Prognostic impact and timing considerations for allogeneic hematopoietic stem cell transplantation in chronic myelomonocytic leukemia

Chronic myelomonocytic leukemia (CMML) is a clonal disorder of aging hematopoietic stem cells characterized by overlapping features of myeloproliferation and myelodysplasia 1 , with a median overall survival (OS) of ≤36 months 1 , 2 . Hypomethylating agents (HMAs) have an overall response rate of about 30–40%; however, these agents are ineffective in altering the natural disease biology due to inability to prevent acquisition of molecular abnormalities and transformation to acute myeloid leukemia (AML) 3 . Allogeneic hematopoietic stem cell transplantation (alloHCT) is a potentially curative option, with 20–50% patients achieving long-term remissions. However, as the median age of presentation is 73 years, only a fraction (<20%) of CMML patients are eligible for alloHCT 4 . Prognostic models such as the Mayo Prognostic Model (MPM), Mayo Molecular Model (MMM), Groupe Francais des Myelodysplasies, and the CMML-specific prognostic scoring system (CPSS) are important tools to identify patients at high risk for disease progression and death 5 , 6 , 7 , 8 , 9 . Several retrospective analyses of outcomes in alloHCT patients have identified adverse cytogenetics, blast percentage, HCT-comorbidity Index, time to alloHCT, disease control at the time of alloHCT and acute and chronic graft vs. host disease (GVHD) as factors influencing OS and AML-free survival (LFS) 10 , 11 , 12 , 14 , 15 .