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

Publication Type
Journal Article
Year of Publication
Shenoy, Shalini; Eapen, Mary; Panepinto, Julie A; Logan, Brent R; Wu, Juan; Abraham, Allistair; Brochstein, Joel; Chaudhury, Sonali; Godder, Kamar; Haight, Ann E; Kasow, Kimberly A; Leung, Kathryn; Andreansky, Martin; Bhatia, Monica; Dalal, Jignesh; Haines, Hilary; Jaroscak, Jennifer; Lazarus, Hillard M; Levine, John E; Krishnamurti, Lakshmanan; Margolis, David; Megason, Gail C; Yu, Lolie C; Pulsipher, Michael A; Gersten, Iris; DiFronzo, Nancy; Horowitz, Mary M; Walters, Mark C; Kamani, Naynesh
Date Published
2016 11 24
Adolescent; Allografts; Anemia, Sickle Cell; Bone Marrow Transplantation; Calcineurin Inhibitors; Child; Disease-Free Survival; Female; Follow-Up Studies; Graft vs Host Disease; Humans; Male; Survival Rate; Unrelated Donors

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.