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Acute myeloid leukemia

Management of hyperleukocytosis and impact of leukapheresis among patients with acute myeloid leukemia (AML) on short- and long-term clinical outcomes: a large, retrospective, multicenter, international study

Leukemia volume 34, pages 3149–3160 (2020)Cite this article

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Abstract

Hyperleukocytosis in acute myeloid leukemia (AML) is associated with inferior outcomes. There is limited high quality evidence to support the benefits of leukapheresis. We retrospectively collected data from patients with newly-diagnosed AML who presented with a white cell count (WBC) >50 × 109/L to 12 centers in the United States and Europe from 2006 to 2017 and received intensive chemotherapy. Logistic regression models estimated odds ratios for 30-day mortality and achievement of composite complete remission (CRc). Cox proportional hazard models estimated hazard ratios for overall survival (OS). Among 779 patients, clinical leukostasis was reported in 27%, and leukapheresis was used in 113 patients (15%). Thirty-day mortality was 16.7% (95% CI: 13.9–19.3%). Median OS was 12.6 months (95% CI: 11.5–14.9) among all patients, and 4.5 months (95% CI: 2.7–7.1) among those ≥65 years. Use of leukapheresis did not significantly impact 30-day mortality, achievement of CRc, or OS in multivariate analysis based on available data or in analysis based on multiple imputation. Among patients with investigator-adjudicated clinical leukostasis, there were statistically significant improvements in 30-day mortality and OS with leukapheresis in unadjusted analysis, but not in multivariate analysis. Given the significant resource use, cost, and potential complications of leukapheresis, randomized studies are needed to evaluate its value.

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Fig. 1: Overall survival.
Fig. 2: Forest plot of multivariable analysis.
Fig. 3: Forest plot of propensity score-matched multivariate analysis.

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Acknowledgements

AZ is a Leukemia and Lymphoma Society Scholar in Clinical Research and is also supported by a NCI’s Cancer Clinical Investigator Team Leadership Award (CCITLA). Research reported in this publication was in part supported by the National Cancer Institute of the National Institutes of Health under Award Number P30 CA016359. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. We would like to acknowledge all the patients who contributed data for this study, and the Frederick A. DeLuca Foundation for supporting the statistical analyses. MS is supported by the MSKCC Clinical Scholars T32 Program under award number 2T32 CA009512-31.

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Author notes

  1. These authors contributed equally: Maximilian Stahl, Rory M. Shallis, Wei Wei

Authors and Affiliations

  1. Department of Internal Medicine Section of Hematology, Yale School of Medicine, New Haven, CT, USA

    Maximilian Stahl, Rory M. Shallis, Nikolai A. Podoltsev, Jan Philipp Bewersdorf, Steven Gore & Amer M. Zeidan

  2. Department of Biostatistics, Yale School of Public Health, New Haven, CT, USA

    Wei Wei

  3. Hospital Universitario y Politecnico La Fe, Valencia, Spain; & CIBERONC, Instituto Carlos III, University of Valencia, Madrid, Spain

    Pau Montesinos, David Martínez-Cuadron, Rebeca Rodríguez-Veiga, Blanca Boluda, Florence Rabian, Evelyn Acuña-Cruz & Isabel Cano

  4. Hematology Department, Saint-Louis Hospital AP-HP, Paris, France

    Etienne Lengline, Emmanuel Raffoux, Raphaël Itzykson & Florence Rabian

  5. Department of Hematology, Oncology and Clinical Immunology, Heinrich-Heine-University Duesseldorf, Duesseldorf, Germany

    Judith Neukirchen & Ulrich Germing

  6. Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA

    Vijaya R. Bhatt

  7. Leukemia Program, Cleveland Clinic, Cleveland, OH, USA

    Mikkael A. Sekeres & Sudipto Mukherjee

  8. Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA

    Amir T. Fathi & Andrew M. Brunner

  9. Indiana University Simon Cancer Center, Indianapolis, IN, USA

    Heiko Konig & Adam Miller

  10. Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA

    Selina Luger, Christine M. McMahon & Brendan Yoo

  11. University of Illinois Cancer Center, Chicago, IL, USA

    Irum Khan, Ellen K. Ritchie & Emma Rabinovich

  12. Weill Cornell Medicine and The New York Presbyterian Hospital, New York, NY, USA

    Gail J. Roboz

  13. CHU of Nice, Hematology Department, Cote d’Azur University, Nice, France

    Thomas Cluzeau

  14. University of North Carolina Physician Network, Durham, NC, USA

    Jayadev Manikkam Umakanthan

  15. INCLIVA, University Clinical Hospital, Valencia, Spain

    Mar Tormo

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  1. Maximilian Stahl
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Contributions

Conception and design: MS, RS, WW, and AMZ. Provision of study materials or patients: all authors. Collection and assembly of data: all authors. Data analysis and interpretation: MS, RS, WW, and AMZ. Paper writing: all authors. Paper critical revision: all authors. Final approval of paper: all authors. Accountable for all aspects of the work: all authors.

Corresponding author

Correspondence to Amer M. Zeidan.

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Conflict of interest

MS: no relevant financial relationship(s) to disclose. RMS: no relevant financial relationship(s) to disclose. WW: no relevant financial relationship(s) to disclose. PM: Daiichi Sankyo: Consultancy and Speakers Bureau. Novartis: Research Funding and Speakers Bureau. EL: No relevant financial relationship(s) to disclose. JN: no relevant financial relationship(s) to disclose. VRB: consulting fees: CSL Behring, Agios, Abbvie, Partner therapeutics and Incyte. Research funding: Jazz, Incyte, Tolero Pharmaceuticals, Inc, and National Marrow Donor Program. MAS: no relevant financial relationship(s) to disclose. ATF: consulting/advisory board—Celgene, Takeda, Abbvie, Forty seven, NewLink, Trovagene, Pfizer, Daiichi Sankyo, Astellas, Amphivena. Clinical trial funding—Celgene and Agios. HK: no relevant financial relationship(s) to disclose. SL: no relevant financial relationship(s) to disclose. IK: Teva: Speakers Bureau. GJR: AbbVie: Consultancy. Amphivena Therapeutics: Consultancy. Argenx: Consultancy. Astex Pharmaceuticals: Consultancy. Bayer: Consultancy. Celgene Corporation: Consultancy. Celltrion: Consultancy. Daiichi Sankyo: Consultancy. Bayer: Consultancy. Eisai: Consultancy. Janssen Pharmaceuticals: Consultancy. Jazz Pharmaceuticals: Consultancy. Novartis: Consultancy. Daiichi Sankyo: Consultancy. Orsenix: Consultancy. Otsuka: Consultancy. Eisai: Consultancy. Pfizer: Consultancy. Roche/Genentech: Consultancy. Sandoz: Consultancy. Cellectis: Research Funding. Orsenix: Consultancy. TC: Celgene: Consultancy, Membership on an entity’s Board of Directors or advisory committees and Speakers. Bureau. Menarini: Consultancy. Jazz Pharma: Consultancy, Membership on an entity’s Board of Directors or advisory committees and Speakers Bureau. Amgen: Membership on an entity’s Board of Directors or advisory committees and Speakers Bureau. AbbVie: Membership on an entity’s Board of Directors or advisory committees and Speakers Bureau. Sanofi: Speakers Bureau. Pfizer: Speakers Bureau. DMC: no relevant financial relationship(s) to disclose. ER: no relevant financial relationship(s) to disclose. UG: Celgene: Honoraria, Research Funding and Consultancy. Novartis: Honoraria and Research Funding. Janssen: Honoraria. JMU: no relevant financial relationship(s) to disclose. SM: Aplastic Anemia & MDS International Foundation in Joint Partnership with Cleveland Clinic Taussig Cancer Institute: Honoraria. BioPharm Communications: Consultancy. Bristol Myers Squib: Honoraria and Speakers Bureau. LEK Consulting: Consultancy and Honoraria. Novartis: Consultancy, Membership on an entity’s Board of Directors or advisory committees and Research Funding. Pfizer: Honoraria. Projects in Knowledge: Honoraria. Takeda: Membership on an entity’s Board of Directors or advisory committees. AMB: Takeda: Research Funding. Celgene: Consultancy and Research Funding. Novartis: Research Funding. AMM: no relevant financial relationship(s) to disclose CMM: no relevant financial relationship(s) to disclose. EKR: Incyte: Consultancy and Speakers Bureau. Celgene: Consultancy, Other: Travel, Accommodations, Expenses and Speakers Bureau. Pfizer: Consultancy and Research Funding. Novartis: Consultancy, Other: Travel, Accommodations, Expenses, Research Funding and Speakers Bureau. ARIAD Pharmaceuticals: Speakers Bureau. Astellas Pharma: Research Funding. Bristol Myers Squibb: Research Funding. NS Pharma: Research Funding. RRV: no relevant financial relationship(s) to disclose. RI: no relevant financial relationship(s) to disclose. BB: No relevant financial relationship(s) to disclose. FR: no relevant financial relationship(s) to disclose. MT: no relevant financial relationship(s) to disclose. EGAC: no relevant financial relationship(s) to disclose. ER: no relevant financial relationship(s) to disclose. BY: no relevant financial relationship(s) to disclose. IC: no relevant financial relationship(s) to disclose. NAP: Agios Pharmaceuticals: Consultancy and Honoraria. Astellas Pharma: Research Funding. Blueprint Medicines: Consultancy and Honoraria. Incyte: Consultancy and Honoraria. Novartis: Consultancy and Honoraria. Boehringer-Ingelheim: Research Funding. Daiichi Sankyo: Research Funding. Sunesis Pharmaceuticals: Research Funding. Celator: Research Funding. Pfizer: Research Funding, Consultancy and Honoraria. Astex Pharmaceuticals: Research Funding. Celgene: Research Funding, Consultancy and Honoraria. Genentech: Research Funding. AI Therapeutics: Research Funding. Samus Therapeutics: Research Funding. Arog Pharmaceuticals: Research Funding. Kartos Therapeutics: Research Funding. JPB: no relevant financial relationship(s) to disclose. SDG: Celgene: Consultancy and Research Funding. AMZ received research funding from Celgene, Acceleron, Abbvie, Otsuka, Pfizer, Medimmune/AstraZeneca, Boehringer-Ingelheim, Trovagene, Incyte, Takeda, Novartis, Aprea, Astex, and ADC Therapeutics. AMZ had a consultancy with and received honoraria from AbbVie, Otsuka, Pfizer, Celgene, Jazz, Incyte, Agios, Boehringer-Ingelheim, Novartis, Acceleron, Astellas, Daiichi Sankyo, Cardinal Health, Seattle Genetics, BeyondSpring, Trovagene, Takeda, Ionis, and Epizyme. AMZ received travel support for meetings from Pfizer, Novartis, and Trovagene. None of these relationships were related to the development of this paper.

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Stahl, M., Shallis, R.M., Wei, W. et al. Management of hyperleukocytosis and impact of leukapheresis among patients with acute myeloid leukemia (AML) on short- and long-term clinical outcomes: a large, retrospective, multicenter, international study. Leukemia 34, 3149–3160 (2020). https://doi.org/10.1038/s41375-020-0783-3

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