We previously reported a 24% 1-year relapse rate in 93 older or medically unfit patients with CD20+ B-cell malignancies after low-intensity conditioning and allogeneic hematopoietic cell transplantation. The current prospective study tested the hypothesis that disease relapse could be reduced, and overall survival improved, by peri-transplant rituximab. Sixty-three patients received rituximab (375 mg/m/day) on days -3, +10, +24 and +38 in addition to 2-3 Gy total body irradiation ± fludarabine (30 mg/m × 3 days). Median rituximab levels of >25 μg/mL were achieved through day +84 after transplant, but levels were not correlated with relapse or graft-vs.-host disease incidence. Recipients with F/F and V/F FCγRIIIa polymorphisms showed a trend toward higher relapse rates compared to recipients with V/V polymorphism (p=0.15). No difference in outcome was found with V/V donor pairing. Five-year relapse rates were similar among rituximab-treated patients and historical controls (32% vs, 28%; P=0.94). Rituximab-treated patients experienced higher 5-year overall survival and progression-free survival (47% vs. 38%; P=0.13, 41% vs. 32%; P=0.12, respectively) compared to historical controls transplanted without rituximab, although not statistically significant. Incidences of acute graft-vs.-host disease were similar (Grade II-IV, 57% vs. 56%; Grade III-IV, 13% vs. 17%); and 5-year chronic graft-vs.-host disease incidence was higher among rituximab-treated patients (62% vs. 47%). In patients with relapsed or refractory non-Hodgkin lymphoma, peri-transplant rituximab neither reduced relapse nor improved graft-vs.-host disease. The role of donor-recipient pairing by FCγRIIIa polymorphisms in outcome remains to be determined.Copyright © 2020. Published by Elsevier Inc.