Allogeneic hematopoietic stem-cell transplantation for sickle cell disease

Matthew M. Hsieh, Elizabeth M. Kang, Courtney D. Fitzhugh, M. Beth Link, Charles D. Bolan, Roger Kurlander, Richard W. Childs, Griffin P. Rodgers, Jonathan D. Powell, John F. Tisdale

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND: Myeloablative allogeneic hematopoietic stem-cell transplantation is curative in children with sickle cell disease, but in adults the procedure is unduly toxic. Graft rejection and graft-versus-host disease (GVHD) are additional barriers to its success. We performed nonmyeloablative stem-cell transplantation in adults with sickle cell disease. METHODS: Ten adults (age range, 16 to 45 years) with severe sickle cell disease underwent non-myeloablative transplantation with CD34+ peripheral-blood stem cells, mobilized by granulocyte colony-stimulating factor (G-CSF), which were obtained from HLA-matched siblings. The patients received 300 cGy of total-body irradiation plus alemtuzumab before transplantation, and sirolimus was administered afterward. RESULTS: All 10 patients were alive at a median follow-up of 30 months after transplantation (range, 15 to 54). Nine patients had long-term, stable donor lymphohematopoietic engraftment at levels that sufficed to reverse the sickle cell disease phenotype. Mean (±SE) donor-recipient chimerism for T cells (CD3+) and myeloid cells (CD14+15+) was 53.3±8.6% and 83.3±10.3%, respectively, in the nine patients whose grafts were successful. Hemoglobin values before transplantation and at the last follow-up assessment were 9.0±0.3 and 12.6±0.5 g per deciliter, respectively. Serious adverse events included the narcotic-withdrawal syndrome and sirolimus-associated pneumonitis and arthralgia. Neither acute nor chronic GVHD developed in any patient. CONCLUSIONS: A protocol for nonmyeloablative allogeneic hematopoietic stem-cell transplantation that includes total-body irradiation and treatment with alemtuzumab and sirolimus can achieve stable, mixed donor-recipient chimerism and reverse the sickle cell phenotype. (ClinicalTrials.gov number, NCT00061568.).

Original languageEnglish (US)
Pages (from-to)2309-2317
Number of pages9
JournalNew England Journal of Medicine
Volume361
Issue number24
DOIs
StatePublished - Dec 10 2009

ASJC Scopus subject areas

  • Medicine(all)

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