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Publications

Journal Article Ahead of print

PubMed: 41803403 DOI: 10.1038/s41375-026-02901-w

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

Leukemia

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

Affiliations

  • Groupe Francophone des Myélodysplasies, F-75010, Paris, France.
  • Université Paris Saclay, INSERM U1287, Gustave Roussy Cancer Center, Villejuif, France.
  • Service de Biostatistique et informatique médicale, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, F-75010, Paris, France.
  • Université Paris Cité, Institut de Recherche Saint-Louis UMR1342, INSERM, CNRS, F-75010, Paris, France.
  • Leukemia Institute Paris Saint-Louis, Paris, France.
  • MDS Unit, DMSC; AOU Careggi, University of Florence, Florence, Italy.
  • Fondazione Italiana Sindromi Mielodisplastiche (FISiM-ets), Bologna, Italy.
  • Hematology Department CHU Angers, Université Angers, Angers, France.
  • Service Hématologie Seniors, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, F-75010, Paris, France.
  • CNRS, Institut d'Histoire et Philosophie des Sciences et des Techniques, University Paris 1 Panthéon-Sorbonne, Paris, France.
  • Marien Hospital, Klinik für Hämatologie, Onkologie und klinische Immunologie, D-40479, Düsseldorf, Germany.
  • Deutsche MDS-Studiengruppe, D-04103, Leipzig, Germany.
  • Department of Hematology, Oncology and Stem Cell Transplantation, Faculty of Medicine - University Medical Center Freiburg, D-79106, Freiburg, Germany.
  • Service Hématologie Clinique adulte, CHU de Rennes, F-35000, Rennes, France.
  • Service d'Hématologie Oncologique et Thérapie Cellulaire, CIC INSERM 1402, University Hospital of Poitiers, Poitiers, France.
  • Heinrich-Heine University Düsseldorf, Universitätsklinik Düsseldorf, Klinik für Hämatologie, Onkologie und Klinische Immunologie, D-40225, Düsseldorf, Germany.
  • Hematology Unit, ASST Spedali Civili, I-25123, Brescia, Italy.
  • Université Grenoble Alpes, Hematology Department, CHU Grenoble Alpes, Grenoble, France.
  • University Hospital Halle, University Medicine Halle (Saale), D-06120, Halle (Saale), Germany.
  • Department of Hematology and Oncology, University Hospital Mannheim, Heidelberg University, Mannheim, Germany.
  • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico - ASST Fatebenefratelli-Sacco - University of Milan, Milan, Italy.
  • Service d'Hématologie, CHU Montpellier, Montpellier, France.
  • Hematology Unit, AOU «Maggiore della Carità » and University of Eastern Piedmont, I-28100, Novara, Italy.
  • Centre Henri Becquerel, F-76038, Rouen, France.
  • Technical University of Munich, Department of Medicine III, Munich, Germany.
  • Universitätsklinikum Carl Gustav Carus, Dresden, Germany.
  • Department of Hematology, Gustave Roussy Cancer Center, Villejuif, France.
  • Groupe Francophone des Myélodysplasies, F-75010, Paris, France.
  • Université Paris Cité, Institut de Recherche Saint-Louis UMR1342, INSERM, CNRS, F-75010, Paris, France.
  • Leukemia Institute Paris Saint-Louis, Paris, France.
  • Service Hématologie Adultes, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, F-75010, Paris, France.

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 9/L or WBC > 10 × 10 9/L at the 3- and 6-cycle evaluation respectively. After 6 cycles, persistence of monocytes > 1 × 10 9/L or WBC > 10 × 10 9/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 9/L AND iGRAN ≤ 0.40 ×10 9/L versus 15.3 months in others (p = 0.013). Biomarkers integrating blood counts and flow cytometry may predict CMML prognosis irrespective of treatment.

MeSH

Monocytes, Blood, Leukemia, Myelomonocytic, Chronic, Leukemia, Therapeutics, Prognosis