Abstract
We investigated the impact of the number of induction/consolidation cycles on outcomes of 3113 adult AML patients who received allogeneic hematopoietic cell transplantation (allo-HCT) between 2008 and 2019. Patients received allo-HCT using myeloablative (MAC) or reduced-intensity (RIC) conditioning in first complete remission (CR) or with primary induction failure (PIF). Patients who received MAC allo-HCT in CR after 1 induction cycle had 1.3-fold better overall survival (OS) than 2 cycles to CR and 1.47-fold better than ≥3 cycles. OS after CR in 2 or ≥3 cycles was similar. Relapse risk was 1.65-fold greater in patients receiving ≥3 cycles to achieve CR. After RIC allo-HCT, the number of induction cycles to CR did not affect OS. Compared to CR in 1 cycle, relapse risk was 1.24-1.41-fold greater in patients receiving 2 or ≥3 cycles. For patients receiving only 1 cycle to CR, consolidation therapy prior to MAC allo-HCT was associated with improved OS vs. no consolidation therapy. Detectable MRD at the time of MAC allo-HCT did not impact outcomes while detectable MRD preceding RIC allo-HCT was associated with an increased risk of relapse. For allo-HCT in PIF, OS was significantly worse than allo-HCT in CR after 1–3 cycles.
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Data availability
The final analysis dataset will be posted to the CIBMTR website at https://www.cibmtr.org/ReferenceCenter/PubList/PubDsDownload/Pages/default.aspx. CIBMTR supports accessibility of research in accord with the National Institutes of Health (NIH) Data Sharing Policy and the National Cancer Institute (NCI) Cancer Moonshot Public Access and Data Sharing Policy. The CIBMTR only releases de-identified datasets that comply with all relevant global regulations regarding privacy and confidentiality.
Change history
22 March 2023
A Correction to this paper has been published: https://doi.org/10.1038/s41375-023-01814-2
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Acknowledgements
The authors thank the patients and families for their courage and confidence in their medical teams; and the data management staff at the transplant Centers for their dedicated work in submitting data to the CIBMTR. This work was supported in part by the Intramural Research Program of the National Heart, Lung, and Blood Institute (CSH).
Funding
The CIBMTR is supported primarily by Public Health Service U24CA076518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID); HHSH250201700006C from the Health Resources and Services Administration (HRSA); and N00014-20-1-2832 and N00014-21-1-2954 from the Office of Naval Research; support is also provided by Be the Match Foundation, the Medical College of Wisconsin, the National Marrow Donor Program, and from the following commercial entities: AbbVie; Actinium Pharmaceuticals, Inc.; Adaptimmune; Adaptive Biotechnologies Corporation; ADC Therapeutics; Adienne SA; Allogene; Allovir, Inc.; Amgen, Inc.; Angiocrine; Anthem; Astellas Pharma US; AstraZeneca; Atara Biotherapeutics; BeiGene; bluebird bio, inc.; Bristol Myers Squibb Co.; CareDx Inc.; CRISPR; CSL Behring; CytoSen Therapeutics, Inc.; Eurofins Viracor, DBA Eurofins Transplant Diagnostics; Gamida Cell, Ltd.; Gilead; GlaxoSmithKline; HistoGenetics; Incyte Corporation; Iovance; Janssen Research & Development, LLC; Janssen/Johnson & Johnson; Jasper Therapeutics; Jazz Pharmaceuticals, Inc.; Kadmon, a Sanofi Company; Karius; Kiadis Pharma; Kite, a Gilead Company; Kyowa Kirin; Legend Biotech; Magenta Therapeutics; Mallinckrodt Pharmaceuticals; Medac GmbH; Medexus Pharma; Merck & Co.; Mesoblast; Millennium, the Takeda Oncology Co.; Miltenyi Biotec, Inc.; MorphoSys; Novartis Pharmaceuticals Corporation; Omeros Corporation; OptumHealth; Orca Biosystems, Inc.; Ossium Health, Inc.; Pfizer, Inc.; Pharmacyclics, LLC, An AbbVie Company; Pluristem; PPD Development, LP; Sanofi; Sobi, Inc.; Stemcyte; Takeda Pharmaceuticals; Talaris Therapeutics; Terumo Blood and Cell Technologies; TG Therapeutics; Vertex Pharmaceuticals; Vor Biopharma Inc.; Xenikos BV.
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The study was proposed by MB, revised by MB and DJW, statistical analysis by KC and M-JZ. All authors reviewed the analysis, revised the manuscript and approved the final submission. Additional contributing co-authors from the Writing Committee: A. Samer Al-Homsi, Hassan B. Alkhateeb, Yasuyuki Arai, Jean-Yves Cahn, Moussab Damlaj, Firas El Chaer, Jong Wook Lee, Hongtao Liu, Leland Metheny, Fotios V. Michelis, Pashna Munshi, Alberto Mussetti, David Rizzieri, Sachiko Seo, Leo F. Verdonck.
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MB reports employment with Genentech. TB reports Mayo Clinic Comprehensive Cancer Center Developmental Fund to conduct research P30 CA015083; and honoraria with Pfizer hematology and Oncology. MB reports research support for unrelated project paid to Novartis. NB served as a consultant or had an advisory role with Medexus Pharmaceuticals, Magenta Therapeutics, CareDx Pharma, Sanofi and CTI BioPharma. VB reports institutional grants or contracts from Abbvie, Pfizer, Incyte, Jazz, Tolero Pharmaceuticals, Inc., and National Marrow Donor Program; consulting fees to self from Genentech, Rigel, Agios, Incyte, Servier Pharmaceuticals LLC, Omeros, Takeda, Partnership for health analytic research, LLC (which in turn, receives funds from Jazz Pharmaceuticals) and Abbvie; safety monitoring committee member for Protagonist; and drug support (institutional) for a trial from Chimerix. VB reports as member of the American Board of Pediatrics Pediatric Hematology/Oncology subboard; National Leader of Pediatric and AYA oncology disease section with Caris Precision Oncology Alliance. JC reports as a member Data Safety Monitoring Board with Allovir, consulting fees with advisory board membership with Jazz Pharmaceuticals, Pfizer, and Amgen; and stocks with Actinium Pharmaceuticals, Bluebird Bio/2Seventy, Dynavax Technologies, aTyr Pharma, Gamida Cell, Miragen Therapeutics, Mustang Bio, Novavax, Ovid Therapeutics, Sorrento Therapeutics, TG Therapeutics, Vaxart, and Veru. RPG reports consulting fees with Ascentage Pharma Group, BeiGene Ltd., Kite Pharma, Inc., Fusion Pharma LLC, LaJolla NanoMedical, Inc., Mingsight Pharma, Inc., Prolacta Bioscience, Inc., CStone Pharmaceuticals. Board participation on FFF Enterprises, Azca, Inc., RakFond Foundation, Antegene Biotech LLC, Stem Rad LTD; and stock or stock options with Bristol Myers. SG reports participation on advisory board with Astellas, Daiichi Sankyo, Bristol Myers Squibb, Sanofi Aventis, AstraZeneca, and Kite Pharma. MRGr reports consulting fees and/or advisory board with Abbvie, Agios/Servier, Amgen, Astellas, Blueprint Medicines, Bristol Myers Squibb, Cardinal Health, CTI Biopharma, Daiichi Sankyo, Gamida Cell, Gilead, Incyte, Invitae, Karius, Novartis, Ono Pharmaceutical, Pfizer, Pharmacosmos, Premier, Sierra Oncology, and Stemline; stock ownership in Medtronic; medical writing with Incyte, Amgen, Jazz, Janssen, Genentech/Roche; and support with Incyte, Genetech/Roche, Janssen. Shahrukh Hashmi reports honorarium for educational talks (all non-promotional, majority on “quality of life” or “survivorship”) in CME accredited educational seminars/conferences. This is over the past 10 years: Pfizer, Novartis, Gilead, Sanofi, Therakos, Janssen, MSD; Relationships: No financial but only volunteer: ASTCT, WBMT, CIBMTR. GH reports grants or contracts from Incyte, Acerta/Astra Zeneca, Takeda, Jazz Pharmaceuticals, and Pharmacyclics; consulting fees from Incyte, Morphosys, Alexio n Pharmaceutcials, Karyopharm, Seattle Genetics, Janssen; participation on a Data Safety Monitoring Board or Advisory Board with Rapa Therapauetics, serves as Vice President, Kentucky Society for Clinical Oncology; Axim Biotechnologies, GW Pharmaceuticals, Cardinal Health, Clovis Oncology, Pfizer, Cellectis, CVS Health, Bluebird Bio, Biogen, Charlottes Webb, AImmune Therapeutics Inc, Medical PPTYS TR Inc, Caretrust Reit Inc, Moderna Therapeutics, Zoom. MK-D reports consulting fees with Darrchi Sankyo. HML reports honoraria for consulting fees from Jazz Pharmaceuticals, CSL Behring, Partner Therapeutics, Actinium, Pluristem, Seattle Genetics; payment or honoraria from speakers’ bureau with Jazz Pharmaceuticals, Seattle Genetics, AstraZeneca; travel reimbursement from Jazz Pharmaceuticals and Seattle Genetics; honoraria for participation on a Data Safety Monitoring Board or Advisory Board with BMS-Celgene and Biosight; and stock options with Partner Therapeutics. DM reports honoraria for AstraZeneca; advisory board for Morphosys and Seagen; and research funding with Genentech, ADC therapeutics, and Karyopharm. AS is the St. Jude Children’s Research Hospital site principal investigator of clinical trials sponsored by Vertex Pharmaceuticals/CRISPR Therapeutics (NCT03745287) and by Novartis (NCT04443907). The industry sponsors provide funding for the clinical trial, which includes salary support paid to AS’s institution. AS has received consultant fee from Spotlight Therapeutics, Medexus Inc. and Vertex Pharmaceuticals. He has also received research funding from CRISPR Therapeutics and honoraria from Vindico Medical Education. None of these are related to the work presented in this manuscript. Kirsten Williams reports grants for immunotherapy in AML unrelated to current project with Leukemia Lymphoma Society; payment for educational seminar in lung complications of HCT with ASH; ASTCT board of directors meeting; ASH for educational seminar; patents pending for MRD test for AML and ALL unrelated to this work; and leadership roles with ASTCT, CIBMTR, and PTCTC. CH reports the National Heart, Lung, and Blood Institute receives research funding for the laboratory of Dr Hourigan from Sellas; and the National Heart, Lung, and Blood Institute receives research funding for the laboratory of Dr Hourigan from the Foundation of the NIH AML MRD Biomarkers Consortium. PK reports participation on advisory board with Kite, Pfizer, and Jazz. Marcos de Lima reports research agreements (no direct payments) with Miltenyi Biotec; payment to Pfizer; and consulting fees from BMS/Pfizer/Incyte.
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Boyiadzis, M., Zhang, MJ., Chen, K. et al. Impact of pre-transplant induction and consolidation cycles on AML allogeneic transplant outcomes: a CIBMTR analysis in 3113 AML patients. Leukemia 37, 1006–1017 (2023). https://doi.org/10.1038/s41375-022-01738-3
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DOI: https://doi.org/10.1038/s41375-022-01738-3
