How We Manage Myelofibrosis Candidates for Allogeneic Stem Cell Transplantation

Abstract

Moving from indication to transplantation is a critical process in myelofibrosis. Most of guidelines specifically focus on either myelofibrosis disease or transplant procedure, and, currently, no distinct indication for the management of MF candidates to transplant is available. Nevertheless, this period of time is crucial for the transplant outcome because engraftment, non-relapse mortality, and relapse incidence are greatly dependent upon the pre-transplant management. Based on these premises, in this review, we will go through the path of identification of the MF patients suitable for a transplant, by using disease-specific prognostic scores, and the evaluation of eligibility for a transplant, based on performance, comorbidity, and other combined tools. Then, we will focus on the process of donor and conditioning regimens’ choice. The pre-transplant management of splenomegaly and constitutional symptoms, cytopenias, iron overload and transplant timing will be comprehensively discussed. The principal aim of this review is, therefore, to give a practical guidance for managing MF patients who are potential candidates for allo-HCT.

Management of Myelofibrosis during Treatment with Ruxolitinib: A Real-World Perspective in Case of Resistance and/or Intolerance

“…When considering the donor type, more than half of the physicians surveyed reported that, in the absence of an HLA-identical donor, they would use a haploidentical donor if the patient was indicated for transplantation, whereas 11% of physicians would only use a haploidentical donor in younger patients (<40 years) or in those with high-risk disease. Notably, increasing evidence has been reported in favor of haploidentical donors, with similar results to HLA-matched donors [ 22 , 27 ].…”

“…Approximately 50% of patients discontinue ruxolitinib within 3–5 years [ 9 ] and the advent of new agents and combination trials with ruxolitinib as a backbone complicate treatment choice. It should also be considered that not all available JAK2 inhibitors modify disease pathogenesis and that, as indicated in the literature, an enlarged spleen may reduce engraftment and increase the risk of non-relapse mortality [ 22 ].…”

“…On the one hand, splenectomy may have a disease-modifying effect considering that additional molecular and cytogenetical abnormalities may be present in the spleen compared with bone marrow; it may also reduce the risk of graft failure and relapse-risk mortality. Conversely, splenectomy is associated with increased mortality and morbidity, with possible thrombotic events and infections post-surgery [ 22 , 28 , 29 ].…”

Advances in management of primary myelofibrosis and polycythaemia vera: Implications in clinical practice

“…Nevertheless, it is best to not delay AHSCT to when disease progresses to avoid non‐engraftment and an increased risk of non‐relapse mortality (NRM). [35] Moreover, for patients progressing to the accelerated or blast phase of myelofibrosis, prognosis is poorer, as the probability of achieving long‐term disease control after transplant is severely reduced. Consequently, it is best to proceed to AHSCT as soon as possible.…”

“…fedratinib, momelotinib and pacritinib) should be considered when ruxolitinib treatment fails. [35] Fedratinib has been approved by both the EMA and the FDA for the treatment of disease‐related splenomegaly or symptoms in adults with PMF who are JAK inhibitor‐naïve or previously treated with ruxolitinib. [48]…”