidence: 99%

Allogeneic hematopoietic stem cell transplantation (HSCT) after reduced intensity conditioning

Servais¹,

Baron²,

Béguin³

2011

Transfusion and Apheresis Science

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a b s t r a c tAllogeneic hematopoietic stem cell transplantation (HSCT) following myeloablative (conventional) conditioning regimen is associated with a high incidence of transplant-related morbidity and mortality, limiting its use to younger patients without medical co-morbidities. Over the past few years, it has become more evident that the alloreactivity of transplanted donor immunocompetent cells against host tumor cells (graft-versus-tumor effects, GVT effects) plays a major role in eradicating malignancies after allogeneic HSCT. Based on these observations, several groups of investigators have developed reduced intensity conditioning (RIC) regimens allowing patients who are ineligible for conventional HSCT to benefit from the potentially curative GVT effects of allogeneic transplantation. Retrospective studies have suggested that, in comparison with myeloablative allogeneic HSCT, in patients aged 40-60 years, RIC HSCT was associated with a higher risk of relapse but a lower incidence of transplant-related mortality leading to similar progression-free and overall survivals. Prospective studies are ongoing to define which patients might most benefit from RIC HSCT, and to increase the anti-tumoral activity of the procedure while reducing the incidence and the severity of acute graft-versus-host disease (GVHD). In this article, we review the current status and perspectives of RIC HSCT.

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Allogeneic stem cell transplantation after reduced-intensity conditioning in patients with myelofibrosis: a prospective, multicenter study of the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation

Cited by 366 publications

References 22 publications

Efficacy and tolerability of hydroxyurea in the treatment of the hyperproliferative manifestations of myelofibrosis: results in 40 patients

Efficacy and tolerability of hydroxyurea in the treatment of the hyperproliferative manifestations of myelofibrosis: results in 40 patients

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

Allogeneic hematopoietic stem cell transplantation (HSCT) after reduced intensity conditioning

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