Favorable Preliminary Results Using TLI/ATG-Based Pre-Transplant Conditioning for Matched Unrelated Donor Allogeneic Hematopoietic Cell Transplantation in Pediatric Severe Aplastic Anemia

A. Pillai, C. Hartford, C. Wang, D. Pei, J. Yang, A. Srinivasan, B. Triplett, M. Dallas, W. Leung
2011 Biology of Blood and Marrow Transplantation  
3). Fifteen patients had improvement in, or correction of, their underlying PIDD. Although these results are preliminary, our early experience suggests that outcomes can be improved in high-risk patients with PIDD by using a modified nonmyeloablative conditioning regimen and by selecting marrow as the source of hematopoietic cells. We observed stable donor engraftment in most cases, an acceptable TRM, a low incidence of chronic GVHD, and correction of underlying disease processes. Many patients
more » ... lack an HLA-matched donor. We evaluated whether the use of a fixed dose of CD3 1 cells with megadoses of CD34 1 cells from Haplocompatible related donors (HRDs) would be associated with good outcomes in children. From 2002 to 2010, we performed a prospective Phase II trial utilizing the CliniMACs (Miltenyi Biotec, Bisley, UK) system to perform CD34 1 cell selection of PBSC from HRDs in 21 pediatric patients (median age 6.4 yrs, range 1.4-20.5 yrs). 15 patients had a hematologic malignancy (AML/MDS, n 5 9; ALL, n 5 4; CML, n 5 1; JMML, n 1), 6 patients had a non-malignant condition (Bone Marrow Failure, n 5 3; HLH, n 3). Conditioning was TBI 1200 cGy (200 cGy bid on Days -9 to -7), Thiotepa (5 mg/kg/dose bid on Day -6), Fludarabine (40 mg/m 2 /dose on Days -6 to -2), and Thymoglobulin (0.5 mg/kg on Day -5, 1 mg/kg on Days -4 to -2). Patients received a median of 20 Â 10 6 /kg (range: 11-33 Â 10 6 /kg) CD34 1 cells with 3 Â 10 4 /kg CD3 1 cells/kg. Events were: graft failure, relapse, and TRM. Statistics were performed using SPSS 16.0. EFS was estimated using the Kaplan-Meier method. Engraftment occurred in all but 2 patients (90%; 95% CI, 70-99%), both with AML/MDS. Relapse occurred in 3 of 15 patients (20%; 95% CI, 6-46%) at a median of 3.7 months (range: 1.3-12.4 months) post-HCT. All 5 patients eventually expired, despite 2 nd HRD HCT for 4 patients. One or more planned DLI (3 Â 10 4 CD3 1 cells/kg) were administered to 11 patients to enhance immunologic recovery. Grade I-II aGVHD was seen in 9 of 19 evaluable patients (47%; 95% CI, 27-68%). There was no Grade III-IV aGVHD. cGVHD was seen in 6 of 17 evaluable patients (35%; 95% CI, 17-59%). Infections (Sepsis & Mucor) resulted in the death of 2 patients (10%; 95% CI, 1-30%) at 11 & 22 months post-HCT; both were being treated for cGVHD. For all patients, the est. 2-year EFS was 61% (95% CI, 49-73%). Patients with non-malignant diseases had an est. 2-year EFS of 100% (95% CI, 56-100%). Patients with malignancy in remission (n 9) had an est. 2-year EFS of 64% (95% CI, 47-80%), while those not in remission (n 6) had an est. 2-year EFS of only 22% (95% CI, 3-41%). Median follow-up of survivors was 34 months (range: 3-103 months). Megadose CD34 1 cells with a fixed CD3 1 cell dose from HRDs resulted in outcomes similar to those seen with other alternativedonor stem cell sources. For pediatric patients with non-malignant diseases or those transplanted in remission, outcomes were excellent.
doi:10.1016/j.bbmt.2010.12.091 fatcat:xwhngco6jnhjnczjpu4y65xdhm