Intravenous Busulfan (IV Bu)-Based Conditioning Regimen Before Allogeneic Stem Cell Transplantation (allo-SCT) for Adults with Acute Lymphoid Leukemia (ALL): A Aurvey From the Acute Leukemia Working Party of EBMT

Abstract 3005

Allo-SCT is an effective postremission therapy when compared to chemotherapy for adult patients with ALL. However, some studies suggested that the benefits from allo-SCT antileukemia effects are offset from the high non-relapse mortality (NRM), especially when using high dose TBI-based myeloablative conditioning. At present, it is well established that IV BU is as potent in inducing apoptosis of primary ALL cells as it is in AML. Marrow ablative or nonmyeloablative doses of IV BU were shown to be well tolerated in older adults when used as part of the conditioning regimen. With this background, this survey performed between 2000 and 2010, aimed to assess the outcome of 467 adult patients with ALL who received IV Bu-based conditioning regimen (without TBI) prior to allo-SCT.

In this series, the median age was 37 years (range, 18–71) and the median year of allo-SCT was 2008. A B-lineage ALL was diagnosed in 317 cases (68%). 274 patients (59%) received allo-SCT from an HLA-matched related donor, while 168 patients (36%) received an HLA-matched unrelated graft (at least 6/6 match), and 25 (5%) received an HLA-mismatched graft. G-CSF-mobilized PBSCs were used as stem cell source in 387 cases (83%), and bone marrow in the remaining 80 cases (17%). At time of allo-SCT, 301 patients (64%) were in first CR, 88 patients (19%) in second CR and 78 cases (17%) in more advanced phases. As per inclusion criteria, all patients from this series received a conditioning regimen combining IV Bu and other chemotherapeutic drugs. 359 patients (77%) received a standard myeloablative conditioning (MAC) regimen (252 cases consisting of IV Bu 3.2 mg/Kg/day for 4 days and Cy; 77 cases IV Bu and Fludarabine, and 30 cases of IV Bu and other drugs). The remaining patients (23%) received a so-called reduced-intensity conditioning (RIC) consisting of nonmyeloablative doses of IV Bu (total dose ≤ 9.6 mg/Kg) and Fludarabine in the majority of cases (89%).

In this series, 96% of patients achieved neutrophil engraftment at a median time of 15 days after allo-SCT. The incidences of grade II and grade III-IV acute GVHD were 18% and 10%, respectively. When considering patients in first CR who received transplant from an HLA-identical sibling, the cumulative incidence of NRM was 14±3% at 2 years. NRM was 29±8% at 2 years in patients transplanted in second CR from an HLA-identical sibling. In the unrelated transplant group, NRM incidences were 31±6% at 2 years for patients transplanted in first CR and 41±8% for patients transplanted in second CR. The cumulative incidences of relapse were 38±4% at 2 years for patients transplanted in first CR and 41±7% for patients transplanted in second CR using a matched related donor. In the unrelated transplant group, relapse rates were 31±5% at 2 years for patients transplanted in first CR and 44±8% for patients transplanted in second CR. With a median follow-up of 12 months (range, 1–88) after allo-SCT, leukemia-free survival (LFS) was 48±5% at 2 years for patients transplanted in first CR using an HLA-identical sibling. LFS was 30±8% at 2 years for patients transplanted in second CR using an HLA-identical sibling. In the unrelated transplant group, LFS rates were 38±6% at 2 years for patients transplanted in first CR and 15±6% for patients transplanted in second CR.

In summary, results from this survey suggest that the use of IV Bu-based conditioning regimen may represent a valid option for the conditioning of adult ALL patients prior to allo-SCT. The use of IV-Bu-based RIC allowed a significant number of ALL patients not eligible to MAC to proceed to allo-SCT. Outcomes (NRM, LFS and relapse incidence) achieved after such regimens (especially in patients in first CR) compare favourably to figures from historical series using TBI-based conditioning, warranting a prospective randomized trial.