Post-Transplant Cyclophosphamide Is Feasible and Reduces Acute GvHD in Pediatric UCB Transplantation
Oscar Ramirez, Viviana Lotero, Maria Ximena Castro, Carlos Andres Portilla, Margarita Quintero
2013
Biology of Blood and Marrow Transplantation
matched sibling bone marrow transplantation results in approximately 85% event free survival in high-risk patients with Sickle Cell Disease (SCD) (Walters, NEJM, 2006). However, this approach is limited by 5-10% transplantrelated mortality, 5-10% primary graft failure and the late effects of Bu/CY. Alternate approaches include reduced toxicity but more immunosuppressive conditioning and the use of sibling cord blood (Geyer/Cairo, BJH, 2011 and Freed/ Cairo, BMT, 2012). Objective: To determine
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... e safety, donor chimerism and long term organ function associated with Bu 12.8-16 mg/kg, fludarabine180 mg/m 2 and alemtuzumab 54 mg/m 2 (BFA) reduced toxicity conditioning (RTC) prior to HLA-matched sibling donor transplantation in pediatric recipients with high risk SCD. Methods: Patients 21 years of age with HbSS, HbSC, HbSb + or HbSb 0 were eligible if highly symptomatic (such as 2 vaso-occlusive crises per year requiring narcotics, acute chest syndrome, stroke, retinopathy, splenic sequestration) and with an HLA-matched sibling donor. Conditioning consisted of busulfan (4mg/kg x 4d < 4 yrs and 12.8mg/ kg x 4d > 4 yrs), fludarabine (30mg/m 2 x 6d), and alemtuzumab (2mg/ m 2 x 1d, 6mg/m 2 x 2d, and 20mg/m 2 x 2d) as we have described (Styczynski/Cairo,BMT,2011). All received tacrolimus and MMF as GVHD prophylaxis as we have described (Bhatia/Cairo, BBMT, 2010). Results: 12 patients (11M:1F), median age 12 (2-19) with symptomatic SCD underwent sibling BM (n¼10) or CB (n¼2) Allogeneic Stem Cell Transplantation (AlloSCT). Median follow-up was 33 months. Median time to neutrophil and platelet engraftment for recipients of sibling BM and CB were 16 days (13-18), 18.5 days (9-43) and 39.5 days (38-41) and 74 days (73-75), respectively. The probability of grade II-IV and grade III-IV aGVHD were 16.7% and 8.3%. No patients developed cGVHD. Patients achieved mean whole-blood donor chimerism of 85, 94, 93, 93, 89 and 93% and mean erythroid (CD71) donor chimerism of 89, 89, 93, 90, 86, and 94% at days 30, 60, 100, 180, 365 and 730 post-transplant, respectively. The Kaplan-Meier probability of OS and EFS was 100% (CI 95 : 73.5-100%). Neurological, pulmonary, vascular, and splenic function were stable to improved at 2 years. Conclusions: BFA (RTC) and HLA-matched sibling bone marrow and cord blood AlloSCT in pediatric recipients results in excellent EFS, long term donor chimerism, and stable/improved organ function.
doi:10.1016/j.bbmt.2012.11.133
fatcat:eoud7tnkwnbtzfq3wufeq3jeaa