Autologous SCT In Patients (pts) with Chemotherapy-Resistant Diffuse Large B Cell Lymphoma (DLBCL) Followed by Maintenance with Rituximab.

Abstract 4598

There are few data on the use of maintenance Rituximab after auto-SCT for patients with B cell lymphoma of aggressive histology that are resistant to chemotherapy.

From May 2005 to March 2010, 25 consecutive pts underwent auto-SCT for DLBCL resistant to chemotherapy at our center. Median age 43 year (7 – 69 yrs); 11 patients were male. Two pts were HIV positive. Initial staging was II-B in 6 patients, II-EB in 4 patients, III-B 8 patients and IV-B in 7 patients. Initial IPI score was low-intermediate (13% of the pts), high-intermediate (58%) and high (29%). Nine of the 25 pts had bulky disease and 8 had visceral or bone marrow lymphomatous involvement.

The median time from diagnosis to auto-SCT was 21 months (13 – 48 m). Prior to auto-SCT, 44% of the patients received 2 chemotherapy regimens and 56% received more than 2. All pts had chemotherapy-sensitive disease to the their last chemotherapy regimen prior to auto-SCT, with 80% and 20% of the pts achieving complete and partial remission prior to transplant, respectively. Sixteen out of 25 pts received Rituximab prior to auto-SCT; of those, 5 received Rituximab in the first line chemotherapy and 11 received it as part of the rescue chemotherapy regimens.

The protocol was approved by our institutional review board and informed consent was obtained from each pt and or their guardians.

Conditioning regimen consisted of Cyclophosphamide 1500 mg/m2 (D-6 to D-3), Etoposide 400 mg/m2 (D-6 to D-3) and Carmustin 150 mg/m2 (D-6 to D-4). The median CD34+ cells/kg infused was 2.9 × 10⁶/Kg (1.9 - 8.5×10⁶). All pts received G-CSF 10 micrograms/Kg/day SC from day +1 until neutrophil engraftment.

Median time to neutrophil engraftment (ANC >500/mm3) was 8 days (5 – 17 d). Median time to platelet recover (>20,000/mm3) was 13 days (7 – 29 d). Transplant related mortality at day +100 was one in 25 pts (4%); this pt died due to multi-drug resistant Pseudomonas infection on day +17.

Rituximab 375mg/m2 weekly for 4 weeks was administered as maintenance for a total of 4 cycles (16 doses); the cycles started on days +120, +240, +360 and +480 after auto-SCT. Twelve pts developed mild infusion reaction (tremor and rash). The hematological toxicity was low; grade II neutropenia occurred in 9 out of 25 pts. The neutropenic only occurred after the forth dose of the cycle with a median duration of 5 days (2 - 13). All pts received Bactrim and Acyclovir prophylaxis for one year after the auto-SCT. There were no viral infectious complications.

Four of the 25 pts died (16%); one due to Pseudomonas infection; 3 due to relapsed disease which occurred at 6, 9 and 19 months after the transplant. Overall disease free survival was 75% with a median follow up of 31 months (6 - 55 mo). Of the five pts with refractory disease who had received Rituximab at some point prior to transplant, 2 pts relapsed and died due to refractory Lymphoma after the transplant, but 03 are alive in CR (9, 13, 21 months).

Our data suggests that the administration of Rituximab as maintenance after auto-SCT for pts with DLBCL is well tolerated and it may decrease the incidence of relapse. Randomized studies are warranted to confirm the benefit of Rituximab as maintenance in the post auto-SCT setting to decrease relapse rate.