Reduced Intensity Conditioning (RIC) Allogeneic Stem Cell Transplantation (allo-SCT) for Patients with Acute Lymphoblastic Leukemia (ALL): A Survey from the European Group for Blood and Marrow Transplantation (EBMT).

The role of RIC allo-SCT for adult patients with ALL is still under considerable debate. While the use of such so-called nonmyeloabaltive or RIC regimens has emerged as an attractive modality to decrease transplant-related toxicity, it is still unclear whether such regimens are associated with a graft-vs.-leukemia (GVL) effect in adult ALL. This report describes the results of 91 adult ALL patients (62 M and 29 F) treated in different centers affiliated with the EBMT. Median age was 40 y. (range, 17–66). Twenty nine (32%) patients were transplanted in first complete remission (CR), 28 (31%) beyond first CR, and 34 (37%) in advanced disease. In this cohort, 39 patients (51%) had a Ph+ or t (4;11) ALL. The majority of patients received a PBSC graft (78%) from an HLA-matched sibling donor (n=62; 68%). The RIC regimen included Fludarabine (80%) associated to low dose TBI in 22 patients (24%), and/or low dose Bussulfan (<8mg/kg). ATG was used in 29 patients (33%), mainly in unrelated HSCT. With a median follow-up of 34 months (range, 7–76), the incidences of grade II-IV and grade III-IV acute GVHD were 35% and 13% respectively. At 2 years, chronic GVHD occurred in 49% of patients. Cumulative incidence of transplant-related mortality at 3 years (TRM; 11 fatal infections, 5 refractory GVHD, 6 other) was 24% (15% in patients transplanted in first CR). Cumulative incidence of relapse at 3 years was 58%+/−5 in this high risk group. Three years leukemia-free survival (LFS) was 18% in the whole study group, with this being significantly higher (34%) in patients transplanted in first CR. Patients transplanted in advanced refractory disease had the worst LFS (5%). In multivariate analysis, disease status at time of allo-SCT (first CR vs. other) was the strongest factor associated with an improved LFS (P=0.04; RR=2.1; 95%CI, 1.02–4.20).

The results of this retrospective registry based study suggest that RIC allo-SCT for adult ALL may represent a valid therapeutic option when a conventional standard conditioning is not possible. Of note, results obtained in patients transplanted in first CR (LFS and TRM) compare favorably with previous results achieved after standard myeloablative allo-SCT, warranting further investigations in this subgroup. Also, better understanding of the putative GVL effect in adult ALL, in addition to designing maintenance strategies (imatinib in Ph+ ALL for eg.) after RIC allo-SCT, may further improve the outcome of adult ALL.