Work

221: Preliminary Results of Non-Ablative Conditioning (NAC) with Busulfan (Bu), Fludarabine (Flu) and Alemtuzumab followed by Allogeneic Stem Cell Transplantation (AlloSCT) to Induce Mixed Donor Chimerism in Patients with Sickle Cell Disease (SCD)

Year: 2008

Type: article

Abstract: SCD is associated with a decrease in lifespan and quality of life in children. The only known cure is AlloSCT from a matched family donor with only 15% of patients having an unaffected, HLA-matched identical sibling. Patients undergoing myeloablative AlloSCT are at risk for numerous complications post SCT including death, graft versus host disease (GVHD), and infections. Full donor chimerism is not necessary to correct the underlying genetic defect and eliminate symptoms in patients with SCD. In this study, we report the preliminary results of NAC and AlloSCT from related matched family and unrelated umbilical cord blood (UCB) donors in 7 patients (7M:0F) with high risk SCD (HbSS = 4, HbSC = 2, HbSßThal = 1). Conditioning was Bu (4 mg/kg × 4 d ≤ 4 yrs and 12.8 mg/kg × 4 d > 4 yrs), Flu (30 mg/m2 × 6 d), and Alemtuzumab (2 mg/m2 × 1 d, 6 mg/m2 × 2 d, and 25 mg/m2 × 2 d). UCB recipients also received rabbit antithymocyte globulin (2 mg/kg × 4 d). Mean age was 5.8 years +/-4.03 (1.4–13.75 years). Donor sources were: 2 6/6 HLA-matched sibling bone marrow (BM), 2 6/6 HLA-matched UCB, and 3 4/6 unrelated UCB. Mean cell dose was 12.02+/-13.0 × 107 TNC/kg and 1.03+/-1.66 × 106 CD34/kg. Patients received tacrolimus and mycophenolate mofetil as GVHD prophylaxis and phenytoin as seizure prophylaxis for 180 days post SCT. Of 5 patients evaluable for myeloid recovery (1 did not nadir, 1 too early), mean neutrophil and platelet recovery was on day +30 ± 7(n = 5) and day +60 ± 18(n = 5), respectively. One patient had primary graft failure at day +60 post SCT (Bu steady state concentration (Css) 552 ng/ml). Busulfan pharmakokinetics were then changed to maintain Css between 600–900 ng/ml. Mean whole blood donor chimerism on days +30, +60, and +100 was 49%±33(n = 6), 61%±32(n = 5), and 82%±13(n = 4), respectively. More recently, erythroid engraftment (CD71) is being determined. Mean CD71 chimerism on days +30 and +60 was 55.3%±41(n = 3) and 61.1%±17.5(n = 3), respectively. Hb electrophoresis was done on all patients with mean %HbS levels of 1.80 ± 1.02(n = 5) and 7.46 ± 9.88(n = 5) on days +30 and +100, respectively. Grades II-IV acute GVHD was seen in 3/7 patients(42%). Chronic extensive GVHD was seen in 1/5(20%) patients. All patients are alive with the longest follow up being 1120 days post SCT. In summary, NAC and AlloSCT in patients with SCD using both related and unrelated donors has been shown to be well tolerated and effective in inducing a high degree of mixed donor chimerism.

Source: Transplantation and Cellular Therapy

DOI: 10.1016/j.bbmt.2007.12.230