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

Shenoy, S.; Eapen, M.; Panepinto, J. A.; Logan, B. R.; Wu, J.; Abraham, A.; Brochstein, J.; Chaudhury, S.; Godder, K.; Haight, A. E.; Kasow, K. A.; Leung, K.; Andreansky, M.; Bhatia, M.; Dalal, J.; Haines, H.; Jaroscak, J.; Lazarus, H. M.; Levine, J. E.; Krishnamurti, L.; Margolis, D.; Megason, G. C.; Yu, L. C.; Pulsipher, M. A.; Gersten, I.; DiFronzo, N.; Horowitz, M. M.; Walters, M. C.; Kamani, N.

Blood. 2016 Sep 15; 128(21):2561-2567


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.

Read More on PubMed