Reduced Intensity Fludarabine and Intravenous Busulfan (FB2) for Allogeneic Peripheral Blood Stem Cell Transplantation

Objective:To demonstrate the efficacy and safety of a reduced intensity conditioning (RIC) regimen comprising Fludarabine and intravenous Busulfan (FB2) in patients undergoing allogeneic peripheral blood stem cell transplantation (PBSCT) for hematological disorders.

Patients and Methods: We conducted a retrospective analysis of 42 patients who underwent RIC prior to PBSCT at our institution between the years 2009 and 2012 inclusive. FB2 consisted of Fludarabine 30 mg/m²/day infused over 30 minutes for 5 days on days -6 through -2 and Busulfan 3.2 mg/kg/day on days -3 and -2 (infusion rate 80 mg/kg/hour). All patients received Thymoglobulin at a total dose of 4.5 mg/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 (n=3), Acute Lymphoblastic Leukemia (n=2), Myelodysplastic Syndrome (n=10), Severe Aplastic Anemia (n=5), Chronic Lymphocytic Lymphoma (n=8), Non-Hodgkin’s Lymphoma (n=8), Hodgkin Lymphoma (n=4) and Myeloproliferative Disorder (n=2). The median age of the recipients was 56 years with 18 patients (44%) aged > 60 years. Only 9 patients (21%) were in complete remission (CR) at the time of HSCT and 19 (45%) were considered to have high-risk disease by CIBMTR criteria. The co-morbidity index was 3 or more in 19 recipients (45%).

Results:At a median follow up of 15 months, overall survival (OS) for the entire cohort was 62%. OS for patients undergoing PBSCT in CR versus not in CR was 89% and 55% respectively. OS was similar in recipients undergoing PBSCT from matched unrelated (n=29) or matched related (n=13) donors. Median engraftment time for neutrophils (ANC >500) and platelets (>20K) was 18 and 17 days, respectively. Acute GVHD grade 2 developed in 15 (36%) of recipients, grade 3 in 2 (5%) and grade 4 in 2 (5%). The cumulative incidence of relapse was 37% (n=13). There were no graft failures and treatment related mortality (TRM) was 2% (n=1).  At one year following PBSCT, 10 patients (24%) had extensive chronic GVHD and 19 patients (45%) required continuation of immunosuppressants. All patients with SAA (n=5) are alive, engrafted and did not develop grade 3 or 4 acute GVHD.

CONCLUSION: Our preliminary data demonstrates low toxicity and favorable outcome in older patients with elevated co-morbidity score and high-risk disease using the FB2 regimen. The efficacy, tolerability and excellent outcome of FB2 warrants further study in recipients with SAA.