Work

73: Low rates of toxicity and long-term responses after bu/flu/ATG RIC allogeneic transplantation in very high risk pediatric patients ineligible for myelablative therapy

Year: 2007

Type: article

Abstract: The role of reduced intensity conditioning (RIC) regimens in pediatric pts is unclear. To define the feasibility and toxicity of this approach using multiple stem cell sources in pediatric pts ineligible for myeloablative transplant, we conducted a trial at 25 centers participating in the Pediatric Blood and Marrow Transplant Consortium (PBMTC). Thirty two pediatric pts (age 2-20yrs, med 12) have been enrolled to date with the following stem cell sources: 7 related donor (RD) BM (2 mismatched); 5 RD-PBSC; 9 unrelated donor (UD) BM; 4UD-PBSC; 7 UD-CB. Qualifying indications included a previous allogenic (n=15) or autologous (n=4) transplant, severe organ toxicity (n=5), invasive fungal infection (n=2), and other comorbidities, (n= 6 pts, 4 with Down syndrome). Diagnoses included ALL (4 CR2; 9 CR3), AML (6 CR2; 3 CR3; 1 secondary), MLL (1 CR3), HD (2 CR3), B-NHL (1 PR3), MDS (2 RA; 1 secondary RA; 1 RAEB in CR1), and JMML (1 PR3). Patients received busulfan 0.8mg/kg/dose IV × 8 doses (target AUC 900-1100 uM/min), fludarabine 30mg/m2/d × 6 days, and thymoglobulin, 2.5 mg/m2/d × 1 day for RD and × 4 days for UD and UCB. Two pts rejected their grafts, one after a mismatched RD-BM, and a second after UD-BM. Two pts died prior to day 100 due to toxicity (6%) and the overall NRM is 16%. Acute GVHD (grade I-II) occurred in 3/25 (12%, no grade III-IV) and chronic GVHD occurred in 4/18 (22%) evaluable pts. Median follow up is 12 months (range 1-35 m). Of 30 pts >30 days out from transplant, 10 pts relapsed. Two year EFS and OS are 49% (SE 9.8) and 49% (SE 11%), respectively. Two relapsed pts are alive at 5 and 1 months after a second transplant and DLI, respectively. One patient who rejected received a second RIC, engrafted, and is alive with cGVHD. Of the 8 pts surviving more than one year from transplant, 4 had AML/MDS (2 in CR2; 1 secondary AML; 1 secondary MDS), 3 had ALL (1 in CR2; 2 in CR3,), and 1 had HD in CR3. In conclusion, RIC using bu/flu/ATG in a large cooperative group setting leads to engraftment in >90% of very high risk pediatric pts using a variety of stem cell sources. In spite of significant prior therapy and comorbidities in this cohort, rates of NRM and GVHD are low. Prolonged relapse free survival has occurred not only in pts with myeloid disease as expected, but also in pts with ALL and lymphoma. Flu/bu/ATG is a promising therapeutic approach for pediatric pts otherwise ineligible for myeloablative transplant.

Source: Transplantation and Cellular Therapy

DOI: 10.1016/j.bbmt.2006.12.076