Survival and Late Effects after Allogeneic Hematopoietic Cell Transplantation for Hematologic Malignancy at Less than Three Years of Age
Year: 2017
Type: article
Study design: Observational Study
Abstract: Very young children undergoing hematopoietic cell transplantation (HCT) are a unique and vulnerable population. We analyzed outcomes of 717 patients from 117 centers who survived relapse free for ≥1 year after allogeneic myeloablative HCT for hematologic malignancy at <3 years of age, between 1987 and 2012. The median follow-up was 8.3 years (range, 1.0 to 26.4 years); median age at follow-up was 9 years (range, 2 to 29 years). Ten-year overall and relapse-free survival were 87% (95% confidence interval [CI], 85% to 90%) and 84% (95% CI, 81% to 87%). Ten-year cumulative incidence of relapse was 11% (95% CI, 9% to 13%). Of 84 deaths, relapse was the leading cause (43%). Chronic graft-versus-host-disease 1 year after HCT was associated with increased risk of mortality (hazard ratio [HR], 2.1; 95% CI, 1.3 to 3.3; P = .0018). Thirty percent of patients experienced ≥1 organ toxicity/late effect >1 year after HCT. The most frequent late effects included growth hormone deficiency/growth disturbance (10-year cumulative incidence, 23%; 95% CI, 19% to 28%), cataracts (18%; 95% CI, 15% to 22%), hypothyroidism (13%; 95% CI, 10% to 16%), gonadal dysfunction/infertility requiring hormone replacement (3%; 95% CI, 2% to 5%), and stroke/seizure (3%; 95% CI, 2% to 5%). Subsequent malignancy was reported in 3.6%. In multivariable analysis, total body irradiation (TBI) was predictive of increased risk of cataracts (HR, 17.2; 95% CI, 7.4 to 39.8; P < .001), growth deficiency (HR, 3.5; 95% CI, 2.2 to 5.5; P < .001), and hypothyroidism (HR, 5.3; 95% CI, 3.0 to 9.4; P < .001). In summary, those who survived relapse free ≥1 year after HCT for hematologic malignancy at <3 years of age had favorable overall survival. Chronic graft-versus-host-disease and TBI were associated with adverse outcomes. Future efforts should focus on reducing the risk of relapse and late effects after HCT at early age.
Authors: Lynda M. Vrooman, Heather R. Millard, Ruta Brazauskas, Navneet S. Majhail, Minoo Battiwalla, Mary E. Flowers, Bipin N. Savani, Görgün Akpek, Mahmoud Aljurf, Rajinder Bajwa, K. Scott Baker, Amer Beitinjaneh, Menachem Bitan, David Buchbinder, Eric Chow, Christopher Dandoy, Andrew C. Dietz, Lisa Diller, Robert Peter Gale, Shahrukh K. Hashmi, Robert J. Hayashi, Peiman Hematti, Rammurti T. Kamble, Kimberly A. Kasow, Morris Kletzel, Hillard M. Lazarus, Adriana K. Malone, David I. Marks, Tracey A. O'Brien, Richard F. Olsson, Olle Ringden, Sachiko Seo, Amir Steinberg, Lolie C. Yu, Anne Warwick, Bronwen Shaw, Christine Duncan
Institutions: Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Medical College of Wisconsin, Cleveland Clinic, National Heart, Lung, and Blood Institute, National Heart, Lung, and Blood Institute Division of Intramural Research, Fred Hutch Cancer Center, Vanderbilt University Medical Center, Rush University Medical Center, King Faisal Specialist Hospital & Research Centre, Nationwide Children's Hospital, University of Miami, Tel Aviv Sourasky Medical Center, Children's Hospital of Orange County, Cincinnati Children's Hospital Medical Center, University of Southern California, Children's Hospital Los Angeles, Imperial College London, Mayo Clinic, Washington University in St. Louis, University of Wisconsin–Madison, UW Health University Hospital, Baylor College of Medicine, University of North Carolina at Chapel Hill, Lurie Children's Hospital, University Hospitals Cleveland Medical Center, University Hospitals Seidman Cancer Center, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, University Hospitals Bristol NHS Foundation Trust, Sydney Children's Hospital, Uppsala University, Karolinska Institutet, National Cancer Center Hospital East, Louisiana State University, University Medical Center New Orleans, Children's Hospital of New Orleans, Louisiana State University Health Sciences Center New Orleans, Uniformed Services University of the Health Sciences
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,650
Funders: National Marrow Donor Program, U.S. Department of Defense, U.S. Department of Health and Human Services, Roswell Park Cancer Institute, Be The Match Foundation, Amgen, Bristol-Myers Squibb, Pfizer, Astellas Pharma US, AstraZeneca, Genzyme, Merck, Sanofi, WellPoint, Leukemia and Lymphoma Society, Gilead Sciences, Fred Hutchinson Cancer Research Center, St. Baldrick's Foundation, Patient-Centered Outcomes Research Institute, Alexion Pharmaceuticals, Spectrum Pharmaceuticals, Celgene, HistoGenetics, University of Minnesota, Novartis Pharmaceuticals Corporation, Medical College of Wisconsin, Otsuka America Pharmaceutical, Seattle Genetics, Actinium Pharmaceuticals, Jazz Pharmaceuticals, Sunesis, Cerus Corporation, Atara Biotherapeutics, bluebird bio, Chimerix, Telomere Diagnostics, Janssen Scientific Affairs, Incyte, Miltenyi Biotec, MedImmune, Astellas Pharma, Otsuka Pharmaceutical, Medac, Health Resources and Services Administration, Genentech, Onyx Pharmaceuticals, U.S. Navy, Takeda Oncology, National Heart, Lung, and Blood Institute, Office of Naval Research, National Cancer Institute, National Institute of Allergy and Infectious Diseases, Gamida Cell
Awards: G1384772222, G1626132361, G1769371581, G2108949772, G2814340220, G3816434386, G3847019374, G4298420724, G4373273904, G4930744573, G5214925129, G6771248800, G6850693576, G777363952, G8122066879, G8649229721, G8872364087, G8876996369, A Data Resource for Blood and Marrow Transplants and Adoptive Cellular Therapy Research
OpenAlex ID: W2609492959