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Clinical Trial
. 2016 Nov 24;128(21):2561-2567.
doi: 10.1182/blood-2016-05-715870. Epub 2016 Sep 13.

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

Shalini Shenoy  1 , Mary Eapen  2 , Julie A Panepinto  2   3 , Brent R Logan  2 , Juan Wu  4 , Allistair Abraham  5 , Joel Brochstein  6 , Sonali Chaudhury  7 , Kamar Godder  8 , Ann E Haight  9 , Kimberly A Kasow  10 , Kathryn Leung  11 , Martin Andreansky  12 , Monica Bhatia  13 , Jignesh Dalal  14 , Hilary Haines  15 , Jennifer Jaroscak  16 , Hillard M Lazarus  17 , John E Levine  18 , Lakshmanan Krishnamurti  19 , David Margolis  3 , Gail C Megason  20 , Lolie C Yu  21 , Michael A Pulsipher  22 , Iris Gersten  4 , Nancy DiFronzo  23 , Mary M Horowitz  2 , Mark C Walters  24 , Naynesh Kamani  25
Affiliations
Clinical Trial

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

Shalini Shenoy et al. Blood. .

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.

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Figures

Figure 1.
Figure 1.
Probability of EFS and overall survival. The 2-year probability of EFS (A) and overall survival (B) after URD transplant for severe SCD.
Figure 2.
Figure 2.
Probability of GVHD. The 100-day probability of acute GVHD (A) and the 1-year probability of GVHD (B) after URD transplant for severe SCD.
See this image and copyright information in PMC

Comment in

  • Sickle cell disease: the price of cure.
    Roberts I, de la Fuente J. Roberts I, et al. Blood. 2016 Nov 24;128(21):2486-2488. doi: 10.1182/blood-2016-10-740969. Blood. 2016. PMID: 27884835 No abstract available.

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