Subsequent neoplasms and late mortality in children undergoing allogeneic transplantation for nonmalignant diseases

Justine M. Kahn, Ruta Brazauskas, Heather R. Tecca, Stephanie Bo-Subait, David Buchbinder, Minoo Battiwala, Mary E.D. Flowers, Bipin N. Savani, Rachel Phelan, Larisa Broglie, Allistair A. Abraham, Amy K. Keating, Andrew Daly, Baldeep Wirk, Biju George, Blanche P. Alter, Celalettin Ustun, Cesar O. Freytes, Amer M. Beitinjaneh, Christine DuncanEdward Copelan, Gerhard C. Hildebrandt, Hemant S. Murthy, Hillard M. Lazarus, Jeffery J. Auletta, Kasiani C. Myers, Kirsten M. Williams, Kristin M. Page, Lynda M. Vrooman, Maxim Norkin, Michael Byrne, Miguel Angel Diaz, Naynesh Kamani, Neel S. Bhatt, Andrew Rezvani, Nosha Farhadfar, Parinda A. Mehta, Peiman Hematti, Peter J. Shaw, Rammurti T. Kamble, Raquel Schears, Richard F. Olsson, Robert J. Hayashi, Robert Peter Gale, Samantha J. Mayo, Saurabh Chhabra, Seth J. Rotz, Sherif M. Badawy, Siddhartha Ganguly, Steven Pavletic, Taiga Nishihori, Tim Prestidge, Vaibhav Agrawal, William J. Hogan, Yoshihiro Inamoto, Bronwen E. Shaw, Prakash Satwani

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


We examined the risk of subsequent neoplasms (SNs) and late mortality in children and adolescents undergoing allogeneic hematopoietic cell transplantation (HCT) for nonmalignant diseases (NMDs). We included 6028 patients (median age, 6 years; interquartile range, 1-11; range,,1 to 20) from the Center for International Blood and Marrow Transplant Research (1995-2012) registry. Standardized mortality ratios (SMRs) in 2-year survivors and standardized incidence ratios (SIRs) were calculated to compare mortality and SN rates with expected rates in the general population. Median follow-up of survivors was 7.8 years. Diagnoses included severe aplastic anemia (SAA; 24%), Fanconi anemia (FA; 10%), other marrow failure (6%), hemoglobinopathy (15%), immunodeficiency (23%), and metabolic/ leukodystrophy syndrome (22%). Ten-year survival was 93% (95% confidence interval [95% CI], 92% to 94%; SMR, 4.2; 95% CI, 3.7-4.8). Seventy-one patients developed SNs (1.2%). Incidence was highest in FA (5.5%), SAA (1.1%), and other marrow failure syndromes (1.7%); for other NMDs, incidence was,1%. Hematologic (27%), oropharyngeal (25%), and skin cancers (13%) were most common. Leukemia risk was highest in the first 5 years posttransplantation; oropharyngeal, skin, liver, and thyroid tumors primarily occurred after 5 years. Despite a low number of SNs, patients had an 11-fold increased SN risk (SIR, 11; 95% CI, 8.9-13.9) compared with the general population. We report excellent long-term survival and low SN incidence in an international cohort of children undergoing HCT for NMDs. The risk of SN development was highest in patients with FA and marrow failure syndromes, highlighting the need for long-term posttransplantation surveillance in this population.

Original languageEnglish
Pages (from-to)2084-2094
Number of pages11
JournalBlood advances
Issue number9
StatePublished - May 12 2020

Bibliographical note

Funding Information:
Acknowledgments The Center for International Blood and Marrow Transplant Research is supported primarily by Public Health Service U24CA076518 from the National Institutes of Health (NIH), National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID); U24HL138660 from NIH, NHLBI and NCI; OT3HL147741, R21HL140314 and U01HL128568 from the NIH, NHLBI; HHSH250201700006C, SC1MC31881-01-00 and HHSH250201700007C from the Health Resources and Services Administration; and N00014-18-1-2850, N00014-18-1-2888, and N00014-20-1-2705 from the Office of Naval Research. Additional federal support is provided by NIH, NCI P01CA111412, R01CA152108, R01CA215134, R01CA218285, and R01CA231141; NIH, NHLBI R01HL126589, R01HL129472, R01HL130388, and R01HL131731; NIH, NIAID R01AI128775, U01AI069197, and U01AI126612; and Biomedical Advanced Research and Development Authority. Support is also provided by Be the Match Foundation, Boston Children’s Hospital, Dana-Farber, Japan Hematopoietic Cell Transplantation Data Center, St. Baldrick’s Foundation, the National Marrow Donor Program, the Medical College of Wisconsin, and from the following commercial entities: AbbVie; Actinium Pharmaceuticals, Inc.; Adaptive Biotechnologies; Adienne SA; Allovir, Inc.; Amgen, Inc.; Anthem, Inc.; Astellas Pharma US; AstraZeneca; Atara Biotherapeutics, Inc.; bluebird bio, Inc.; Bristol-Myers Squibb Co.; Celgene Corp.; Chimerix, Inc.; CSL Behring; CytoSen Therapeutics, Inc.; Daiichi Sankyo Co., Ltd.; Gamida-Cell, Ltd.; Genzyme; GlaxoSmithKline; HistoGenetics, Inc.; Incyte Corporation; Janssen Biotech, Inc.; Janssen Pharmaceuticals, Inc.; Janssen/Johnson & Johnson; Jazz Pharmaceuticals, Inc.; Kiadis Pharma; Kite Pharma; Kyowa Kirin; Legend Biotech; Magenta Therapeutics; Mallinckrodt LLC; Medac GmbH; Merck & Company, Inc.; Merck Sharp & Dohme Corp.; Mesoblast; Millennium, Takeda Oncology Co.; Miltenyi Biotec, Inc.; Novartis Oncology; Novartis Pharmaceuticals Corporation; Omeros Corporation; Oncoimmune, Inc.; Orca Biosystems, Inc.; Pfizer, Inc.; Phamacyclics, LLC; Regeneron Pharmaceuticals, Inc.; REGiM-MUNE Corp.; Sanofi Genzyme; Seattle Genetics; Sobi, Inc.; Takeda Oncology; Takeda Pharma; Terumo BCT; Viracor Eurofins; and Xenikos BV.

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© 2020 American Society of Hematology. All rights reserved.

ASJC Scopus subject areas

  • Hematology


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