Autologous Stem Cell Transplantation with Bendaeam (Bendamustine, Etoposide, Cytarabine, Melphalan) As Conditioning Regimen for Non-Hodgkin’s Lymphoma and Hodgkin’s Lymphoma

Background: High dose chemotherapy followed by autologous stem cell transplantation (ASCT) remain standard of care in patients with relapsed non Hodgkin’s lymphoma (NHL) and Hodgkin’s lymphoma (HL). This regimen is also proposed as consolidation therapy in patients with poor prognosis aggressive NHL and mantle cell lymphoma in first complete remission (CR). BEAM (BCNU, etoposide, cytarabine, melphalan) is the standard protocol chemotherapy used as conditioning regimen. A few previous studies with Bendamustine replacing BCNU have been reported with promising results. BendaEAM seems to show less toxicity and might improve results in relapsed Hodgkin/non-Hodgkin’s lymphoma (R-HL/NHL) patients.

Method: From January 2014 to July 2014, patients with NHL and HL were enrolled in this study. Previous therapy consisted in Rituximab (R)-CHOP (cyclophosphamide, doxorubicine, vincristine, prednisone) for all NHL patients transplanted in first CR. Patients with relapsed NHL and HL received high-dose cytarabine based salvage regimen. No patient presented significative comorbidity. Functional pulmonary test and cardiac evaluation were performed for all patients. with the conditioning regimen consisted in Bendamustine on day -7 and -6 (200 mg/m²/d), cytarabine daily from day -5 to day -2 (200 mg/m²/d), etoposide daily from day -5 to day -2 (200 mg/m²/d) and melphalan on day -1 (140 mg/m²). Autologous stem cells were infused on day 0. Prophylactic use of colony-stimulating factors was not allowed except for patients with less than 2x10⁶ in the apheresis product. Patients received antimicrobial prophylaxis with oral fungizone. Red cells and platelets transfusions were administered to maintain hemoglobin level >8g/dl and a platelet count (PLT) >10x10⁹/l. Broad spectrum antibiotics were delivered when fever developed.

Results: There were 25 patients: 10 patients with diffuse large-B cell lymphoma and high international prognostic score (IPI) score in first CR, 5 patients with relapsed NHL or HL, 4 patients with mantle cell lymphoma in first CR, 5 patients with relapsed follicular lymphoma, and 1 patient with peripheral T cell lymphoma. A median number of 4,1x10⁶ (range: 1.5-8.1) CD34 cells/kg was infused. All patients fully engrafted after a median time of 19.5 days (range: 14-24). Median times to PLT>20x10⁹/l and PLT>50x10⁹/l were 20 days (range: 16-52) and 22 days (range: 18-52) respectively. All patients experienced grade 3-4 fever with a documented infection in 9 cases Five patients were admitted in intensive care unit for septic shock and one patient died. One patient presented a total resolutive grade 4 renal failure. Three patients (12%) developed grade 3 cardiotoxicity (atrial fibrillation). No pulmonary toxicity was observed. Median time to hospital discharge was 23 days (range: 18-77). With a median follow-up of 2 months (range: 1-6) 24 patients are alive in CR.

Conclusion: BendaEAM as conditioning regimen followed by ASCT is feasible in patients with NHL and HL. Toxicity of this chemotherapy is acceptable and seems comparable to that observed with the standard BEAM regimen (data will be presented). While the follow-up remains short, results are encouraging in patients with NHL or HL, as well as in first CR or subsequent CR.

Thus, the use of bendamustine in lymphoma conditioning regimen can be recommended on the basis of its high anti-lymphoma activity, but also according to the safety of the drug with a lower pulmonary toxicity.