The role of allogeneic SCT in primary myelofibrosis: a British Society for Blood and Marrow Transplantation study

Stewart, Wendy A.; Pearce, Rachel; Kirkland, Keiren; Bloor, Adrian; Thomson, Kirsty; Apperley, Jane F.; McQuaker, Grant; Marks, DI; Craddock, Charles; McCann, Shaun R.; Russell, NH; Cook, Gordon; Kottaridis, PD

doi:10.1038/bmt.2010.14

Cited by 67 publications

(58 citation statements)

References 28 publications

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“…It is well appreciated that hematopoietic recovery is faster in splenectomized patients. [19][20][21] Thus, pretreatment with ruxolitinib might actually facilitate both engraftment and hematological recovery after allogeneic HCT through the reduction in cytokine levels and splenomegaly.…”

Section: Discussionmentioning

confidence: 99%

Allogeneic hematopoietic cell transplantation for myelofibrosis in patients pretreated with the JAK1 and JAK2 inhibitor ruxolitinib

Jaekel

Behre

Behning

et al. 2013

Bone Marrow Transplant

103

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The Janus-activated kinase 1 (JAK1) and JAK2 inhibitor ruxolitinib is effective in decreasing symptomatic splenomegaly and myelofibrosis (MF)-related symptoms. However, allogeneic hematopoietic cell transplantation (HCT) remains the only curative option. We evaluated the impact of ruxolitinib on the outcome after HCT. A cohort of 14 patients (median age 58 years) received a subsequent graft from related (n ¼ 3) and unrelated (n ¼ 11) donors after a median exposure of 6.5 months to ruxolitinib. At HCT, MF risk for survival according to the International Prognostic Scoring System was intermediate-2 or high risk in 86% of patients. Under ruxolitinib, MF-related symptoms were ameliorated in 10 (71.4%) patients and the palpable spleen reduced by a median of 41% in 7 (64%) of 11 patients with splenomegaly. Engraftment occurred in 13 (93%) patients. Acute GvHD grade-III occurred in 2 (14%) patients. Median follow-up was 9 months. Survival, EFS and treatment-related mortality were 78.6, 64 and 7%, respectively. Through the anti-JAK-mediated reduction in both cytokines and splenomegaly as well as improvement in performance status, ruxolitinib might improve outcome after allogeneic HCT in patients with MF. The downregulation of inflammatory cytokines might have a beneficial impact on graft failure and acute GvHD.

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Section: Discussionmentioning

confidence: 99%

Allogeneic hematopoietic cell transplantation for myelofibrosis in patients pretreated with the JAK1 and JAK2 inhibitor ruxolitinib

Jaekel

Behre

Behning

et al. 2013

Bone Marrow Transplant

103

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“…Patients treated with BUCY, with targeting of BU dose, had a 5-year OS of 68%, compared to 46% in non-targeted regimens (Deeg et al, 2003;Kerbauy et al, 2007;Zang & Deeg, 2009). Treatmentrelated mortality (TRM) at 1 year following MA HSCT ranged from 16% to 48%, with better outcomes seen in recipients of stem cells from human leucocyte antigen (HLA)-matched related donors (Guardiola et al, 1999;Daly et al, 2003;Ditschkowski et al, 2004;Kerbauy et al, 2007;Ballen et al, 2010;Stewart et al, 2010;Abelsson et al, 2011). OS !…”

Section: Myeloablative Hsctmentioning

confidence: 99%

Guideline for the diagnosis and management of myelofibrosis

et al. 2012

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SummaryThe guideline group regarding the diagnosis and management of myelofibrosis was selected to be representative of UK-based medical experts, together with a contribution from a single expert from the USA. MEDLINE and EMBASE were searched systematically for publications in English from 1966 until August 2011 using a variety of key words. The writing group produced the draft guideline, which was subsequently revised by consensus of the members of the General Haematology and Haemato-oncology Task Forces of the British Committee for Standards in Haematology (BCSH). The guideline was then reviewed by a sounding board of UK haematologists, the BCSH and the British Society for Haematology Committee and comments incorporated where appropriate. The criteria used to state levels and grades of evidence are as outlined in the Procedure for Guidelines commissioned by the BCSH; the 'GRADE' system was used to score strength and quality of evidence. The objective of this guideline is to provide healthcare professionals with clear guidance on the investigation and management of primary myelofibrosis, as well as post-polycythaemic myelofibrosis (post-PV MF) and post-thrombocythemic myelofibrosis (post-ET MF) in both adult and paediatric patients.

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“…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). 2,6,9,[11][12][13] However, randomized prospective data comparing myeloablative with RIC/NMA conditioning are lacking.…”

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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The role of allogeneic SCT in primary myelofibrosis: a British Society for Blood and Marrow Transplantation study

Cited by 67 publications

References 28 publications

Allogeneic hematopoietic cell transplantation for myelofibrosis in patients pretreated with the JAK1 and JAK2 inhibitor ruxolitinib

Allogeneic hematopoietic cell transplantation for myelofibrosis in patients pretreated with the JAK1 and JAK2 inhibitor ruxolitinib

Guideline for the diagnosis and management of myelofibrosis

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

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