Bone marrow transplantation for adolescents and young adults with sickle cell disease: Results of a prospective multicenter pilot study

• Type of Material: Article
• Authors: Lakshmanan Krishnamurti, Emory University; Donna S. Neuberg, Dana Farber Cancer Institute; Keith M. Sullivan, Duke University; Naynesh R. Kamani, Children's National Health System; Allistair Abraham, University of Pittsburgh; Federico Campigotto, Dana Farber Cancer Institute; Wandi Zhang, Dana Farber Cancer Institute; Thabat Dandoul, University of Colorado; Laura De Castro, City of Hope Hospital; Suhag Parikh, Duke University; Nitya Bakshi, Emory University; Ann Haight, Emory University; Kathryn L. Hassell, Virginia Commonwealth University; Rebekah Loving, Virginia Commonwealth University; Joseph Rosenthal, Emory University; Shannon L. Smith, Emory University; Wally Smith, UCSF Benioff Childrens Hosp Oakland; Marcus Spearman, Dana Farber Canc Inst; Kristen Stevenson, Dana Farber Canc Inst; Catherine J Wu, UCSF Benioff Children's Hospital of Oakland; Christina Wiedl, Emory University; Edmund Waller, UCSF Benioff Children's Hospital of Oakland; Mark C. Walters
• Language: English
• Date: 2019-04-01
• Publisher: Wiley: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2019 Wiley Periodicals, Inc.
• Final Published Version (URL): http://dx.doi.org/10.1002/ajh.25401
• Title of Journal or Parent Work: American Journal of Hematology
• ISSN: 0361-8609
• Volume: 94
• Issue: 4
• Start Page: 446
• End Page: 454
• Grant/Funding Information: Supported by a grant from the National Heart, Lung, and Blood Institute (R34-HL108761).
• Keywords: MORPHOLOGY; PULMONARY; Science & Technology; DEATH; MORTALITY; HEALTH SURVEY SF-36; Hematology; CHIMERISM; Life Sciences & Biomedicine; DAILY IV-BUSULFAN; CHILDREN; QUALITY-OF-LIFE; CHRONIC HEPATITIS
• Research Categories: Biology, Biostatistics; Health Sciences, Medicine and Surgery

Abstract

We conducted a multicenter pilot investigation of the safety and feasibility of bone marrow transplantation (BMT) in adults with severe sickle cell disease (SCD) (NCT 01565616) using a reduced toxicity preparative regimen of busulfan (13.2 mg/kg), fludarabine (175 mg/m 2 ) and thymoglobulin (6 mg/kg) and cyclosporine or tacrolimus and methotrexate for graft-vs-host disease (GVHD) prophylaxis. Twenty-two patients (median age 22 years; range 17-36) were enrolled at eight centers. Seventeen patients received marrow from an HLA-identical sibling donor and five patients received marrow from an 8/8 HLA-allele matched unrelated donor. Before BMT, patients had stroke, acute chest syndrome, recurrent pain events, were receiving regular red blood cell transfusions, or had an elevated tricuspid regurgitant jet (TRJ) velocity, which fulfilled eligibility criteria. Four patients developed grades II-III acute GVHD (18%) and six developed chronic GVHD (27%) that was moderate in two and severe in one patient. One patient died of intracranial hemorrhage and one of GVHD. Nineteen patients had stable donor chimerism, 1-year post-transplant. One patient who developed secondary graft failure survives disease-free after a second BMT. The one-year overall survival and event-free survival (EFS) are 91% (95% CI 68%-98%) and 86% (95% CI, 63%-95%), respectively, and 3-year EFS is 82%. Statistically significant improvements in the pain interference and physical function domains of health-related quality of life were observed. The study satisfied the primary endpoint of 1-year EFS ≥70%. This regimen is being studied in a prospective clinical trial comparing HLA-matched donor BMT with standard of care in adults with severe SCD (NCT02766465).