Intravenous Busulfan-Based Conditioning Regimens in Allogeneic Hematopoietic Cell Transplantation for Patients with Acute Lymphoblastic Leukemia

Introduction: Intravenous busulfan is a common component of high-dose conditioning regimens for hematopoietic cell transplantation (HCT), but it has not been well investigated in acute lymphoblastic leukemia (ALL). We retrospectively evaluated intravenous busulfan-based conditioning regimens for allogeneic HCT for adult patients with ALL.

Methods: This study included 195 patients with ALL who were in first complete remission (CR) at the time of allogeneic HCT. All patients received intravenous busulfan-based conditioning regimens: 4-day busulfan (3.2 mg/kg x 4d) plus cyclosphosphamide (n=80), 4-day busulfan plus fludarabine (n=20), and 2-day busulfan (3.2 mg/kg x 2d) plus fludarabine (n=95). Antithymocyte globulin was added at doses between 3.75 and 12 mg/kg in 104 patients.

Results: The hematopoietic cell donor was an HLA matched sibling for 82 patients, an unrelated matched volunteer for 79, and a mismatched family member for 34. All but two patients achieved an absolute neutrophil count > 500/μL on median day 12. Acute graft-versus-host disease (GVHD) occurred in 61 patients (31%): grade I in 27, grade II in 17, and grade III/V in 17, while 100 (52%) of 192 assessable patients developed chronic GVHD: mild in 17, moderate in 33, and severe in 50. After a median follow-up of 4.9 years, 72 patients relapsed, and 85 died. Twenty-five deaths were nonrelapse deaths. The probabilities of overall survival, relapse-free survival, and nonrelapse mortality at 2 years were 68%, 66%, and 10%, respectively. Post-transplant outcomes were not significantly different between 4-d busulfan and 2-d busulfan. Patients with chronic GVHD had superior outcomes compared with those without chronic GVHD, mainly because of lower incidence of relapse.

Conclusion: Our study results demonstrate that intravenous busulfan-based conditioning regimens provide effective disease control for ALL with relatively low nonrelapse mortality, and graft-versus-leukemia effects are present after allogeneic HCT for patients with ALL.