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Allogeneic Hematopoietic Stem Cell Transplantation in Myelofibrosis: for Whom, When and How

Year: 2025
Type: article
Abstract: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only curative option for patients with myelofibrosis (MF). Its use, however, is restricted to carefully selected candidates due to the substantial risk of non-relapse mortality (NRM) and post-transplant complications. Optimal patient selection and timing therefore represent critical challenges in clinical practice.1 Risk stratification models such as DIPSS, MIPSS70 and MYSEC-PM identify patients with intermediate- or high-risk disease as potential transplant candidates. For these patients, tools such as the MTSS and the EBMT AI-AlloStratifier, together with additional biological factors, allow further refinement of eligibility.2,3 The timing of transplantation must balance the risk of disease worsening and MF-related complications against NRM. Transplantation should be pursued early in all eligible high-risk patients, while in lower-risk disease it may be deferred until clinical worsening with risk score escalation, symptomatic progression, or inadequate response to JAK inhibitors becomes evident (Figure 1). In the transplant context, JAK inhibitors play a pivotal role as a bridge to transplantation, reducing splenomegaly, improving symptom burden, and potentially enhancing transplant outcomes. In non-responsive patients with massive splenomegaly (particularly those with spleen size ≥15 cm below the left costal margin), splenectomy and/or splenic irradiation may be considered depending on center expertise.4,5 With regard to transplant modality, matched donors remain preferred; however, haploidentical transplantation with post-transplant cyclophosphamide has significantly expanded donor availability with encouraging results.6 Conditioning strategies range from myeloablative to reduced-intensity regimens, the latter being particularly suitable for older or comorbid patients. Novel approaches, including double alkylating regimens and treosulfan-based conditioning, show promise in improving engraftment and reducing toxicity.7,8 Furthermore, post-transplant management of measurable residual disease through tailored immunosuppression, donor lymphocyte infusion (DLI), and combined strategies is crucial to optimize outcomes.9 In conclusion, allo-HSCT should be offered to MF patients with poor prognosis according to validated scoring systems, ideally performed at a time when disease control is achieved. Advances in donor availability, conditioning regimens, and supportive strategies have improved survival, yet individualized, patient-centered decision-making remains fundamental.10 Figure 1. Transplant decision-making process for tailoring treatment in MF. DIPSS: Dynamic International Prognostic Score System; MIPSS70: Molecular International Prognostic Score System; MYSEC-PM: Myelofibrosis Secondary Prognostic Model; MTSS: Myelofibrosis Transplant Scoring System; MF-ARS: Myelofibrosis Allo-Stratifier Score. References 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 2024; 11(1): e62-e74. 2. Gagelmann N, Ditschkowski M, Bogdanov R, et al. Comprehensive clinical-molecular transplant scoring system for myelofibrosis undergoing stem cell transplantation. Blood 2019; 133(20): 2233-42. 3. Hernandez-Boluda JC, Mosquera-Orgueira A, Gras L, et al. Use of machine learning techniques to predict poor survival after hematopoietic cell transplantation for myelofibrosis. Blood 2025; 145(26): 3139-52. 4. Polverelli N, Hernandez-Boluda JC, Czerw T, et al. Splenomegaly in patients with primary or secondary myelofibrosis who are candidates for allogeneic hematopoietic cell transplantation: a Position Paper on behalf of the Chronic Malignancies Working Party of the EBMT. Lancet Haematol 2023; 10(1): e59-e70. 5. Polverelli N, Mauff K, Kroger N, et al. Impact of spleen size and splenectomy on outcomes of allogeneic hematopoietic cell transplantation for myelofibrosis: A retrospective analysis by the chronic malignancies working party on behalf of European society for blood and marrow transplantation (EBMT). Am J Hematol 2021; 96(1): 69-79. 6. Hernandez-Boluda JC, Sheth V, Iacobelli S, et al. Impact of Donor Type on Outcomes After Allogeneic Hematopoietic Cell Transplantation in Myelofibrosis: A Study on Behalf of the Chronic Malignancies Working Party of the EBMT. Am J Hematol 2025. 7. Robin M, Iacobelli S, Koster L, et al. Treosulfan compared to busulfan in allogeneic haematopoietic stem cell transplantation for myelofibrosis: a registry-based study from the Chronic Malignancies Working Party of the EBMT. Bone marrow transplantation 2024; 59(7): 928-35. 8. Battipaglia G, Mauff K, Wendel L, et al. Thiotepa-busulfan-fludarabine (TBF) conditioning regimen in patients undergoing allogeneic hematopoietic cell transplantation for myelofibrosis: an outcome analysis from the Chronic Malignancies Working Party of the EBMT. Bone marrow transplantation 2021; 56(7): 1593-602. 9. McLornan DP, Hernandez-Boluda JC, Czerw T, et al. Allogeneic haematopoietic cell transplantation for myelofibrosis: proposed definitions and management strategies for graft failure, poor graft function and relapse: best practice recommendations of the EBMT Chronic Malignancies Working Party. Leukemia 2021; 35(9): 2445-59. 10. Polverelli N, Farina M, D'Adda M, et al. How We Manage Myelofibrosis Candidates for Allogeneic Stem Cell Transplantation. Cells 2022; 11(3).
Language: English
Subfield: Genetics
Field: Medicine
Open Access status: green
OpenAlex ID: W7093121779
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