Does stringent cytoreduction improve survival in advanced proliferative chronic myelomonocytic leukemia?

Whether mitigation of myeloproliferation improves prognosis of CMML independently of bone marrow response is unknown. Flow-defined classical monocytes (cMo) and immature granulocytes (iGRAN) have not yet been studied as biomarkers of response. We inspected the prognostic value of WBC, circulating monocytes, cMo and iGRANs in the 120 DACOTA (NCT02214407) patients randomized to decitabine (n = 63) or hydroxyurea (n = 57) evaluated after 3 cycles with BM aspiration and complete blood count. Across arms, 59% and 56% patients had monocytes > 1 × 10<sup>9</sup>/L or WBC > 10 × 10<sup>9</sup>/L at the 3- and 6-cycle evaluation respectively. After 6 cycles, persistence of monocytes > 1 × 10<sup>9</sup>/L or WBC > 10 × 10<sup>9</sup>/L increased the hazard of death (HR = 5.38, p = 0.0003) irrespective of treatment, baseline CPSS and persistence of BM blast excess. After 3 cycles, both higher absolute cMo and iGRAN counts independently predicted poorer OS, without significant interaction with treatment arm. Median OS from landmark was 35.1 months in the 28% patients with cMo ≤ 0.94 ×10<sup>9</sup>/L AND iGRAN ≤ 0.40 ×10<sup>9</sup>/L versus 15.3 months in others (p = 0.013). Biomarkers integrating blood counts and flow cytometry may predict CMML prognosis irrespective of treatment.

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Journal
Leukemia
Published
2026-03-09
DOI
https://doi.org/10.1038/s41375-026-02901-w
Primary Topic
Acute Myeloid Leukemia Research
Type
article
Field-Weighted Citation Impact
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article

Does stringent cytoreduction improve survival in advanced proliferative chronic myelomonocytic leukemia?

Raphaël Itzykson, Stanislas Nimubona, Éric Solary, Anna Maria Pelizzari et al.
Leukemia
Acute Myeloid Leukemia Research
article

Does stringent cytoreduction improve survival in advanced proliferative chronic myelomonocytic leukemia?

Raphaël Itzykson, Stanislas Nimubona, Éric Solary, Anna Maria Pelizzari, Fatiha Chermat, Sophie Park, Lucie Laplane, Georgia Metzgeroth, Aristoteles Giagounidis, Rosa Sapena, Andrea Patriarca, Michael Lübbert, Francesco Onida, Katharina S. S. Götze, Margot Morabito, A. Stamatoullas, Nathalie Droin, Nadja Jaekel, Dorothée Selimoglu-Buet, Valeria Santini, Franciane Paul, Sylvie Chevret, Jose Miguel Torregrosa-Diaz, Sylvain Thépot, Pierre Fenaux, Ulrich Germing, Lionel Adès, Uwe Platzbecker
article en

Abstract

Whether mitigation of myeloproliferation improves prognosis of CMML independently of bone marrow response is unknown. Flow-defined classical monocytes (cMo) and immature granulocytes (iGRAN) have not yet been studied as biomarkers of response. We inspected the prognostic value of WBC, circulating monocytes, cMo and iGRANs in the 120 DACOTA (NCT02214407) patients randomized to decitabine (n = 63) or hydroxyurea (n = 57) evaluated after 3 cycles with BM aspiration and complete blood count. Across arms, 59% and 56% patients had monocytes > 1 × 10<sup>9</sup>/L or WBC > 10 × 10<sup>9</sup>/L at the 3- and 6-cycle evaluation respectively. After 6 cycles, persistence of monocytes > 1 × 10<sup>9</sup>/L or WBC > 10 × 10<sup>9</sup>/L increased the hazard of death (HR = 5.38, p = 0.0003) irrespective of treatment, baseline CPSS and persistence of BM blast excess. After 3 cycles, both higher absolute cMo and iGRAN counts independently predicted poorer OS, without significant interaction with treatment arm. Median OS from landmark was 35.1 months in the 28% patients with cMo ≤ 0.94 ×10<sup>9</sup>/L AND iGRAN ≤ 0.40 ×10<sup>9</sup>/L versus 15.3 months in others (p = 0.013). Biomarkers integrating blood counts and flow cytometry may predict CMML prognosis irrespective of treatment.

Leukemia
Centre National de la Recherche Scientifique (FR), Inserm (FR), Université Paris Cité (FR), Heidelberg University (DE), Université Paris-Saclay (FR), Centre Hospitalier Universitaire de Grenoble (FR), University Medical Center Freiburg (DE), Institut Gustave Roussy (FR), University Hospital Heidelberg (DE), Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (IT), Université de Poitiers (FR), Düsseldorf University Hospital (DE), Sorbonne Paris Cité (FR), Centre Hospitalier Universitaire de Montpellier (FR), Acute Leukemia French Association (FR), Assistance Publique – Hôpitaux de Paris (FR), Italian Foundation of Myelodysplastic Syndromes (IT), Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (IT), Centre Hospitalier Universitaire d'Angers (FR), CIC Rennes (FR), Marien Hospital Düsseldorf (DE), Groupe Francophone des Myélodysplasies (FR), Laboratoire National Henri Becquerel (FR), Institut Cochin (FR), Hôpital Saint-Louis (FR), University Hospital in Halle (DE), Centre Hospitalier Universitaire de Rennes (FR), Piedmont University (US), University Hospital Carl Gustav Carus (DE), Heinrich Heine University Düsseldorf (DE), University of Florence (IT), Université d'Angers (FR), Université Paris 1 Panthéon-Sorbonne (FR), Technical University of Munich (DE), Université Grenoble Alpes (FR), Leipzig University (DE)
Institut National de la Santé et de la Recherche Médicale, Centre National de la Recherche Scientifique, Institut Gustave-Roussy
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Openalex Percentile: Top 28%
Acute Myeloid Leukemia Research
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