787 Multiple cycles of aggressive chemotherapy for relapsed lymphoma

Abstract

Patients with non-Hodgkin's lymphoma and advanced Hodgkin's disease who relapse after first line therapy have a poor prognosis. Around 30–40% of patients with disease sensitive to salvage chemotherapy achieve long term survival after subsequent high dose chemotherapy (HDCT) and autologous bone marrow transplantation (ABMT). In addition, for patients undergoing HDCT, the use of peripheral blood progenitor cells (PBPC) results in faster neutrophil and platelet recovery compared with bone marrow. Based on the premise that a single cycle of HDCT may be suboptimal, we piloted a regimen combining 5 days of infusional ara-C and etoposide with bolus doses of cyclophosphamide and methotrexate and high dose oral dexamethasone (MADEC) as a salvage therapy for patients with relapsed lymphoma. Following MADEC all patients received granulocyte colony stimulating factor to assist in mobilisation of PBPC, and to reduce the incidence of febrile neutropenia. Twenty-five patients with relapsed lymphoma (19 with intermediate grade non-Hodgkin's lymphoma, 6 with Hodgkin's disease) received a total of 45 cycles of MADEC. All had demonstrated response to prior induction chemotherapy (22 CR, 3 PR) with median duration of response of 6 months (1–60 mos). There was one toxic death. The MADEC regimen was intensely myelosuppressive. All patients had nadir granulocyte counts of > 0.5 × 109/l, resulting in hospitalisation for febrile neutropenia after 35 of 45 cycles. Platelet and packed cell transfusions were required after the majority of cycles. Non-haematological toxicity was mainly mucositis and was generally mild. Of 24 evaluable patients 8 achieved CR after MADEC and 10 achieved PR (6 pts with residual masses had gallium scans, 5 were negative). Patients responding following cycle 1 underwent leukapheresis after the neutrophil nadir. Median number of leukaphereses was 2 (1–4). Median number of CD34+ cells mobilised was 2.75 × 106/kg (0.5–22.8 × 106/kg) and median number of CFU-GM was 68.4 × 104/kg (0.5–697.5 × 104/kg). In responding patients a second course ofMADEC was given to achieve maximal reduction of disease bulk prior to transplantation. Sixteen patients proceeded to HDCT with PBPC support. All patients engrafted successfully with median days to ANC Conclusion The MADEC regimen was useful for identifying patients with chemosensitive disease who may benefit from HDCT and for maximal reduction of disease bulk prior to the procedure. Combination with G-CSF resulted in mobilisation of adequate numbers of PBPC to support engraftment after HDCT The therapeutic benefits of this regimen relative to less intensive regimens prior to transplant warrants evaluation.