The Addition of Rituximab to Standard High Dose BEAM Chemotherapy for Autologous Stem Cell Transplant in Patients with Lymphoma Does Have a Significant Effect on Engraftment.

The addition of Rituximab to standard combination chemotherapy has significantly improved outcomes in both young and elderly patients with Non-hodgkins lymphoma (NHL). High dose chemotherapy with autologous stem cell transplant is currently the standard of care for patients with relapsed hodgkins lymphoma (HL) and NHL. However the effect of the addition of Rituximab to standard high dose chemotherapy regimen for autologous stem cell transplant on neutrophil and platelet engraftment is unknown. There are however, reported cases of neutropenia developing in patients treated with Rituximab. We performed a retrospect review of all patients with HL and NHL treated in our institution with RBEAM (Rituximab, Carmustine, Etoposide, Cytarabine, Melphalan) chemotherapy between July 2000 and June 2005 and compared it to patients receiving BEAM in the same time period. Rituximab was given at a dose of 375mg/m2 one day prior to beginning standard BEAM high dose chemotherapy. Peripheral blood was the main source of stem cells. The purpose of this study was to determine the effect of the addition of Rituximab on neutrophil and platelet engraftment. A total of 46 patients were treated during this time period. Twelve patients received RBEAM and 34 received BEAM. There was a statistical significant difference in age between the two groups. There was however no difference between the two groups in terms of race, sex and primary diagnosis. Median stem cell dose was not significantly different between the two groups. Characteristic of both groups are shown in Table: 1

Neutrophil engraftment was defined as the first day of ANC > 500 on 3 consecutive days. Platelet engraftment was defined as the first day of platelet count > 20,000 with no platelet transfusion in the next seven days. The median time to neutrophil engraftment was 12 day in RBEAM compared to 11 days in BEAM (p=0.09). Platelet engraftment was however significantly delayed in patients receiving RBEAM 18days versus 12 days for BEAM (p= 0.02). Looking at both cohorts together we found that patients with HL had a significant delay in platelet engraftment compared to those with NHL (p=0.04). However there was no difference in neutrophil recovery. Although, stem cell dose affected neutrophil recovery, it had no effect on platelet engraftment. There was no increased toxicity in the early post transplant period associated with the addition of Rituximab. No bleeding complications resulted form the delay in platelet engraftment in the patients who received RBEAM. In a linear regression model the only factor that significantly affected engraftment was conditioning regimen. We conclude that the addition of Rituximab to standard high dose BEAM chemotherapy for autologous stem cell transplant has no effect on neutrophil engraftment; however platelet engraftment may be delayed. The continue use of this regimen despite the small delay in platelet engraftment will depend on whether there is any benefit, in terms of response rate, progression free and overall survival.