FluBup-ATG-TBI for High-Risk or Advanced Adult ALL in Remission: A Retrospective Review of a Mature Cohort.

Hematopoietic stem cell transplantation (HSCT) is routinely offered to suitable candidates with high-risk or advanced acute lymphoblastic leukemia. In this report we describe our experience with a novel conditioning regimen, previously reported to confer low TRM and high OS in AML, in this population.

Between 05/2000 and 06/2008 44 patients with high-risk (either adverse cytogenetics, age > 35 or high WBC at diagnosis) or advanced (>CR1) ALL received HSCT after myeloablative conditioning using Fludarabine 50 mg/m2 days -6 to -2, Busulfan 3.2 mg/kg days -5 to -2, and TBI 2 Gy x 2 doses. GVHD prophylaxis was with rabbit ATG 0.5 mg/kg day -2, then 2 mg/kg days -1 and 0, CyA (tapered on day +56) and short-course methotrexate. All patients were in remission at the time of transplant. Imatinib mesylate (Gleevec) was not used routinely before or after transplant for patients with BCR-Abl+ ALL. Median (range) follow-up of surviving patients is 4.3 (1.0 – 9.0) years. All patients were followed for at least 1 year after BCT.

The cohort consists of 32 patients with high-risk (median age 40 (19-64) years) and 12 patients with advanced (median age 25 (19-65) years) disease who received bone marrow (n=5), G-CSF mobilized blood stem cells (n=38) or umbilical cord blood stem cells (n=1) from 25 related (21 fully-matched) or 19 unrelated (16 fully-matched) donors. Median times to neutrophil and platelet engraftment were 14 (11-28) days and 18 (9-105) days, respectively. Five patients did not require platelet transfusion. Cumulative incidences of grade II-IV and grade III-IV acute GVHD were 53.2% (95% CI 36.3%-67.5%) and 20.6% (95% CI 3.5%-47.6%), respectively. Chronic GVHD complicated 55% (95% CI 38.4%-68.8%) of transplants. Six patients (13.6%) died in remission before day +100. Event-free and overall survivals at 5 years were 56.7% (95% CI 39.1%-71.0%) and 66.0% (95% CI 48.8%-78.6%), respectively. Nine patients (20%) died in remission, 6 (14%) died after relapse and two patients remain alive following second transplants for relapsed disease. Five of 11 patients age > 50, 8/12 patients with advanced disease and 13/23 patients with adverse-risk cytogenetics remain alive.

We found encouraging results with FluBup-ATG-TBI in a cohort of patients with advanced or high-risk ALL. These results warrant comparison with other conditioning regimens in a randomized, multi-center study.

Daly:Hoffmann-Laroche: Advisory Board, Honoraria. Stewart:Hoffmann La Roche: Advisory Board, Honoraria, Research Funding.