Blood or marrow transplantation and cellular therapies in myeloproliferative neoplasms: A comprehensive review.

Philadelphia-negative myeloproliferative neoplasms (Ph-negative MPNs) are clonal malignancies, with a complex interaction of the malignant clone, extramedullary haematopoiesis, and chronic inflammation. In high-risk disease, transformation to blast phase remains a constant risk and outcomes are usually dismal. Allogeneic blood or marrow transplantation (BMT) remains the only potentially curative treatment to date. In this narrative review, we summarize the evidence available to date on the role of BMT in MPNs and the ongoing investigations exploring the use of mutant CALR-targeted immune-based therapies, including engineered cellular therapeutics. BMT aims at the eradication of the malignant clone, although not without risks. To balance the risk vs benefit, BMT is usually considered in patients with higher risk features of disease. Historically, matched related or unrelated donors were preferred, but with the emergence of post-transplantation cyclophosphamide (PTCy), mismatched, family or unrelated, donors are increasingly used. Reduced-intensity conditioning regimens and peripheral blood graft sources are commonly employed but can vary by individual patient and institutional practice. Post-transplantation monitoring remains critical because engraftment is often delayed, contributing to nonrelapse mortality. Molecular evidence of disease post-transplantation increases the risk of relapse, but optimal timing of monitoring and interventions thereafter remain elusive. We also review the BMT landscape in MDS/MPN overlap neoplasms. Prevention and effective management of relapse remains an unmet need in both MPN and MDS/MPN. The role of cellular therapies in MPN is investigational. Progress in target identification in CALR-mutated MPN has resulted in the development of Fc-silent antibodies, T cell redirecting antibodies, and engineered cellular therapies which are advancing in clinical development.