Higher Risks of Toxicity and Incomplete Recovery in 13-to 17-Year-Old Females after Marrow Donation: RDSafe Peds Results

• Type of Material: Article
• Authors: Michael A. Pulsipher, Children's Hospital Los Angeles; Brent R. Logan, Medical College of Wisconsin; Deidre M. Kiefer, Center for International Blood and Marrow Transplant Research; Pintip Chitphakdithai, Center for International Blood and Marrow Transplant Research; Marcie L. Riches, University of North Carolina; J. Douglas Rizzo, Medical College of Wisconsin; Paolo Anderlini, University of Texas MD Anderson Cancer Center; Susan F. Leitman, National Institutes of Health; James W. Varni, Texas A&M University; Ann Haight, Emory University
• Language: English
• Date: 2019-05-01
• Publisher: Elsevier Science Inc.
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2019 Published by Elsevier Inc. on behalf of 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.2018.12.765
• Title of Journal or Parent Work: Biology of Blood and Marrow Transplantation
• Volume: 25
• Issue: 5
• Start Page: 955
• End Page: 964
• Grant/Funding Information: The CIBMTR is supported primarily by Public Health Service Grant/Cooperative Agreement 5U24CA076518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID); The study was funded by R01 HL085707 through the NHLBI.; *Mediware; The Medical College of Wisconsin; *Merck & Co, Inc.; *Mesoblast; MesoScale Diagnostics, Inc.; Millennium, the Takeda Oncology Co.; *Miltenyi Biotec, Inc.; Mundipharma EDO; National Marrow Donor Program; Novartis Pharmaceuticals Corporation; PCORI; *Pfizer, Inc; *Pharmacyclics, LLC;; *Amgen, Inc.; Anonymous donation to the Medical College of Wisconsin; Astellas Pharma US; Atara Biotherapeutics, Inc.; Be the Match Foundation; *bluebird bio, Inc.; *Bristol Myers Squibb Oncology; *Celgene Corporation; *Chimerix, Inc.; three Grants N00014-17-1-2388, N00014–17-1-2850 and N00014-18-1-2045 from the Office of Naval Research; and grants from Adaptive Biotechnologies; PIRCHE AG; *Sanofi Genzyme; *Seattle Genetics; Shire; Spectrum Pharmaceuticals, Inc.; St. Baldrick’s Foundation; Swedish Orphan Biovitrum, Inc.; *Takeda Oncology; and University of Minnesota.; Additional funding for MAP was provided by 2UG1HL069254 (NHLBI/NCI) and the Johnny Crisstopher Children’s Charitable Foundation St. Baldrick’s Consortium Grant.; a contract HHSH250201700006C with Health Resources and Services Administration (HRSA/DHHS); a Grant/Cooperative Agreement 1U24HL138660 from NHLBI and NCI; *CytoSen Therapeutics, Inc.; Fred Hutchinson Cancer Research Center; Gamida Cell Ltd.; Gilead Sciences, Inc.; HistoGenetics, Inc.; Immucor; *Incyte Corporation; Janssen Scientific Affairs, LLC; *Jazz Pharmaceuticals, Inc.; Karius, Inc.; Karyopharm Therapeutics, Inc.; *Kite Pharma, Inc.; Medac, GmbH
• Keywords: Stem cell transplantation; BM collection toxicities; Transplantation; Stem-cell transplantation; Colony stimulating factor; Life Sciences & Biomedicine; Collection; Prospective trial; Immunology; Primed bone marrow; Hematology; Mobilization; Pediatric blood; PBSC collection toxicities; Donors; Adverse events; Donor safety; Safety; Science & Technology
• Research Categories: Health Sciences, Medicine and Surgery; Health Sciences, Pathology; Health Sciences, Immunology; Health Sciences, Toxicology

Abstract

Although donation of bone marrow (BM)or peripheral blood stem cells (PBSCs)from children to family members undergoing allogeneic transplantation are well-established procedures, studies detailing levels of pain, symptoms, and long-term recovery are lacking. To address this lack, we prospectively enrolled 294 donors age <18 years at 25 pediatric transplantation centers in North America, assessing them predonation, peridonation, and at 1 month, 6 months, and 1 year postdonation. We noted that 71% of children reported pain and 59% reported other symptoms peridonation, with resolution to 14% and 12% at 1 month postdonation. Both older age (age 13 to 17 years versus younger)and female sex were associated with higher levels of pain peridonation, with the highest rates in older females (57% with grade 2-4 pain and 17% with grade 3-4 pain). Multivariate analyses showed a 4-fold increase in risk for older females compared with males age <13 years (P <.001). At 1 year, 11% of 13- to 17-year-old females reported grade 2-4 pain, compared with 3% of males age 13 to 17 years, 0% of females age <13 years, and 1% of males age <13 years (P =.01). Males and females age 13 to 17 years failed to return to predonation pain levels at 1 year 22% and 23% of the time, respectively, compared with 3% and 10% in males and females age <13 years (P =.002). Our data show that females age 13 to 17 years are at increased risk of grade 2-4 pain at 1 year and >20% of females and males age 13 to 17 years do not return to baseline pain levels by 1 year after BM donation. Studies aimed at decreasing symptoms and improving recovery in older children are warranted.