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Original Investigation
March 18, 2019

Survival Trends in Infants Undergoing Allogeneic Hematopoietic Cell Transplant

Author Affiliations
  • 1Department of Pediatric Blood and Marrow Transplant, Duke University Medical Center, Durham, North Carolina
  • 2Division of Pediatric Hematology, Oncology and Stem Cell Transplantation, Department of Pediatrics, Columbia University Medical Center, New York, New York
  • 3Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee
  • 4St Jude Children’s Research Hospital, Memphis, Tennessee
  • 5Center for International Blood and Marrow Transplant Program, National Marrow Donor Program/Be the Match, Minneapolis, Minnesota
  • 6Division of Blood and Marrow Transplantation, Center for Cancer and Blood Disorders, Children’s National Health System, Washington, DC
  • 7Indiana University, Indianapolis
  • 8Blood and Marrow Transplant Program and Host Defense Program, Divisions of Hematology, Oncology, Bone Marrow Transplant and Infectious Diseases, Nationwide Children’s Hospital, Columbus, Ohio
  • 9Division of Hematology, Oncology and Blood and Marrow Transplantation, Children’s Hospital of Los Angeles, Los Angeles
  • 10Levine Cancer Institute, Atrium Health, Carolinas HealthCare System, Charlotte, North Carolina
  • 11Department of Hematology/Oncology, Hospital Infantil Universitario Niño Jesús, Madrid, Spain
  • 12Division of Pediatric Allergy, Immunology and Bone Marrow Transplantation, Benioff Children’s Hospital, University of California, San Francisco
  • 13The Children’s Hospital at TriStar Centennial Medical Center, Nashville, Tennessee
  • 14Sarah Cannon Research Institute, Nashville, Tennessee
  • 15Texas Transplant Institute, San Antonio
  • 16National Cancer Institute, Bethesda, Maryland
  • 17Division of Cancer Epidemiology & Genetics, National Cancer Institute, Clinical Genetics Branch, Rockville, Maryland
  • 18Hematology Research Centre, Division of Experimental Medicine, Department of Medicine, Imperial College London, London, United Kingdom
  • 19Christian Medical College, Vellore, India
  • 20Hematologic Malignancies & Bone Marrow Transplant, Department of Medicial Oncology, New York-Presbyterian Hospital/Weill Cornell Medical Center, New York
  • 21King Faisal Specialist Hospital, Riyadh, Saudi Arabia
  • 22Division of Hematology/Oncology/ Bone Marrow Transplantation, Department of Medicine, University of Wisconsin Hospital and Clinics, University of Wisconsin, Madison
  • 23Markey Cancer Center, University Kentucky HealthCare, Lexington
  • 24Children’s Hospital Colorado, Denver
  • 25University of Colorado, Denver
  • 26Case Western Reserve University, Cleveland, Ohio
  • 27Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio
  • 28Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children’s Hospital, Cincinnati, Ohio
  • 29Karolinska Institute, Stockholm, Sweden
  • 30Blood and Cancer Centre, Starship Children’s Health, Central Auckland, New Zealand
  • 31Department of Pediatric Hematolgy, Oncology and Blood and Marrow Transplantation, Cleveland Clinic Children’s Hospital, Cleveland, Ohio
  • 32Vanderbilt University, Nashville, Tennessee
  • 33Oregon Health & Science University, Portland
  • 34Roger Williams Cancer Center, Providence, Rhode Island
  • 35Division of Bone Marrow Transplant, Seattle Cancer Care Alliance, Seattle, Washington
  • 36Division of Hematology-Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia
JAMA Pediatr. 2019;173(5):e190081. doi:10.1001/jamapediatrics.2019.0081
Key Points

Question  Have survival rates improved for infants 1 year or younger who received allogeneic hematopoietic cell transplantation (HCT)?

Findings  This cohort study evaluated 2498 infants who received HCT. For infants with nonmalignant diseases, survival rates improved from 2000 through 2004 to 2005 through 2009 and stabilized after this time; for infants with malignant conditions, survival did not improve from 2000 through 2014.

Meaning  Although children and adults who receive HCT are surviving longer than before, infants who need HCT face unique challenges; research to enhance survival should focus on optimizing donor selection, refining conditioning regimens, reducing toxicity, and improving supportive care.


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.