Allogeneic hematopoietic transplantation for indolent lymphomas: improved outcome with non-myeloablative versus high dose chemotherapy (HDCT) regimens

Between 1990-1999, 58 patients with indolent lymphomas who failed conventional chemotherapy (small lymphocytic= 7, follicular small cleaved= 31, follicular mixed= 15. follicular large= 5) underwent allogeneic transplantation. Median age was 45 years (range 23-67). Thirty-seven were males. Median no. of prior chemo regimens was 2 (range 1 -9). At transplantation 21 (36%) had refractory disease. 44 patients received HDCT (TBIbased=24, BEAM=20) and 14 received nonmyeloablative stem cell transplantation (NST) using fludarabine 125mg/m2 over 5 days, cyclophosphamide 2gm/m2 over 2 days ±rituximab. NST was initiated in 1996 for older patients (50 years) or others with comorbidities. The median age for NST patients was 51 (range 31-67) compared to 43 (range 43 60) for who received HDCT (P= 0.008). There was no statistical difference between the two groups in: IPI distribution, M.D. Anderson Tumor Score, or no. of prior chemo regimens received. With a median follow-up of 30 mo (range, 2-79 mo), the outcome is as follows: NST HDCT P Day 100 mortality 0.34% 0.02 GII-rVGVHD 7% 43% 0.01 Gffl-IVGVHD 0% 20.5% 0.07 Overall survival (OS) (2yrs) 73% 45% 0.05 Disease free survival (DPS) (2yrs) 73% 43% 0.02 The proportion of pts who had refractory disease at the time of transplant was higher in the HDCT than in the NST arm (43% vs 14%, P= 0.05). To circumvent this difference, we analyzed the outcome for only patients who had sensitive disease in both arms. The OS and DPS for NST were both 100% and were both 36% for HDCT (P= 0.004, 95%, CI 15-37). Although whether this approach is optimal for patients with refractory disease is unknown, we conclude that NST is superior to HDCT especially in patients with sensitive disease. This treatment should be considered for patients with indolent lymphomas who fail prior conventional treatment.