Year: 2019
Type: article
Study design: Observational Study
Abstract: Importance: Studies demonstrating improved survival after allogeneic hematopoietic cell transplant generally exclude infants. Objective: To analyze overall survival trends and other outcomes among infants who undergo allogeneic hematopoietic cell transplant. Design, Setting, and Participants: In this cohort study, we used time-trend analysis to evaluate 3 periods: 2000 through 2004, 2005 through 2009, and 2010 through 2014. The study was conducted in a multicenter setting through the Center for International Blood and Marrow Transplant Research, which is made up of a voluntary working group of more than 450 transplant centers worldwide. Two groups of infants aged 1 year or younger in 2 cohorts were included: those with malignant conditions, such as leukemia, and those with nonmalignant disorders, including immunodeficiencies. Data analysis was conducted from July 2017 to December 2018. Exposures: Allogeneic hematopoietic cell transplant. Main Outcomes and Measures: Survival trends, disease relapse, and toxicity. Results: A total of 2498 infants with a median age of 7 months (range, <1-12 months) were included. In the nonmalignant cohort (n = 472), survival rates improved from the first to the second period (hazard ratio, 0.77 [95% CI, 0.63-0.93]; P = .007) but did not change after 2004. Compared with infants with nonmalignant diseases (n = 2026; 3-year overall survival: 2000-2004, 375/577 [65.0%]; 2005-2009, 503/699 [72.0%]; and 2010-2014, 555/750 [74.0%]), those with malignant conditions had poorer survival rates, without improvement over time (3-year overall survival: 2000-2004, 109/199 [54.8%]; 2005-2009, 104/161 [64.6%]; and 2010-2014, 66/112 [58.9%]). From 2000 through 2014, relapse rates increased in infants with malignant conditions (3-year relapse rate: 2000-2004, 19% [95% CI, 14%-25%]; 2005-2009, 23% [95% CI, 17%-30%]; 2010-2014, 36% [95% CI, 27%-46%]; P = .01). Sinusoidal obstruction syndrome was frequent, occurring with a cumulative incidence of 13% (95% CI, 11%-16%) of infants with nonmalignant diseases and 32% (95% CI, 22%-42%) of those with malignant diseases. Generally, recipients of human leukocyte antigen-identical sibling bone marrow grafts had the best outcomes. Conclusions and Relevance: Survival rates have not improved for infants with malignant diseases over the 15-year study period. Infants with nonmalignant diseases had improved survival rates in the earlier but not the later study period. Higher relapses for the malignant cohort and toxicities for all infants remain significant challenges. Strategies to reduce relapse and toxicity and optimize donor and graft selection may improve outcomes in the future.
Authors: Suhag H. Parikh, Prakash Satwani, Kwang Woo Ahn, Natasha A. Sahr, Caitrin Fretham, Allistair A. Abraham, Vaibhav Agrawal, Jeffery J. Auletta, Hisham Abdel-Azim, Edward Copelan, Miguel-Angel Diaz, Christopher C. Dvorak, Haydar A. Frangoul, Cesar O. Freytes, Shahinaz M. Gadalla, Robert Peter Gale, Biju George, Usama Gergis, Shahrukh Hashmi, Peiman Hematti, Gerhard C. Hildebrandt, Amy K. Keating, Hillard M. Lazarus, Kasiani C. Myers, Richard F. Olsson, Timothy Prestidge, Seth J. Rotz, Bipin N. Savani, Evan B. Shereck, Kirsten M. Williams, Baldeep Wirk, Marcelo C. Pasquini, Alison W. Loren
Institutions: Duke University, Duke Medical Center, Columbia University Irving Medical Center, Medical College of Wisconsin, St. Jude Children's Research Hospital, National Marrow Donor Program, Children's National, Center for Cancer and Blood Disorders, Indiana University Indianapolis, Nationwide Children's Hospital, Children's Hospital Los Angeles, Carolinas Healthcare System, Levine Cancer Institute, Hospital Infantil Universitario Niño Jesús, University of California, San Francisco, UCSF Benioff Children's Hospital, Centennial Medical Center, Children’s Hospital at TriStar Centennial, National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics, Imperial College London, Christian Medical College, Vellore, NewYork–Presbyterian Hospital, Weill Cornell Medical Center, King Faisal Specialist Hospital & Research Centre, University of Wisconsin–Madison, UW Health University Hospital, University of Kentucky HealthCare, Markey Cancer Center, Children's Hospital Colorado, University of Colorado Denver, Case Western Reserve University, Cincinnati Children's Hospital Medical Center, University of Cincinnati, University of Cincinnati Medical Center, Karolinska Institutet, Starship Children's Health, Cleveland Clinic, Vanderbilt University, Roger Williams Medical Center, Oregon Health & Science University, Seattle Cancer Care Alliance, University of Pennsylvania
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: U.S. Department of Defense, Vanderbilt University, University of Pennsylvania, Cincinnati Children's Hospital Medical Center, Children's Hospital Colorado, Cleveland Clinic, University of Cincinnati, Case Western Reserve University, Imperial College London, King Faisal Specialist Hospital and Research Centre, Karolinska Institutet, Christian Medical College, Vellore, National Institutes of Health, Health Resources and Services Administration, Weill Cornell Medical College, Perelman School of Medicine, University of Pennsylvania, U.S. Navy, College of Medicine, University of Cincinnati, National Heart, Lung, and Blood Institute, Office of Naval Research, National Cancer Institute, National Institute of Allergy and Infectious Diseases
Awards: G1204469256, G1769371581, G1770367129, G1889018580, G1897206528, G2459474397, G28020125, G2814340220, G3639700628, G4298420724, G439395074, G4504108201, G4930744573, G5580148221, G5733286835, G6371648221, G6463748905, G6743874442, G7335140382, G7558041529, Blood & Marrow Transplant Clinical Trials Network Data Coordinating Center, G851645379, G8876996369, A Data Resource for Blood and Marrow Transplants and Adoptive Cellular Therapy Research, Cancer Center Support Grant (CCSG)
OpenAlex ID: W2922232534