Fludarabine, Intravenous Busulfan, and Total Body Irradiation (FluBuTBI) Conditioning for Allogeneic Peripheral Blood Stem Cell Transplantation the Western Pennsylvania Cancer Institute Experience

Introduction: Allogeneic hematopoietic stem cell transplantation (HSCT) utilizing myeloablative conditioning is associated with high treatment-related mortality (TRM). In an effort to reduce TRM yet maintain myeloablative efficacy we employed Fludarabine, intravenous Busulfan and total body irradiation 400 cGy  (Flu/Bu/TBI). We present our single institution experience with this regimen.

Method:  We conducted a retrospective analysis of 89 patients who underwent Flu/BU/TBI conditioning regimen prior to allogeneic HSCT at our institution between the years 2007 and 2012. Flu/Bu/TBI consisted of intravenous(IV) Fludarabine 50 mg/m² infused over 30 minutes for 5 days on days -6 through day -2 and IV Busulfan 3.2 mg/kg/day on days -5 and –2 (infusion rate 80 mg/kg/hr) and TBI of 400cGY administered in divided doses on day -1 and 0. All patients received Thymoglobulin at a dose of 4.5mg/kg or 6 mg/kg administered in divided doses on days -2, -1, and 0. Post transplantation graft versus host disease (GVHD) prophylaxis consisted of tacrolimus and mycophenolate mofetil. Diagnoses included Acute Myeloid Leukemia (AML) (n=37), Acute Lymphoblastic Leukemia (ALL) (n=19), Myelodysplastic Syndrome (MDS) (n=10), Non-Hodgkins Lymphoma (NHL) (n=12), and others (n=11). The median age of entire cohort was 50 years (range 21-68). CIBMTR risk stratification of the patients revealed high risk in the majority with only 30 (34%) patients achieving CR1 or CR2 status prior to transplant. Fourty-five (51%) patients had a comorbidity score of ≥2.

Results: 1 and 3 year overall survival (OS) for the entire cohort was 46.9% and 34.6%. OS in patients in CR when compared to those not in CR, was significantly better at 1 and 3 years at 73% and 55% compared to 34% and 24%( p<0.001). OS in patients who achieved CR and had low CMS was 78% at 1 year.  Cumulative incidence of progression and relapse free survival for the entire cohort was 60.7% and 55.5% at 1 and 3 years. In patients who achieved CR, relapse free survival was significant at 81% and 68% at 1 and 3 years (p<0.039). Incidence of grade 2 acute GVHD was 19% and grades 3-4 was12.3%. Cumulative incidence of treatment related mortality (TRM) for the entire cohort at 3 years was 30.4%, but for patients who achieved CR, the TRM was significantly lower at 13.3% (p<0.05)

Conclusion: Our data shows that FluBuTBI conditioning is a well-tolerated conditioning regimen, which can provide adequate cytoreduction while maintaining acceptable TRM. The results are particularly encouraging for patients who achieve remission prior to transplant and those with low comorbidity score. In agreement with previous publications, our findings suggest that FluBuTBI is a reasonable alternative to the traditionally used myeloablative regimens.