High Dose Therapy and Autologous Hematopoietic Cell Transplantation for Primary Refractory Diffuse Large Cell Non-Hodgkin’s Lymphoma.

The efficacy of high dose therapy (HDT) and autologous hematopoietic cell transplantation (AHCT) for patients with diffuse large cell non-Hodgkin’s lymphoma (NHL) who never achieve a first complete remission (CR) with conventional chemotherapy have been addressed by few published studies. We retrospectively analyzed outcomes for 43 consecutive patients with chemotherapy-sensitive primary refractory diffuse large cell NHL treated with HDT and AHCT at our center between November 1988 and January 2002. The median age at transplant was 43 years (range: 18 – 64). At diagnosis 26 patients (60%) had stage IV disease, 28 patients (65%) had extranodal involvement, and bulky disease was present in 17 patients (40%). The age-adjusted NHL international prognostic index (IPI) score was low in 4 patients (9%), low-intermediate in 18 patients (42%), high or high-intermediate in 12 patients (28%), and not available in 9 patients (21%). All patients failed to achieve a first CR following CHOP (n = 31, 72%), R-CHOP (n = 6, 14%), and other anthracycline-containing regimens (n = 6, 14%). Fourteen patients (33%) did not receive additional conventional chemotherapy before proceeding to HDT and AHCT. The remaining 29 patients (67%) received in addition between 1 – 6 cycles of salvage chemotherapy. None of the 43 patients had achieved a CR at any time point before HDT and AHCT and all patients had measurable disease at the start of the HDT regimen. The median interval from diagnosis to HDT was 8.9 months (range: 2.4 – 15.5). The HDT regimen consisted of total body irradiation, etoposide, and cyclophosphamide in 15 patients (35%); BCNU, etoposide, and cyclophosphamide in 26 patients (60%); and CCNU, etoposide, and cyclophosphamide in 2 patients (5%). All but three patients (7%) were rescued with peripheral blood stem cells mobilized with cyclophosphamide 4 gm/m2 plus G-CSF and purged with monoclonal antibodies and complement. With a median follow-up of 5.8 years (range: 0.2 – 15.8) among surviving patients, the 5-year Kaplan-Meier estimates for overall survival was 67.4% (95% CI: 52.4 – 82.4), freedom from progression was 60.1% (95% CI: 43.7 – 76.6), and event-free survival was 55.8% (95% CI: 39.2 – 72.4). Two patients with relapse post-AHCT proceeded to non-myeloablative allogeneic HCT and were censored at the time of second transplant. By univariate analyses the following characteristics were not prognostically significant for overall survival: disease stage at diagnosis (I–II versus III–IV), prior radiotherapy, age-adjusted IPI score (low versus high) in evaluable patients, and the HDT regimen (TBI versus non-TBI). These results demonstrate that HDT and AHCT is effective treatment for chemotherapy-sensitive primary refractory diffuse large cell NHL.

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