Work

341: Reduced-intensity allogeneic umbilical cord blood transplantation (RI-UCBT) in pediatric recipients with malignant and non-malignant diseases

Year: 2007

Type: article

Abstract: There is a significant amount of morbidity and mortality following myeloablative UCBT, in part secondary to a log less TNC/CD34+ cells/kg infused compared to matched BM or PBSC (Cairo et al, Blood, 1997). RI conditioning followed by BM or matched PBSC may potentially reduce the incidence of TRM and the late effects associated with myeloablative regimens without increasing the risk of graft failure or relapse (Satwani/Cairo, BBMT, 2005). Since UCB has a log less cells, it remains to be determined whether RI conditioning will be as successful when combined with UCBT. We currently report the results of RI-UCBT in 21 pediatric pts, median age 7.5 years (0.33-20 yrs). HLA match: 4/6 -13, 5/6-5, 6/6-3. Malignant diseases n=14, Hodgkin’s disease n=5 (CR2-2, SD -1 and PD-2), NHL n=2 (ALCL-PR1 and DLBCL-SD), CML (CP-1), AML n=3 (CR1-2and CR2-1), MDS n=3 and non-malignant diseases n=7, HLH-2, WAS-1, B-Thal-1, SAA -1, SCID’s-2. RI conditioning consisted of fludarabine (150-180mg/m2)with either busulfan (8mg/kg)+ATG (n=16) or cyclophosphamide+ATG±etoposide (n=5). GHVD prophylaxis consisted of FK-506 and MMF (Osunkwo/Cairo, BBMT, 2004). The median TNC/ kg was 3.58×107(0.92-22.61) and the median CD34+ cell dose/kg was 2.54×105(0.34- 9.57). The median time for neutrophil and platelet engraftment was 17.5 days (1-47) and 52 days (6-170), respectively. There were 6 primary graft failures (1 CML, 1 b-Thal, 2 HLH, 1 MDS, and 1 AML), 4/6 who were regrafted with myeloablative conditioning followed by a UCBT achieved100% engraftment. In the remainder 14 evaluable patients the donor chimerism at 30 and 180 days was 74± 20% and 90± 10%, respectively. The probability of developing grade II-IV aGVHD and cGVHD was 28.6% and 16.7%, respectively. Incidence of TRM was 14%. The 2yr OS in all patients was 59.8% (CL95: 37.9-81.6). The 2yr OS for patients with average risk malignancy was 77.8% (CL95: 50.6-100) and poor risk malignancy was 20.2% (CL95: 0-55.1). These preliminary results indicate that despite a log less TNC/CD34+ cells/kg infused compared to matched BM or PBSC, RI-UCBT may result in rapid hematopoietic reconstitution while decreasing TRM compared to myeloablative UCBT and be associated with high donor chimerism. Patients with some diseases such as CML, b-Thal, and HLH may require increased intensity of conditioning. Further follow-up is required to evaluate long-term effects in pediatric patients following RI-UCBT.

Source: Transplantation and Cellular Therapy

DOI: 10.1016/j.bbmt.2006.12.346