Abstract

Rituximab is a chimeric murine/human IgG1 kappa anti-CD20 monoclonal antibody that has revolutionized treatment of patients with CD20+ malignancies because of its non-cross resistance with chemotherapy and favorable toxicity profile. There is limited data evaluating the feasibility of combining rituximab with conditioning chemotherapy (or chemo-radiotherapy) for patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) for advanced CD20+ expressing malignancies. Twelve patients (M= 7; F=5), with a median age of 54.5 (41–66) years, underwent allo-HCT for the following diagnoses (disease status at time of transplantation) [chronic lymphocytic leukemia (CLL)= 7 (CR2=2; PR2= 3; ≥PR3=2); mantle cell lymphoma (MCL)= 3 (CR1=1; ≥PR2= 2); follicular NHL=1 (CR3=1), diffuse large B-cell (DLBC)=1 (>PR3=1)]. Donors were as follows: matched-related donors (MRD) = 7; matched-unrelated donors (MUD) =3; mismatched unrelated donor (MMUD)= 2. Fludarabine-based conditioning regimens comprised fludarabine plus targeted doses of intravenous busulfan (FLU-BU=8), or total-body irradiation (FLU-TBI=3), or cyclophosphamide (FLU-CY=1). Anti-thymocyte globulin (ATG) was administered in two cases of MMUDs. GVHD prophylaxis consisted of tacrolimus plus mycophenolate mofetil= 8, or methotrexate = 4. Nine (75%) of 12 patients received rituximab 375 mg/m2 on day +1 (±3 days) and all (100%) patients received rituximab 375 mg/m2 on day +8 (± 3 days) without serious infusion reactions. All patients engrafted. Median time to neutrophil engraftment for the entire cohort was 15.5 (12–27) days. Median time to platelet engraftment in nine patients was 14.5 (10–17) days. Three patients never dropped their platelet counts below 20,000/uL. Median donor chimerism at day +90 (±10 days) for unsorted BM, CD3 and CD33 by PCR/STR method were 94% (70–100%), 86% (59–100%) and 100%, respectively. At a median follow up of 5 (0.6–30.3) months, the 100-day non-relapse mortality (NRM) in 11 evaluable patients was 10%. Acute GVHD, grades II, III, and IV, developed in 50%, 8.3% and 8.3%, respectively, at a median time of 27 (16–77) days. These findings demonstrate that administration of rituximab as part of conditioning chemotherapy is feasible and does not affect timely hematopoietic engraftment of allograft recipients with advanced CD20+ malignancies.

Author notes

Disclosure: No relevant conflicts of interest to declare.