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2024-01-19T17:03:58.000Z

EBMT/ELN updated recommendations for allo-HSCT in myelofibrosis

Jan 19, 2024
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Learning objective: After reading this article, learners will be able to cite key updates in the new European Group for Blood and Marrow Transplantation/European LeukemiaNet recommendations for allogeneic hemopoietic stem cell transplantation in myelofibrosis.

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In 2015, the European Group for Blood and Marrow Transplantation (EBMT) and European LeukemiaNet (ELN) co-developed consensus-based guidelines for the indication and management of allogeneic hemopoietic stem cell transplantation (allo-HSCT) in myelofibrosis (MF). Since then, new therapies and combination treatments, improvements in patient/donor selection, conditioning regimens, and posttransplant supportive care have enabled an increased proportion of patients to access the potentially curative option of stem cell transplantation. However, these treatment advances have created new challenges, with the optimal management strategies for MF still unclear. To address this, the EBMT/ELN working group has reviewed data from 2015–2022 and revised the 2015 recommendations to optimize the use of allo-HSCT in patients with MF. Here, we summarize the key updates.

Study design1

  • Data was reviewed by a 26-member expert panel
  • Recommendations were consensus-based, and not derived from systematic reviews and evidence grading
  • The expert panel agreed on seven areas of major concern and rank-ordered 18 key clinical questions
  • Each recommendation required 80% of votes in favor for final inclusion

Patient selection and timing1

  • Over the past two decades, several prognostic tools have been developed for primary MF
  • These models have been extremely useful in predicting outcomes in patients with key high-risk mutations and clinical features
  • Recommendations for allo-HSCT according to prognostic model scores are shown in Figure 1

Figure 1. Prognostic model scores and allo-HSCT recommendations* 

Allo-HSCT, allogeneic hemopoietic stem cell transplantation; DIPSS, Dynamic International Prognostic Scoring System; MIPSS70, Mutation-Enhanced International Prognostic Scoring System 70; MTSS, Myelofibrosis Transplant Scoring System; PMF, primary myelofibrosis; RR6, response to ruxolitinib after 6 months model; SMF, secondary myelofibrosis.
*Adapted from Kroger, et al.1

Pretransplant management1

  • Pretransplant management techniques are highly important to ensure the best outcomes
  • Management techniques recommended for patients before transplant are shown in Figure 2

Figure 2. Pretransplant management recommendations* 

BP, blast phase; JAKi, Janus kinase inhibitor; SVT, splanchnic vein thrombosis.
*Adapted from Kroger, et al.1

 Donor selection, stem cell source/dose, and conditioning regimen1

  • Donor type is considered a significant predictor of transplant-related mortality
  • As a result of no current randomized comparisons, peripheral blood remains the preferred stem cell source compared with bone marrow grafts
  • Conclusive evidence surrounding optimal conditioning regimens remains scarce
  • Recommendations surrounding these clinical areas are highlighted in Figure 3

Figure 3. Recommendations for donor selection, stem cell source/dose, and conditioning regimen* 

ATG, anti-thymocyte globulin; ATLG, anti-T lymphocyte globulin; GvHD, graft-versus-host disease; HLA, human leukocyte antigen; PTCy, posttransplant cyclophosphamide.
*Adapted from Kroger, et al.1

 Posttransplant management1

  • Posttransplant management remains another key area of clinical importance
  • Effective management at this stage can reduce the risk of poor graft function, molecular relapse, and the need for a second transplant
  • Recommendations for posttransplant management are shown in Figure 4

Figure 4. Recommendations for posttransplant management* 

CR, complete remission; EBMT, European Group for Blood and Marrow Transplantation; GCSF, granulocyte colony-stimulating factor; GvHD, graft-versus-host disease; HLA, human leukocyte antigen; JAKi, Janus kinase inhibitor; MRD, measurable residual disease.
*Adapted from Kroger, et al.1

 Conclusion1

There is a lack of evidence from randomized trials regarding the optimal indication and management of allo-HSCT in MF; current recommendations are limited by retrospective analyses. However, the expert panel of the EBMT/ELN International Working Group comprises members from leading clinical centers, offering updated recommendations to assist clinicians and patients in optimizing allo-HSCT in MF. These guidelines aim to improve clinical outcomes and guide future processes in the absence of evidence-based guidance.

  1. Kroger N, Bacigalupo A, Barbui T, et al. Indication and management of allogeneic haematopoietic stem-cell transplantation in myelofibrosis: updated recommendations by the EBMT/ELN International Working Group. Lancet Haematol. 2023;11(1):e62-74. DOI: 1016/S2352-3026(23)00305-8

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