Suhag H Parikh1, Prakash Satwani2, Kwang Woo Ahn3, Natasha A Sahr4, Caitrin Fretham5, Allistair A Abraham6, Vaibhav Agrawal7, Jeffery J Auletta8, Hisham Abdel-Azim9, Edward Copelan10, Miguel-Angel Diaz11, Christopher C Dvorak12, Haydar A Frangoul13,14, Cesar O Freytes15, Shahinaz M Gadalla16,17, Robert Peter Gale18, Biju George19, Usama Gergis20, Shahrukh Hashmi21, Peiman Hematti22, Gerhard C Hildebrandt23, Amy K Keating24,25, Hillard M Lazarus26, Kasiani C Myers27,28, Richard F Olsson29, Timothy Prestidge30, Seth J Rotz31, Bipin N Savani32, Evan B Shereck33,34, Kirsten M Williams6, Baldeep Wirk35, Marcelo C Pasquini3, Alison W Loren36. 1. Department of Pediatric Blood and Marrow Transplant, Duke University Medical Center, Durham, North Carolina. 2. Division of Pediatric Hematology, Oncology and Stem Cell Transplantation, Department of Pediatrics, Columbia University Medical Center, New York, New York. 3. Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee. 4. St Jude Children's Research Hospital, Memphis, Tennessee. 5. Center for International Blood and Marrow Transplant Program, National Marrow Donor Program/Be the Match, Minneapolis, Minnesota. 6. Division of Blood and Marrow Transplantation, Center for Cancer and Blood Disorders, Children's National Health System, Washington, DC. 7. Indiana University, Indianapolis. 8. Blood and Marrow Transplant Program and Host Defense Program, Divisions of Hematology, Oncology, Bone Marrow Transplant and Infectious Diseases, Nationwide Children's Hospital, Columbus, Ohio. 9. Division of Hematology, Oncology and Blood and Marrow Transplantation, Children's Hospital of Los Angeles, Los Angeles. 10. Levine Cancer Institute, Atrium Health, Carolinas HealthCare System, Charlotte, North Carolina. 11. Department of Hematology/Oncology, Hospital Infantil Universitario Niño Jesús, Madrid, Spain. 12. Division of Pediatric Allergy, Immunology and Bone Marrow Transplantation, Benioff Children's Hospital, University of California, San Francisco. 13. The Children's Hospital at TriStar Centennial Medical Center, Nashville, Tennessee. 14. Sarah Cannon Research Institute, Nashville, Tennessee. 15. Texas Transplant Institute, San Antonio. 16. National Cancer Institute, Bethesda, Maryland. 17. Division of Cancer Epidemiology & Genetics, National Cancer Institute, Clinical Genetics Branch, Rockville, Maryland. 18. Hematology Research Centre, Division of Experimental Medicine, Department of Medicine, Imperial College London, London, United Kingdom. 19. Christian Medical College, Vellore, India. 20. Hematologic Malignancies & Bone Marrow Transplant, Department of Medicial Oncology, New York-Presbyterian Hospital/Weill Cornell Medical Center, New York. 21. King Faisal Specialist Hospital, Riyadh, Saudi Arabia. 22. Division of Hematology/Oncology/ Bone Marrow Transplantation, Department of Medicine, University of Wisconsin Hospital and Clinics, University of Wisconsin, Madison. 23. Markey Cancer Center, University Kentucky HealthCare, Lexington. 24. Children's Hospital Colorado, Denver. 25. University of Colorado, Denver. 26. Case Western Reserve University, Cleveland, Ohio. 27. Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio. 28. Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital, Cincinnati, Ohio. 29. Karolinska Institute, Stockholm, Sweden. 30. Blood and Cancer Centre, Starship Children's Health, Central Auckland, New Zealand. 31. Department of Pediatric Hematolgy, Oncology and Blood and Marrow Transplantation, Cleveland Clinic Children's Hospital, Cleveland, Ohio. 32. Vanderbilt University, Nashville, Tennessee. 33. Oregon Health & Science University, Portland. 34. Roger Williams Cancer Center, Providence, Rhode Island. 35. Division of Bone Marrow Transplant, Seattle Cancer Care Alliance, Seattle, Washington. 36. Division of Hematology-Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia.
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.
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: Hemalatha G Rangarajan; Marcelo S F Pereira; Ruta Brazauskas; Andrew St Martin; Ashleigh Kussman; Ezgi Elmas; Michael R Verneris; Shahinaz M Gadalla; Steven G E Marsh; Sophie Paczesny; Stephen R Spellman; Stephanie J Lee; Dean A Lee Journal: Transplant Cell Ther Date: 2021-08-15
Authors: Kira Bona; Ruta Brazauskas; Naya He; Leslie Lehmann; Hisham Abdel-Azim; Ibrahim A Ahmed; A Samer Al-Homsi; Mahmoud Aljurf; Staci D Arnold; Sherif M Badawy; Minoo Battiwalla; Sara Beattie; Neel S Bhatt; Jignesh Dalal; Christopher E Dandoy; Miguel Angel Diaz; Haydar A Frangoul; César O Freytes; Siddhartha Ganguly; Biju George; David Gomez-Almaguer; Theresa Hahn; Rammurti T Kamble; Jennifer M Knight; C Fred LeMaistre; Jason Law; Hillard M Lazarus; Navneet S Majhail; Richard F Olsson; Jaime Preussler; Bipin N Savani; Raquel Schears; Sachiko Seo; Akshay Sharma; Alok Srivastava; Amir Steinberg; David Szwajcer; Baldeep Wirk; Ayami Yoshimi; Nandita Khera; William A Wood; Shahrukh Hashmi; Christine N Duncan; Wael Saber Journal: Blood Date: 2021-01-28 Impact factor: 25.476