Comparison of Fludarabine, Intravenous Busulfan, and Total Body Irradiation (FluBuTBI) to BEAM As Conditioning Regimens for Autologous Peripheral Blood Stem Cell Transplantation in Non-Hodgkins Lymphoma

Objective:  To compare the outcome of patients with Non-Hodgkins Lymphoma undergoing autologous peripheral blood stem cell transplantation (PBSCT) conditioned with FluBuTBI or BEAM (BCNU, Etoposide, Cytarabine, and Melphalan) at our institution.

Patients and Methods:  We conducted a retrospective analysis of patients (n=81) who underwent autologous PBSCT at our institution and were conditioned with BEAM (n=40) or FluBuTBI (n=41) between January 2006 and January 2013. Recipients were classified according to CIBMTR criteria and those conditioned with BEAM were low risk (n=14) and intermediate risk (n=26). Recipients conditioned with FluBuTBI were low risk (n=10), intermediate risk (n=27) and high risk (n=4).  Median age of patients in the BEAM group was 57.2 years compared to 59.6 years for FluBuTBI. At the time of transplantation, 25 of 40 patients who received BEAM were in complete remission (62.5%) compared to 21 of 41 patients (51.2%) for FluBuTBI. Median time of follow up was 57 months for BEAM and 30.2 months for FluBuTBI.

FluBuTBI consisted of intravenous (IV) Fludarabine 50 mg/m²/day infused over 1 hour on days -6 through -2, IV Busulfan 3.2 mg/kg/day on days -5 through -2 (infusion rate 80 mg/hour) and TBI 200 cGy on days -2 and -1. BEAM regimen consisted of IV BCNU 300 mg/m² infused over 1 hr on day -5, Etoposide 200 mg/m²/day over 3 hours on days -5 through -2, Cytarabine 200 mg/m²/day over 1 hour every 12 hours on days -5 through -2, and Melphalan 140 mg/m² over 1 hr on day -1. Diagnoses were transformed follicular lymphoma (n=1), composite lymphoma (n=1), CLL (n=1), anaplastic large cell lymphoma (n=2), B-cell lymphoma NOS (n=3), Burkitt’s lymphoma (n=3), peripheral T-cell lymphoma (n=5), follicular lymphoma (n=16), mantle cell lymphoma (n=23), diffuse large B-cell lymphoma (n= 26).

Results:  Overall survival (OS) at 3 years for the FluBuTBI group was 76.2% compared to BEAM at 57.5%. Cumulative incidence of disease progression at 3 years was 24.5% for FluBuTBI compared to 45% for BEAM group (p=0.039).   Relapse related mortality (RRM) at 3 years for FluBUTBI was 8.7% compared to 32.4% for the BEAM group (p=0.012).  Treatment related mortality was observed in 2.5% (n=1) in the BEAM group while none in the FluBuTBI group.   Treatment related MDS/AML occurred in 2.4% (n=1) in FluBUTBI compared to 7.5% (n=3) in the BEAM group. Grade 3-4 mucositis was seen in 14.6% (n=6) in the FluBuTBI group while not observed in the BEAM group.

Conclusion:  Our institutional data showed better OS and less RRM in the FluBuTBI group compared to BEAM as conditioning regimen for Non-Hodgkins Lymphoma undergoing Autologous PSCT.  This difference was present despite older and higher risk patients in the FluBuTBI group. Mucositis was more frequent in the FluBuTBI group. Conditioning with FluBuTBI is a safe and effective alternative to BEAM for autologous PBSCT which needs to be validated by randomized prospective studies.