Matched Related Donor Transplants for Sickle Cell Disease: Report from the Center for International Blood and Transplant Research.

Allogeneic hematopoietic cell transplantation (HCT) is the only known therapy to cure sickle cell disease though few patients receive this therapy. We report outcomes after HLA-matched sibling HCT in 68 patients with sickle cell disease, transplanted in 1989 to 2002. Of these, 33 (49%) were transplanted between 1999 and 2002. Median age at transplantation was 10 (range 2–30) years. Hemoglobin SS was the predominant genotype. Indications for HCT were predominately stroke (n=24) and recurrent vaso-occlusive crises (n=24); others included acute chest syndrome, increasing transfusion requirement, progressive iron overload and recurrent priapism. Forty-four patients (66%) received ≥ 10 red blood cell transfusions prior to HCT. Twenty patients (26%) had poor performance scores prior to transplantation. Busulfan and cyclophosphamide was the most frequently used conditioning regimen (n=63, 92%). Fifty-five patients (81%) received bone marrow allografts, 9 patients (13%) received mobilized peripheral blood, 3 patients (4%) received umbilical cord blood, and 1 patient received umbilical cord blood and bone marrow from the same donor. All patients achieved neutrophil recovery and the probability of platelet recovery ≥20,000/ul at day 100 was 93% (95% confidence interval [CI], 86–98)%. The probabilities of grades 2–4 acute graft-versus-host disease (GVHD) at day 100 and chronic GVHD at 5 years were 10% (95% CI, 4–19%) and 22% (95% CI, 12–33%), respectively. Sixty-five of 68 patients are alive after HCT with a median follow up of 5 years. The 5-year probabilities of overall and disease-free survival were 97% (95% CI, 88–100%) and 84% (95% CI, 75–95%), respectively. We defined treatment failure (inverse of disease-free survival) as death from any cause or disease recurrence defined as having a hemoglobin S >50%. Recurrent disease was the predominant cause of treatment failure (n=10). Of these 10 patients, 8 had return of clinical symptoms and the remaining 2 were symptom-free. Among patients with recurrent disease, 5 had received >10 red blood cell transfusions pre-transplant and 1 was reported to have red blood cell alloantibodies. Four patients with recurrent disease were transplanted for stroke and 6 for vaso-occlusive crisis. Nine of 10 patients received busulfan and cyclophosphamide for their conditioning and the remaining patient, total body irradiation 200cGy (single fraction), fludarabine and anti-thymocyte globulin. Three patients died; all deaths occurred more than 100 days after HCT. Causes of death were hemorrhage (n=1), multi-organ failure (n=1) and unknown (n=1). Of the 10 patients with stroke that had magnetic resonance imaging (MRI) of the brain pre- and post-transplant, 8 showed stable disease post transplant, one showed improvement and one had a worsening MRI. Overall survival after HCT for sickle cell disease is excellent, however recurrent disease and chronic GVHD remain a concern. Future studies should focus on strategies aimed at reducing disease recurrence.