# Allogeneic Transplant for CMML

## TL;DR

This paper reviews how allogeneic transplants and new strategies are improving treatment for a rare blood cancer called CMML.

## Contribution

The paper highlights novel approaches to individualized transplant timing and new therapies that may improve outcomes in CMML.

## Key findings

- Individualized transplant timing improves life expectancy in CMML patients.
- Treosulfan-based and thiotepa-busulfan regimens show favorable toxicity and relapse profiles.
- Personalized approaches integrating genetic risk and disease characteristics enhance transplant strategies.

## Abstract

Chronic myelomonocytic leukemia (CMML) is a rare hematologic malignancy at the intersection of myelodysplastic (MDS) and myeloproliferative neoplasms, predominantly affecting older adults. Allogeneic hematopoietic cell transplantation (allo-HCT) remains the only curative option, yet its application is limited by the advanced age and comorbidities of most patients. Recent classification updates and refined prognostic tools, particularly molecularly integrated models like CPSS-Mol have enhanced patient stratification and informed transplant timing. The aim of this review is to highlight the evolving landscape of CMML management, with a focus on the role of allo-HCT.

Novel studies patients demonstrated that individualized transplant timing significantly improved life expectancy. Optimizing transplant outcomes hinges on several factors:managing pretransplant splenomegaly, choosing appropriate debulking strategies, selecting optimal donors, and tailoring conditioning regimens. New data favor treosulfan-based and thiotepa-busulfan regimens for their favorable toxicity and relapse profiles. Post-transplant, strategies like post-transplant cyclophosphamide (PTCy) for GVHD prophylaxis and emerging approaches to minimal residual disease (MRD) monitoring offer additional refinements in patient management. While no MRD studies are CMML-specific, extrapolation from MDS supports its role in relapse prediction. Innovative therapies, including hypomethylating agent combinations, venetoclax, targeted inhibitors, and immunotherapies are under active investigation, with potential to improve pre- and post-transplant outcomes.

Advancements in molecular classification, dynamic prognostic tools, and therapeutic strategies are reshaping the CMML treatment paradigm. Personalized approaches that integrate genetic risk, patient fitness, and disease characteristics are enabling more effective transplant strategies, with the ultimate goal of extending survival and improving quality of life in this complex and historically difficult-to-treat malignancy.