Chronic conditions, late mortality, and health status after childhood AML: a Childhood Cancer Survivor Study report

• Type of Material: Article
• Authors: Lucie M. Turcotte, University of Minnesota, Minneapolis; Jillian A. Whitton, Fred Hutchinson Cancer Research Center; Wendy M. Leisenring, Fred Hutchinson Cancer Research Center; Rebecca M. howell, University of Texas MD Anderson Cancer Center; Joseph P. Neglia, University of Minnesota, Minneapolis; Rachel Phelan, Medical College of Wisconsin; Kevin C. Oeffinger, Duke University; Kirsten K. Ness, St. Jude Children's Research Hospital; William G. Woods, Emory University; E. Anders Kolb, Nemours Children's Health System; Leslie L. Robison, St. Jude Children’s Research Hospital; Gregory T. Armstrong, St. Jude Children’s Research Hospital; Eric J. Chow, Fred Hutchinson Cancer Research Center
• Language: English
• Date: 2022-08-30
• Publisher: Elsevier
• Publication Version: Final Published Version
• Copyright Statement: © 2023 by The American Society of Hematology
• Final Published Version (URL): https://doi.org/10.1182/blood.2022016487
• Title of Journal or Parent Work: Blood
• Volume: 141
• Issue: 1
• Start Page: 90
• End Page: 101
• Grant/Funding Agency: Office of Naval Research; Public Health Service; National Institute of Allergy and Infectious Diseases; AbbVie; National Heart, Lung and Blood Institute; Medical College of Wisconsin; American Lebanese-Syrian Associated Charities; Health Resources and Services Administration; See information for a list of the rest of funding agencies.; National Cancer Institute; National Marrow Donor Program; NCI; Be the Match Foundation; Cancer Center Support
• Grant/Funding Information: This work was supported by the National Cancer Institute (NCI; CA55727, G.T.A., Principal Investigator; CA234232, L.M.T., Principal Investigator). Support to St. Jude Children’s Research Hospital was also provided by the Cancer Center Support (CORE) grant (CA21765, C. Roberts, Principal Investigator) and the American Lebanese-Syrian Associated Charities (ALSAC). The CIBMTR is supported primarily by Public Health Service U24CA076518 from the NCI, the National Heart, Lung and Blood Institute, and the National Institute of Allergy and Infectious Diseases; HHSH250201700006C from the Health Resources and Services Administration; and N00014 to 20-1-2832 and N00014 to 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 by the following commercial entities: AbbVie; Actinium Pharmaceuticals, Inc; Adaptive Biotechnologies Corporation; ADC Therapeutics; Adienne SA; Allogene; Allovir, Inc; Amgen, Inc; 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; Fate Therapeutics; 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; 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; Priothera; Sanofi; Sanofi-Aventis US Inc; Sobi, Inc; Stemcyte; Takeda Pharmaceuticals; Talaris Therapeutics; Terumo Blood and Cell Technologies; TG Therapeutics; Vertex Pharmaceuticals; and Xenikos BV.
• Keywords: childhood acute myeloid leukemia; AML survivors; Morbidity
• Subject - Topics: Leukemia; Pediatrics

Abstract

Five-year survival following childhood acute myeloid leukemia (AML) has increased following improvements in treatment and supportive care. Long-term health outcomes are unknown. To address this, cumulative incidence of late mortality and grades 3 to 5 chronic health condition (CHC) were estimated among 5-year AML survivors diagnosed between 1970 and 1999. Survivors were compared by treatment group (hematopoietic cell transplantation [HCT], chemotherapy with cranial radiation [chemo + CRT], chemotherapy only [chemo-only]), and diagnosis decade. Self-reported health status was compared across treatments, diagnosis decade, and with siblings. Among 856 survivors (median diagnosis age, 7.1 years; median age at last follow-up, 29.4 years), 20-year late mortality cumulative incidence was highest after HCT (13.9%; 95% confidence interval [CI], 10.0%-17.8%; chemo + CRT, 7.6%; 95% CI, 2.2%-13.1%; chemo-only, 5.1%; 95% CI, 2.8%-7.4%). Cumulative incidence of mortality for HCT survivors diagnosed in the 1990s (8.5%; 95% CI, 4.1%-12.8%) was lower vs those diagnosed in the 1970s (38.9%; 95% CI, 16.4%-61.4%). Most survivors did not experience any grade 3 to 5 CHC after 20 years (HCT, 45.8%; chemo + CRT, 23.7%; chemo-only, 27.0%). Furthermore, a temporal reduction in CHC cumulative incidence was seen after HCT (1970s, 76.1%; 1990s, 38.3%; P = .02), mirroring reduced use of total body irradiation. Self-reported health status was good to excellent for 88.2% of survivors; however, this was lower than that for siblings (94.8%; P < .0001). Although HCT is associated with greater long-term morbidity and mortality than chemotherapy-based treatment, gaps have narrowed, and all treatment groups report favorable health status.