Allogeneic Transplantation in the Rare Disease Myelodysplastic Syndrome/Myeloproliferative Neoplasm with Neutrophilia: Age and Disease Burden Determine Outcome

Abstract

Myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) with neutrophilia, as termed by the World Health Organization (WHO) in 2022 [1], formerly known as atypical chronic myeloid leukemia (aCML) [2], is a rare hematologic malignancy with a poor prognosis. Allogeneic hematopoietic stem cell transplantation (allo-HCT) is the only curative treatment, but prognostic factors for post-transplantation outcomes are poorly defined.

This retrospective multicenter analysis included 85 patients receiving allografts over a 30-year period at 8 German centers, representing the largest cohort reported at this writing. Univariable and multivariable analyses were performed to identify prognostic factors for post-transplantation outcome. Endpoints were overall survival (OS), relapse-free survival (RFS), cumulative incidence of relapse (CIR), and nonrelapse mortality (NRM). After a median follow-up of 7.6 years, 5-year OS, RFS, CIR, and NRM were 47%, 37%, 32%, and 29% respectively. Age ≥50 years and bone marrow (BM) blasts ≥5% were associated with inferior OS and RFS in univariable analyses, whereas a hemoglobin level of <8 g/dL adversely affected RFS. In our multivariable analysis, younger age remained an independent predictor for improved OS and RFS, whereas a higher Hb level was associated with superior RFS. Additionally, EZH2 and TET2 mutations were linked to increased relapse risk and inferior RFS, whereas TET2 mutations also negatively impacted OS. Although limited by its retrospective character, small sample size, and incomplete molecular data, this study shows that long-term survival after allo-HCT is achievable in patients with MDS/MPN with neutrophilia, particularly in younger individuals with low disease burden. However, relapse and NRM remain major challenges, underscoring the need for optimized post-transplantation strategies.