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ACUTE MYELOID LEUKEMIA

Clinical evaluation of complete remission (CR) with partial hematologic recovery (CRh) in acute myeloid leukemia: a report of 7235 patients from seven cohorts

Leukemia volume 38, pages 389–392 (2024)Cite this article

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Response assessments provide key prognostic information and guide interpretation of trials testing novel therapies in acute myeloid leukemia (AML). Proposed originally in 1956 [1] and modified only minimally over time, morphologic complete remission (CR) continues to play a pivotal role in clinical trial design and analysis [2, 3]. Improved survival of patients achieving CR with intensive chemotherapy relative to those who fail to do so supports this importance [4,5,6].

Adequate recovery of neutrophils (≥1.0 × 109/L) and platelets (≥100 × 109/L) are key criteria for CR [3]. In the last 20 years, remission categories with less stringent criteria for blood count recovery have been introduced, including CR with incomplete platelet recovery (CRp; CR criteria met except platelets <100 × 109/L), CR with incomplete hematologic recovery (CRi; CR criteria met except either neutrophils < 1.0 × 109/L OR platelets <100 × 109/L) and, more recently, CR with partial hematologic recovery (CRh; CR criteria met except neutrophils ≥0.5 × 109/L AND platelets ≥50 × 109/L) [2, 3]. The latter has raised interest because of possible benefits related to reduced infections and freedom from platelet transfusion needs. However, while several studies have shown shorter survival with CRi than with CR [2, 6], the relative outcomes with CRh are unknown. This limitation is important because CRh is increasingly used as an endpoint in clinical trials. To address this limitation and begin to understand the role and value of CRh as a remission category, herein we: 1) provide the incidence of CRh among patients with AML treated with intensive therapies, and 2) characterize the association of CRh with overall survival relative to other remission categories.

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Fig. 1

Data availability

For original, de-identified data and/or computer code (R) for analyses please contact the corresponding author (mothus@fredhutch.org).

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Acknowledgements

Research reported in this publication was supported by grants U01-CA180888 and U01-CA180819 from the National Cancer Institute/National Institutes of Health (NCI/NIH), Bethesda, MD, USA. RBW acknowledges support from the José Carreras/E. Donnall Thomas Endowed Chair for Cancer Research. We acknowledge National Blood Cancer Registry data provided by the Australasian Leukemia and Lymphoma Group.

Author information

Author notes

  1. These authors contributed equally: Megan Othus, Elihu H. Estey, Roland B. Walter.

  2. Deceased: Elihu H. Estey.

Authors and Affiliations

  1. Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, USA

    Jacob S. Appelbaum & Hannah Hill

  2. Division of Hematology and Oncology, University of Washington, Seattle, WA, USA

    Jacob S. Appelbaum

  3. Seattle Children’s Therapeutics, Seattle Children’s Hospital, Seattle, WA, USA

    Jacob S. Appelbaum

  4. Department of Clinical Haematology, Peter MacCallum Cancer Centre, and Royal Melbourne Hospital, Melbourne, VIC, Australia

    Andrew H. Wei

  5. Division of Blood Cells and Blood Cancer, Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia

    Andrew H. Wei

  6. Department of Quantitative Health Sciences, Alliance Statistics and Data Management Center, Mayo Clinic, Rochester, MN, USA

    Sumithra J. Mandrekar

  7. Department of Pathology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia

    Ing S. Tiong

  8. The Malignant Haematology, Transplantation and Cellular Therapies Service, Alfred Hospital, Melbourne, VIC, Australia

    Ing S. Tiong, Chong Chyn Chua & Tse-Chieh Teh

  9. Australasia Leukaemia and Lymphoma Group (ALLG), Richmond, VIC, Australia

    Ing S. Tiong & Chong Chyn Chua

  10. Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia

    Chong Chyn Chua

  11. Department of Haematology, Northern Hospital, Melbourne, VIC, Australia

    Chong Chyn Chua

  12. Department of Haematology, Eastern Health, Box Hill, VIC, Australia

    Tse-Chieh Teh

  13. Austin Health, Melbourne, VIC, Australia

    Chun Yew Fong

  14. Eastern Health, Box Hill Hospital and Monash University, Melbourne, VIC, Australia

    Stephen B. Ting

  15. Department of Internal Medicine III, Ulm University Hospital, Ulm, Germany

    Daniela Weber & Konstanze Döhner

  16. Division of Biostatistics, German Cancer Research Center, Heidelberg, Germany

    Axel Benner

  17. Freelance Statistician, Saadati Solutions, Ladenburg, Germany

    Maral Saadati

  18. Department of Biostatistics and Bioinformatics, Moffitt Cancer Center, Tampa, FL, USA

    Jun Yin

  19. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA

    Richard M. Stone

  20. Department of Leukemia, MD Anderson Cancer Center, Houston, TX, USA

    Guillermo Garcia-Manero

  21. Duke University Cancer Center, Durham, NC, USA

    Harry P. Erba

  22. Washington University School of Medicine, St. Louis, MO, USA

    Geoffrey L. Uy

  23. City of Hope Comprehensive Cancer Center, Duarte, CA, USA

    Guido Marcucci

  24. University of Chicago, Chicago, IL, USA

    Richard A. Larson

  25. Centre for Trials Research, Cardiff University, Cardiff, UK

    Abin Thomas, Nuria Marquez Almuina & Ian Thomas

  26. Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK

    Sylvie D. Freeman

  27. School of Medicine, Nottingham University, Nottingham, UK

    Nigel H. Russel

  28. Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany

    Hartmut Döhner

  29. Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA

    Megan Othus

  30. Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA, USA

    Roland B. Walter

  31. Department of Medicine, Division of Hematology and Oncology, University of Washington, Seattle, WA, USA

    Roland B. Walter

  32. Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA

    Roland B. Walter

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  1. Jacob S. Appelbaum
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  14. Richard M. Stone
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  20. Abin Thomas
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  21. Sylvie D. Freeman
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  24. Ian Thomas
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  26. Hartmut Döhner
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  27. Megan Othus
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Contributions

EE and MO conceived the idea, analyzed the data, and wrote the manuscript. All other authors provided data, interpreted analyses, and wrote the manuscript.

Corresponding author

Correspondence to Megan Othus.

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Competing interests

MO: consulting fees from Merck and Biosights; Data Safety Monitoring Board Member for BMS, Glycomimetics, Grifols. HD: Advisory role for AbbVie, Agios, Amgen, Astellas, AstraZeneca, BERLIN-CHEMIE, Bristol Myers Squibb, Celgene, Gilead Sciences, Janssen, Jazz Pharmaceuticals, Novartis, Servier, Stemline, Syndax; research funding from AbbVie, Agios, Amgen, Astellas, Bristol Myers Squibb, Jazz Pharmaceuticals, Kronos-Bio, Novartis, Pfizer. RBW: laboratory research grants and/or clinical trial support from Aptevo, Celgene, ImmunoGen, Janssen, Jazz, Kite, Kura, and Pfizer; ownership interests in Amphivena; consultant to Abbvie, Adicet, Amphivena, BerGenBio, Bristol Myers Squibb, GlaxoSmithKline, ImmunoGen, Kura, and Orum. SJM: Consulting role: Flatiron Health; Harbinger Oncology, Inc; Leadership roles: NCI CTAC SCTWG, NCI SCTIC, Program Director for Alliance Statistics and Data Management Grant. RMS: Steering Committee: Abbvie; DSMC: Epizeyme, Takeda, Aptevo, Syntrix, ; Advisory board: BMS, CTI Biopharma, GSK, Hermavant, Ligand Pharma, Lava Therapeutics, Redona Therapeutics, Avencell, BerGen Bio, Cellularity, CTI Pharma, Kura Oncology, Rigel; Speaker, Actinium, Arog, Boston Pharmacueticals, Janssen, Syros: Curis Oncology, Dava Oncology, Jazz. CCC: Participation in advisory board meetings for AbbVie, Pfizer, Sumitomo Pharma Oncology; honoraria for speakers bureau for Bristol Myers Squibb, Astra Zeneca, AbbVie and Pfizer. AHW: has served on advisory boards for Novartis, Astra Zeneca, Astellas, GSK, Janssen, Jazz, Amgen, Roche, Pfizer, Abbvie, Servier, Gilead, BMS and Beigene; has consulted for Abbvie, Servier, Novartis, Shoreline, Aculeus, receives research funding to the Institution from Novartis, Abbvie, Servier, BMS, Janssen, Syndax, Astex, Astra Zeneca, Amgen; serves on speaker’s bureaus for Abbvie, Novartis, BMS, Servier, Astellas; AHW is an employee of the Walter and Eliza Hall Institute (WEHI). WEHI receives milestone and royalty payments related to the development of Venetoclax. Current and past employees of Walter and Eliza Hall Institute may be eligible for financial benefits related to these payments. AHW receives such a financial benefit. RAL: has acted as a consultant or advisor to AbbVie, Amgen, Ariad/Takeda, Astellas, Celgene/BMS, Curis, CVS/Caremark, Epizyme, Immunogen, Jazz Pharmaceuticals, Kling Biotherapeutics, MedPace, MorphoSys, Novartis, and Servier, and has received clinical research support to his institution from Astellas, Celgene, Cellectis, Daiichi Sankyo, Forty Seven/Gilead, Novartis, and Rafael Pharmaceuticals, and royalties from UpToDate. CYF: has received honoraria from Abbvie, Amgen, Beigene, Bristol-Myers Squibb, Jazz, Novartis, Pfizer and Servier; has acted as a consultant/advisor for Abbvie, Amgen, Astellas Pharma, Bristol-Myers Squibb, Jazz, Novartis, Pfizer and Servier; and has received research funding from Amgen, Astellas and Jazz. SDF: research funding from Jazz and BMS; Speakers Bureau with Jazz, Pfizer, and Novartis. NHR: Research Support and Advisory Role for Pfizer, Research Support from Jazz.

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Appelbaum, J.S., Wei, A.H., Mandrekar, S.J. et al. Clinical evaluation of complete remission (CR) with partial hematologic recovery (CRh) in acute myeloid leukemia: a report of 7235 patients from seven cohorts. Leukemia 38, 389–392 (2024). https://doi.org/10.1038/s41375-024-02143-8

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