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Management and Outcomes of Blast Transformed Chronic Myelomonocytic Leukemia

  • Myelodysplastic Syndromes and MPN/MDS Overlap (M Patnaik, Section Editor)
  • Published:
Current Hematologic Malignancy Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Despite recent advances in the treatment of de novo acute myeloid leukemia (AML), AML arising from antecedent chronic myelomonocytic leukemia (CMML) continues to have dismal outcomes. While the unique biological drivers of CMML and subsequent leukemic transformation (LT) have been revealed with advances in molecular characterization, this has not yet translated to the bedside. Here, we review these biologic drivers, outcomes with current therapies, and rationale avenues of future investigation specifically in blast phase CMML (CMML-BP).

Recent Findings

CMML-BP outcomes are studied as an aggregate with more common categories of AML with myelodysplasia-related changes (AML-MRCs) or the even broader category of secondary AML (sAML), which illustrates the crux of the problem. While a modest survival advantage with allogeneic hematopoietic stem cell transplant exists, the difficulty is bridging patients to transplant and managing patients that require an allograft-sparing approach. Limited data suggest that short-lived remissions can be obtained employing CPX-351 or venetoclax-based lower intensity combination therapy. Promising future strategies include repurposing cladribine, exploiting the supportive role of dendritic cell subsets with anti-CD123 therapies, MCL-1 inhibition, dual MEK/PLK1 inhibition, FLT3 inhibition in RAS-mutated and CBL-mutated subsets, and immune therapies targeting novel immune checkpoint molecules such as the leukocyte immunoglobulin-like receptor B4 (LILRB4), an immune-modulatory transmembrane protein restrictively expressed on monocytic cells.

Summary

The successful management of an entity as unique as CMML-BP will require a cooperative, concerted effort to design and conduct clinical trials dedicated to this rare form of sAML.

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  1. Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Danielle Hammond & Guillermo Montalban-Bravo

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  1. Danielle Hammond
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  2. Guillermo Montalban-Bravo
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Correspondence to Guillermo Montalban-Bravo.

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This article is part of the Topical Collection on Myelodysplastic Syndromes and MPN/MDS Overlap

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Hammond, D., Montalban-Bravo, G. Management and Outcomes of Blast Transformed Chronic Myelomonocytic Leukemia. Curr Hematol Malig Rep 16, 405–417 (2021). https://doi.org/10.1007/s11899-021-00643-3

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