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Fedratinib as an alternative to splenectomy for refractory splenomegaly prior to transplant for myelofibrosis

Bone Marrow Transplantation volume 60, pages 237–240 (2025)Cite this article

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Myelofibrosis (MF), either primary (PMF) or following essential thrombocythemia (ET) or polycythemia vera (PV), is associated with morbidity and mortality from dysregulated cytokines, cytopenias, symptomatic splenomegaly, and progression to blast-phase (BP). The only curative therapy for MF is allogeneic haematopoietic stem cell transplant (HCT) which is recommended for patients with higher-risk disease with good performance status and an available donor. Prior studies observed that half of patients with an indication for HCT prefer to delay in favor symptom-directed JAK inhibitor (JAKi) therapy [1, 2]. While JAKi therapy has been effective in ameliorating constitutional symptoms and splenomegaly, duration of benefit is limited, with most patients experiencing failure by 2-3 years and subsequent poor outcomes. In patients with JAKi therapy failure HCT is recommended by several expert guidelines and recommendations [3]. A study from Princess Margaret observed improved long-term survival with HCT compared to other best available treatment in patients with first-line JAKi therapy failure [4].

JAKi therapy failure is commonly due to sub-optimal/loss of spleen response which can impact success of HCT as patients with splenomegaly have increased risk of poor graft function, graft failure, and disease relapse [5]. A recent position paper from the European Society for Blood and Marrow Transplantation (EBMT), have recommended intervention to improve splenomegaly in patients with spleen length >15 cm palpable or >22 cm by radiographic measurements [5]. Surgical splenectomy is the definitive option recommended but is associated with complications that can jeopardize a patient’s fitness to undergo HCT. EBMT recommendations highlight the unmet need for more systematic data on use of second-line JAKi prior to HCT [3].

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

This work was supported by program project grant from and the Elizabeth and Tony Comper Foundation to the MPN Program (VG). VG is supported by Barbara Baker chair in Leukemia and related disorders.

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Authors and Affiliations

  1. Medical Oncology & Hematology, Sunnybrook Health Sciences Centre, Toronto, ON, Canada

    James T. England

  2. Medical Oncology & Hematology, Princess Margaret Cancer Centre, Toronto, ON, Canada

    Taylor Nye, Verna Cheung, Auro Viswabandya, Hassan Sibai & Vikas Gupta

  3. Department of Surgery, Women’s College Hospital, Toronto, ON, Canada

    David R. Urbach

Authors
  1. James T. England
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  2. Taylor Nye
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  3. Verna Cheung
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  4. David R. Urbach
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  5. Auro Viswabandya
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  6. Hassan Sibai
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  7. Vikas Gupta
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Contributions

JTE, TN, VC, DRU, AV, HS, and VG contributed to clinical patient management; JE, TN, and VC collected the clinical data; JTE performed statistical analysis, JTE and VG wrote the manuscript; VG designed and supervised the study and was overall responsible for the conduct of the study. All authors reviewed the manuscript and affirmed for publication.

Corresponding author

Correspondence to Vikas Gupta.

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Competing interests

JTE, TN, VC, DRU and AV report no conflicts or competing interests to declare. HS has received Honoraria for Consulting or Advisory Role for Novartis, BMS, Gilead Sciences, AbbVie, Jazz, Pfizer. VG has received research funding through his institution and honoraria from Novartis, Abb Vie and and has served on the advisory board of Novartis, Incyte, GSK, BMS-Celgene, Abb Vie, Sierra Oncology, Pfizer and Daichii Sankyo.

Ethics approval and consent to participate

This study has been conducted in accordance with the Tri-Council Policy Statement (TCSP-2) for ethical conduct for research involving humans, and was approved by the University Health Network research ethics board (#21-5954). Written informed consent was obtained from all study subjects.

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England, J.T., Nye, T., Cheung, V. et al. Fedratinib as an alternative to splenectomy for refractory splenomegaly prior to transplant for myelofibrosis. Bone Marrow Transplant 60, 237–240 (2025). https://doi.org/10.1038/s41409-024-02464-3

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