Birth Order and Transplantation Outcome in HLA-Identical Sibling Stem Cell Transplantation: An Analysis on Behalf of the Center for International Blood and Marrow Transplantation

• Type of Material: Article
• Authors: Christiane Dobbelstein, Hannover Medical School; Kwang Woo Ahn, Medical College of Wisconsin; Michael Haagenson, Center for International Blood and Marrow Transplant Research; Gregory A. Hale, University of South Florida; Jon J. van Rood, Leiden University; David Miklos, Stanford University; Edmund K Waller, Emory University; Stephen R. Spellman, Center for International Blood and Marrow Transplant Research; Marcelo Fernandez-Vina, Stanford University; Arnold Ganser, Hannover Medical School; Mahmoud Aljurf, King Faisal Specialist Hospital and Research Centre; Martin Bornhaeuser, University Hospital Carl Gustav Carus; Vikas Gupta, Princess Margaret Hospital; Susan Marino, University of Chicago; Marilyn S. Pollack, University of Texas Health Science Center; Vijay Reddy, Florida Center for Cellular Therapy; Matthias Eder, Hannover Medical School; Stephanie J. Lee, Fred Hutchinson Cancer Research Center
• Language: English
• Date: 2013-05-01
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2013 American Society for Blood and Marrow Transplantation.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.bbmt.2013.01.020
• Title of Journal or Parent Work: Biology of Blood and Marrow Transplantation
• ISSN: 1083-8791
• Volume: 19
• Issue: 5
• Start Page: 741
• End Page: 745
• Grant/Funding Information: The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement U24-CA76518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI), and the National Institute of Allergy and Infectious Diseases (NIAID); a Grant/Cooperative Agreement 5U01HL069294 from NHLBI and NCI; contract HHSH234200637015C with Health Resources and Services Administration (HRSA/DHHS); grants N00014-06-1-0704 and N00014-08-1-0058 from the Office of Naval Research; and grants from AABB; Allos Inc; Amgen Inc; an anonymous donation to the Medical College of Wisconsin; Astellas Pharma US Inc; Be the Match Foundation; Biogen Idec Inc; BioMarin Pharmaceutical Inc; Biovitrum AB; Blood Center of Wisconsin; Blue Cross and Blue Shield Association; Bone Marrow Foundation; Buchanan Family Foundation; CaridianBCT; Celgene Corporation; CellGenix GmbH; Children's Leukemia Research Association; ClinImmune Labs; CTI Clinical Trial and Consulting Services; Eisai Inc; Genentech Inc; Genzyme Corporation; Histogenetics Inc; HKS Medical Information Systems; Hospira Inc; Kirin Brewery Co Ltd; The Leukemia & Lymphoma Society; Merck & Company; The Medical College of Wisconsin; Millennium Pharmaceuticals Inc; Miller Pharmacal Group; Milliman USA Inc; Miltenyi Biotec Inc; National Marrow Donor Program; Nature Publishing Group; Novartis Oncology; Oncology Nursing Society; Osiris Therapeutics Inc; Otsuka America Pharmaceutical Inc; Pall Life Sciences; Pfizer Inc; Schering Corporation; Sigma-Tau Pharmaceuticals; Soligenix Inc; StemCyte Inc; StemSoft Software Inc; Sysmex America Inc; Therakos Inc; Vidacare Corporation; ViraCor Laboratories; ViroPharma Inc; and Wellpoint Inc.
• Keywords: Transplantation; MICROCHIMERISM; BONE-MARROW; Life Sciences & Biomedicine; Science & Technology; Microchimerism; Immunology; T-CELLS; PREGNANCY; DONOR; VERSUS-HOST-DISEASE; Donor; CORD BLOOD; RECIPIENTS; RISK-FACTORS; TRAFFICKING; Hematology; Hematopoietic stem cell transplantation graft-versus-host-disease
• Research Categories: Health Sciences, Immunology; Health Sciences, Medicine and Surgery

Abstract

Allogeneic stem cell transplantation (SCT) is the most effective treatment option for many hematologic malignancies, but graft-versus-host disease (GVHD) remains a major cause of treatment failure. Along with well-established risk factors for transplantation outcomes, recent single-center studies have identified a birth order effect in HLA-identical sibling SCT, with lower rates of acute and chronic GVHD and improved overall survival when the donor is younger than the recipient. One hypothesized mechanism for this effect is microchimerism due to fetomaternal and transmaternal sibling cell trafficking during pregnancy as the donor is exposed to recipient antigens in utero. The aim of the present study was to validate previously reported single-center data in a large, multicenter cohort provided by the Center for International Blood and Marrow Transplantation. All adult and pediatric patients (n = 11,365) with a hematologic malignancy who underwent allogeneic SCT with a graft from an HLA-identical sibling donor between 1990 and 2007 were included. When donors were younger than recipients, there was a significantly lower rate of acute GVHD grade II-IV and chronic GVHD in children, as well as a lower rate of chronic GVHD in adolescents. However, the hypothesized overall positive effect of lower relapse and better survival when donors are younger than recipients was not observed. Our data suggest that if otherwise equally matched, a graft from a younger sibling may be superior to a graft from an older sibling for children and adolescents undergoing SCT.