The Impact of Donor Type on Outcomes and Cost of Allogeneic Hematopoietic Cell Transplantation for Pediatric Leukemia: A Merged Center for International Blood and Marrow Transplant Research and Pediatric Health Information System Analysis

• Type of Material: Article
• Authors: Staci Arnold, Emory University; Ruta Brazauskas, Medical College of Wisconsin; Naya He, Medical College of Wisconsin; Yimei Li, University of Pennsylvania; Matt Hall, Children’s Hospital Association; Yoshiko Atsuta, Japanese Data Ctr Hematopoiet Cell Transplantat; Jignesh Dalal, Rainbow Babies & Children’s Hospital; Theresa Hahn, Roswell Park Cancer Institute, Buffalo; Nandita Khera, Mayo Clinic; Carmem Bonfim, University of Parana; Shahrukh Hashmi, King Faisal Specialist Hospital and Research Center, Riydah; Susan Parsons, Tufts Medical Center; William A Wood, University of North Carolina; Amir Steinberg, Mount Saini Hospital; César O Freytes, Texas Transplant Institute; Christopher E Dandoy, University of Cincinnati; David Marks, University Hospitals Bristol NHS Trust; Hillard M Lazarus, Case Western Reserve University; Hisham Abdel-Azim, University of Southern California; Menachem Bitan, Tel-Aviv Sourasky Medical Center; Miguel Angel Diaz, Hospital Infantil Universitario Nino Jesus; Richard F Olsson, Karolinska Institutet; Usama Gergis, Thomas Jefferson University; Adriana Seber, Hospital Samaritano de São Paulo; Baldeep Wirk, Penn State Cancer Institute; Fred C LeMaistre, Sarah Cannon Blood Cancer Network; Celalettin Ustun, Rush University; Christine Duncan, Boston Childrens Hospital; David Rizzieri, Duke University; David Szwajcer, University of Manitoba; Franca Fagioli, Regina Margherita Children Hospital; Haydar Frangoul, The Children’s Hospital at TriStar Centennial Medical Center; Jennifer M Knight, Medical College of Wisconsin; Rammurti T Kamble, Baylor College of Medicine; Paulette Mehta, Central Arkansas Veterans Healthcare System; Raquel Schears, University of Central Florida; Prakash Satwani, Columbia University; Michael A Pulsipher, University of Southern California; Richard Aplenc, University of Pennsylvania; Wael Saber, Medical College of Wisconsin
• Language: English
• Date: 2020-09-01
• Publisher: ELSEVIER SCIENCE INC
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2020 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.bbmt.2020.05.016
• Title of Journal or Parent Work: BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
• Volume: 26
• Issue: 9
• Start Page: 1747
• End Page: 1756
• Grant/Funding Information: Dr. Arnold was supported in part by a Robert Wood Johnson Foundation Harold Amos Medical Faculty Development Program award. Dr. Aplenc was supported by 1R01CA166581.; The CIBMTR is supported primarily by Public Health Service U24CA076518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID); U24HL138660 from NHLBI and NCI; OT3HL147741, R21HL140314 and U01HL128568 from the NHLBI; HHSH250201700006C, SC1MC31881-01-00 and HHSH250201700007C from the Health Resources and Services Administration (HRSA); and N00014-18-1-2850, N00014-18-1-2888, and N00014-20-1-2705 from the Office of Naval Research; Additional federal support is provided by P01CA111412, R01CA152108, R01CA215134, R01CA218285, R01CA231141, R01HL126589, R01AI128775, R01HL129472, R01HL130388, R01HL131731, U01AI069197, U01AI126612, and BARDA. Support is also provided by Be the Match Foundation, Boston Children’s Hospital, Dana Farber, Japan Hematopoietic Cell Transplantation Data Center, St. Baldrick’s Foundation, the National Marrow Donor Program, the Medical College of Wisconsin and from the following commercial entities: AbbVie; Actinium Pharmaceuticals, Inc.; Adaptive Biotechnologies; Adienne SA; Allovir, Inc.; Amgen, Inc.; Anthem, Inc.; Astellas Pharma US; AstraZeneca; Atara Biotherapeutics, Inc.; bluebird bio, Inc.; Bristol Myers Squibb Co.; Celgene Corp.; Chimerix, Inc.; CSL Behring; CytoSen Therapeutics, Inc.; Daiichi Sankyo Co., Ltd.; Gamida-Cell, Ltd.; Genzyme; GlaxoSmithKline (GSK); HistoGenetics, Inc.; Incyte Corporation; Janssen Biotech, Inc.; Janssen Pharmaceuticals, Inc.; Janssen/Johnson & Johnson; Jazz Pharmaceuticals, Inc.; Kiadis Pharma; Kite Pharma; Kyowa Kirin; Legend Biotech; Magenta Therapeutics; Mallinckrodt LLC; Medac GmbH; Merck & Company, Inc.; Merck Sharp & Dohme Corp.; Mesoblast; Millennium, the Takeda Oncology Co.; Miltenyi Biotec, Inc.; Novartis Oncology; Novartis Pharmaceuticals Corporation; Omeros Corporation; Oncoimmune, Inc.; Orca Biosystems, Inc.; Pfizer, Inc.; Phamacyclics, LLC; Regeneron Pharmaceuticals, Inc.; REGiMMUNE Corp.; Sanofi Genzyme; Seattle Genetics; Sobi, Inc.; Takeda Oncology; Takeda Pharma; Terumo BCT; Viracor Eurofins and Xenikos BV. The views expressed in this article do not reflect the official policy or position of the National Institute of Health, the Department of the Navy, the Department of Defense, Health Resources and Services Administration (HRSA) or any other agency of the U.S. Government.
• Keywords: Stem cell transplant; Hematology; Life Sciences & Biomedicine; Transplantation; CLINICAL-TRIAL; SURVIVAL; Outcomes; Hematopoietic cell transplant; CORD BLOOD; RACE; Bone marrow transplant; Donor type; CHILDREN; ADOLESCENTS; Acute leukemia; T-CELL; ACUTE LYMPHOBLASTIC-LEUKEMIA; Transplant; Immunology; Healthcare utilization; Science & Technology; Cost; RISKS; Pediatric; PLATFORM

Abstract

Allogeneic hematopoietic stem cell transplantation (alloHCT) may be associated with significant morbidity and mortality, resulting in increased healthcare utilization (HCU). To date, no multicenter comparative cost analyses have specifically evaluated alloHCT in children with acute leukemia. In this retrospective cohort study, we examined the relationship between survival and HCU while investigating the hypothesis that matched sibling donor (MSD) alloHCT has significantly lower inpatient HCU with unrelated donor (URD) alloHCT, and that among URDs, umbilical cord blood (UCB) alloHCT will have higher initial utilization but lower long-term utilization. Clinical and transplantation outcomes data from the Center for International Blood and Marrow Transplant Research (CIBMTR) were merged with inpatient cost data from the Pediatric Health Information System (PHIS) database using a probabilistic merge methodology. The merged dataset comprised US patients age 1 to 21 years who underwent alloHCT for acute leukemia between 2004 and 2011 with comprehensive CIBMTR data at a PHIS hospital. AlloHCT was analyzed by donor type, with specific analysis of utilization and costs using PHIS claims data. The primary outcomes of overall survival (OS), leukemia-free survival (LFS), and inpatient costs were evaluated using Kaplan-Meier curves and Cox and Poisson models. A total of 632 patients were identified in both the CIBMTR and PHIS data. The 5-year LFS was 60% for MSD alloHCT, 47% for well-matched matched unrelated donor bone marrow (MUD) alloHCT, 48% for mismatched unrelated donor alloHCT, and 45% for UCB alloHCT (P = .09). Total adjusted costs were significantly lower for MSD alloHCT versus MUD alloHCT by day 100 (adjusted cost ratio [ACR], .73; 95% confidence interval [CI], .62 to .86; P < .001), and higher for UCB alloHCT versus MUD alloHCT (ACR, 1.27; 95% CI, 1.11 to 1.45; P < .001). By 2 years, total adjusted costs remained significantly lower for MSD alloHCT compared with MUD alloHCT (ACR, .67; 95% CI, .56 to .81; P < .001) and higher for UCB alloHCT compared with MUD alloHCT (ACR, 1.25; 95% CI, 1.02 to 1.52; P = .0280). Our data show that UCB and MUD alloHCT provide similar survival outcomes; however, MUD alloHCT has a significant advantage in cost by day 100 and 2 years. More research is needed to determine whether the cost difference among URD alloHCT approaches remains significant with a larger sample size and/or beyond 2 years post-alloHCT.