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Blood. 2016 Nov 24;128(21):2561-2567. Epub 2016 Sep 13.

A trial of unrelated donor marrow transplantation for children with severe sickle cell disease.

Author information

1
Department of Pediatrics, Washington University School of Medicine, St. Louis Children's Hospital, St. Louis, MO.
2
Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI.
3
Children's Hospital of Wisconsin, Milwaukee, WI.
4
The Emmes Corporation, Rockville, MD.
5
Children's National Medical Center, Washington, DC.
6
Steven and Alexandra Cohen Children's Medical Center, New Hyde Park, NY.
7
Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL.
8
Department of Pediatrics, Virginia Commonwealth University, Richmond, VA.
9
Department of Pediatrics, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA.
10
Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC.
11
Department of Pediatrics, Baylor College of Medicine, Houston, TX.
12
Department of Pediatrics, University of Miami, Miami, FL.
13
Columbia University Medical Center, New York, NY.
14
Children's Mercy Hospital and Clinics, Kansas City, KS.
15
Department of Pediatrics, University of Alabama, Birmingham, AL.
16
Department of Pediatrics, Medical University of South Carolina, Charleston, SC.
17
Department of Internal Medicine, University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, OH.
18
Departments of Internal Medicine and Pediatrics, University of Michigan, Ann Arbor, MI.
19
Children's Hospital of Pittsburgh, Pittsburgh, PA.
20
University of Mississippi Medical Center, Jackson, MS.
21
Louisiana State University Medical Center, Children's Hospital of New Orleans, New Orleans, LA.
22
Pediatric Blood and Marrow Transplant Consortium, Salt Lake City, UT.
23
National Heart, Lung, and Blood Institute, Bethesda, MD.
24
UCSF Benioff Children's Hospital, Oakland, CA; and.
25
AABB Center for Cellular Therapies, Bethesda, MD.

Abstract

Children with sickle cell disease experience organ damage, impaired quality of life, and premature mortality. Allogeneic bone marrow transplant from an HLA-matched sibling can halt disease progression but is limited by donor availability. A Blood and Marrow Transplant Clinical Trials Network (BMT CTN) phase 2 trial conducted from 2008 to 2014 enrolled 30 children aged 4 to 19 years; 29 were eligible for evaluation. The primary objective was 1-year event-free survival (EFS) after HLA allele-matched (at HLA-A, -B, -C, and -DRB1 loci) unrelated donor transplant. The conditioning regimen included alemtuzumab, fludarabine, and melphalan. Graft-versus-host disease (GVHD) prophylaxis included calcineurin inhibitor, short-course methotrexate, and methylprednisolone. Transplant indications included stroke (n = 12), transcranial Doppler velocity >200 cm/s (n = 2), ≥3 vaso-occlusive pain crises per year (n = 12), or ≥2 acute chest syndrome episodes (n = 4) in the 2 years preceding enrollment. Median follow-up was 26 months (range, 12-62 months); graft rejection was 10%. The 1- and 2-year EFS rates were 76% and 69%, respectively. The corresponding rates for overall survival were 86% and 79%. The day 100 incidence rate of grade II-IV acute GVHD was 28%, and the 1-year incidence rate of chronic GVHD was 62%; 38% classified as extensive. There were 7 GVHD-related deaths. A 34% incidence of posterior reversible encephalopathy syndrome was noted in the first 6 months. Although the 1-year EFS met the prespecified target of ≥75%, this regimen cannot be considered sufficiently safe for widespread adoption without modifications to achieve more effective GVHD prophylaxis. The BMT CTN #0601 trial was registered at www.clinicaltrials.gov as #NCT00745420.

PMID:
27625358
PMCID:
PMC5123194
DOI:
10.1182/blood-2016-05-715870
[Indexed for MEDLINE]
Free PMC Article

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