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

Shalini Shenoy, Mary Eapen, Julie A. Panepinto, Brent R. Logan, Juan Wu, Allistair Abraham, Joel Brochstein, Sonali Chaudhury, Kamar Godder, Ann E. Haight, Kimberly A. Kasow, Kathryn Leung, Martin Andreansky, Monica Bhatia, Jignesh Dalal, Hilary Haines, Jennifer Jaroscak, Hillard M. Lazarus, John E. Levine, Lakshmanan KrishnamurtiDavid Margolis, Gail C. Megason, Lolie C. Yu, Michael A. Pulsipher, Iris Gersten, Nancy DiFronzo, Mary M. Horowitz, Mark C. Walters, Naynesh Kamani

Research output: Contribution to journalArticle

68 Citations (Scopus)

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 5 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.

Original languageEnglish (US)
Pages (from-to)2561-2567
Number of pages7
JournalBlood
Volume128
Issue number21
DOIs
StatePublished - Nov 24 2016

Fingerprint

Unrelated Donors
Sickle Cell Anemia
Graft vs Host Disease
Transplants
Grafts
Transplantation
Bone Marrow
Disease-Free Survival
Incidence
Survival Rate
Acute Chest Syndrome
Posterior Leukoencephalopathy Syndrome
Clinical Trials
Premature Mortality
Melphalan
HLA-A Antigens
HLA-B Antigens
Blood
Methylprednisolone
Graft Rejection

ASJC Scopus subject areas

  • Immunology
  • Biochemistry
  • Hematology
  • Cell Biology

Cite this

Shenoy, S., Eapen, M., Panepinto, J. A., Logan, B. R., Wu, J., Abraham, A., ... Kamani, N. (2016). A trial of unrelated donor marrow transplantation for children with severe sickle cell disease. Blood, 128(21), 2561-2567. https://doi.org/10.1182/blood-2016-05-715870

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

In: Blood, Vol. 128, No. 21, 24.11.2016, p. 2561-2567.

Research output: Contribution to journalArticle

Shenoy, 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 2016, 'A trial of unrelated donor marrow transplantation for children with severe sickle cell disease', Blood, vol. 128, no. 21, pp. 2561-2567. https://doi.org/10.1182/blood-2016-05-715870
Shenoy S, Eapen M, Panepinto JA, Logan BR, Wu J, Abraham A et al. A trial of unrelated donor marrow transplantation for children with severe sickle cell disease. Blood. 2016 Nov 24;128(21):2561-2567. https://doi.org/10.1182/blood-2016-05-715870
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. / A trial of unrelated donor marrow transplantation for children with severe sickle cell disease. In: Blood. 2016 ; Vol. 128, No. 21. pp. 2561-2567.
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