Busulfan-Containing Conditioning Regimens in Allogeneic Hematopoietic Stem-Cell Transplantation for Acute Lymphoblastic Leukemia: Single Tertiary Center Experience in Taiwan

Abstract

The allogeneic hematopoietic stem-cell transplantation (allo-HSCT) is viewed as the ultimate cure for acute lymphoblastic leukemia (ALL). An essential component of allo-HSCT is the conditioning regimen administered before the hematopoietic stem-cell infusion. This study is aimed to compare outcomes of ALL patients receiving either a busulfan with cyclophosphamide (BuCy) or a total body irradiation(TBI)-based regimen. We retrospectively analyzed data from National Taiwan University Hospital institute registry. We enrolled 224 adult patients with ALL who received allo-HSCT between 1997 and 2016 and compared outcomes of patients receiving either a BuCy-based or a TBI-based regimen. There were more B-cell ALL than T-cell ALL (67.8% vs 32.2%). A total of 41 patients (22.5%) carried the Philadelphia chromosome (Ph) while 38 patients (20.9%) carried complex karyotype. Before the allo-HSCT, 164 (73.2%) patients achieved first or late complete remission (CR). The main source of stem-cell was from peripheral blood (71%), followed by bone marrow (22.3%). Siblings comprised 54.9% of the donors. A total of 141 patients (63%) received BuCy-based conditioning, either myeloablative (MA) or reduced intensity stem cell transplantation (RIST) and 83 patients (37%) received TBI-based regimen. The mean dose of stem cell was 4.96 ± 2.42 × 106/Kg CD34+ cells. We use cyclosporine and mycophenolate mofetil for prophylaxis of graft-versus-host disease (GvHD). In results, patients received BuCy-based regimen performed as well as TBI-based group in terms of 5-year overall survival (47.5% vs 37.3%, p=0.115). As to 5-year relapse-free survival (RFS), BuCy group had slightly better result, especially the group received myeloablative conditioning (MA, Bu-based vs. MA, TBI-based, p=0.059), albeit the p value didni¦t reach significance, the curves went on departing ways. In this study, all regimen groups yielded similar treatment-related mortality (TRM), (MA, Bu-based vs RIST, Bu-based vs MA, TBI-based: 17% vs 10.9% vs 21.7%, p=0.308) and incidences of grade 3-4 acute GvHD at day+100, (p=0.445). Further, in patients with extramedullary disease, there was no difference among groups; and interestingly, BuCy group with MA conditioning seemed to yield better result than TBI group (p=0.072). By multi-variate analysis, disease status before allo-HSCT is the only risk factor impacting OS and RFS. In conclusion, patients received BuCy-based regimen or TBI-based regimen as conditioning had similar results in terms of OS, RFS, TRM, and GvHD.