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

TitleA trial of unrelated donor marrow transplantation for children with severe sickle cell disease.
Publication TypeJournal Article
Year of Publication2016
AuthorsShenoy, S, Eapen, M, Panepinto, JA, Logan, BR, Wu, J, Abraham, A, Brochstein, J, Chaudhury, S, Godder, K, Haight, AE, Kasow, KA, Leung, K, Andreansky, M, Bhatia, M, Dalal, J, Haines, H, Jaroscak, J, Lazarus, HM, Levine, JE, Krishnamurti, L, Margolis, D, Megason, GC, Yu, LC, Pulsipher, MA, Gersten, I, DiFronzo, N, Horowitz, MM, Walters, MC, Kamani, N
Date Published2016 11 24
KeywordsAdolescent, 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.

Alternate JournalBlood
PubMed ID27625358
PubMed Central IDPMC5123194
Grant ListU10 HL069294 / HL / NHLBI NIH HHS / United States
U10 HL069254 / HL / NHLBI NIH HHS / United States
K12 HD001399 / HD / NICHD NIH HHS / United States
U24 CA076518 / CA / NCI NIH HHS / United States
U10 HL109137 / HL / NHLBI NIH HHS / United States