Dexamethasone (D), High Dose Ara-C (HA) and Carboplatin (DHAC) with or without Rituximab (R) Is an Effective Salvage Regimen for Patients with Relapsed/Refractory B-Cell Lymphoma in Preparation for Autologous Stem Cell Transplantation.

Introduction: Relapsed/refractory B-cell lymphomas are a constant treatment challenge. High- dose chemotherapy and stem cell transplant (HDC-SCT) continues to be the backbone of treatment for such patients. Adequate cytoreduction with salvage chemotherapy is necessary prior to HDC-SCT and its achievement has been demonstrated to correlate with post-transplant outcomes. Various non-cross resistant salvage regimens have been developed to treat patients with relapsed/refractory B-cell lymphoma. In this report we present our institution’s experience with DHAC±R in patients requiring salvage therapy prior to HDC-SCT.

Methods: The DHAC regimen consists of Dexamethasone at 15mg/m²/dose po every 6 hours × 10 doses, High-dose Ara-C at 3gr/m² (1.5gr/m² if >50 yrs old) iv over 3 hrs every 12 hrs for 4 doses and Carboplatin at 200mg/m² iv every 24 hrs for 2 doses. When utilized, patients received rituximab at the standard dose of 375mg/m², 48 hrs prior to each cycle of DHAC. Growth factor support and anti-microbial prophylaxis was implemented 24 hours after completion of chemotherapy. The regimen was repeated every 21 days for 2-3 cycles prior to HDC-SCT.

We treated 37 patients with relapsed/refractory lymphomas, the median age of the entire cohort was 47 years (range 18 – 78); 25 were male and 19 females. While most of the patients treated had diffuse large B-cell lymphoma (DLBCL), various histological subtypes were included (DLBCL (n=16); follicular lymphoma (n=10); marginal zone lymphoma with blastoid features (n=1); small lymphocytic lymphoma (n=1) and Hodgkin’s lymphoma (n=8). The majority of the patients presented with advance stage at the time of DHAC therapy-Stage III (n=43%), Stage IV (n=39%). Seventeen patients were treated with R+DHAC, and 20 were treated with DHAC, either as second line or third line therapy. 19 out of the 37 patients proceeded to Stem cell transplant (SCT).

Results: The overall response rate (ORR, CR+PR) for all patients was 61%(CR (n=16); and PR (n=7). The remaining 14 patients had either stable disease (n=10) or progressed (n=4). Complete responders (43%) had a longer mean survival of 107 (range 78 – 136) months compared to 66 months (range 49 – 83) for partial responders (19 percent) and non-responders who had a mean survival of 30.8 months (range 9–54), [P = 0.008]. Patients who proceeded to SCT had an overall response rate of 79% [CR (n=11) and PR (n=4)] compared to only 44% in those who did not [CR (n=5) and PR (n=3)]. The median survival in patients transplanted was longer than non-transplanted patients (92 vs 68 months). Response rates and median survival was similar between patients receiving R-DHAC or DHAC. As expected grade 3&4 hematologic toxicities were seen and effectively managed with appropriate supportive care.

Conclusions: DHAC with or without rituximab appears to be an effective salvage treatment for patients with relapsed or refractory advanced-stage B-lymphoma undergoing HDC-SCT. An overall response of 61% which increases to 79% when followed by autologous SCT were demonstrated. Median survival was longer in patients experiencing CRs compared to partial or non-responders suggesting that the quality and quantity of the cytoreduction after salvage chemotherapy is an important predictor factor of post-SCT survival. Data looking at prognostic factors predicting response to DHAC±R treatment are being analyzed and will be reported at the ASH annual meeting.