While nonmyeloablative peripheral blood stem cell transplantation (NST) has shown efficacy against several solid tumors, it is untested in nasopharyngeal cancer (NPC). In a phase II clinical trial, 21 patients with pretreated metastatic NPC underwent NST with sibling PBSC allografts, using CY conditioning, thymic irradiation and in vivo T-cell depletion with thymoglobulin. Stable lymphohematopoietic chimerism was achieved in most patients and prophylactic CYA was tapered at a median of day +30. Seven patients (33%) showed partial response and three (14%) achieved stable disease. Four patients were alive at 2 years and three showed prolonged disease control of 344, 525 and 550 days. With a median follow-up of 209 (4–1147) days, the median PFS was 100 days (95% confidence interval (CI), 66–128 days), and median OS was 209 days (95% CI, 128–236 days). Patients with chronic GVHD had better survival—median OS 426 days (95% CI, 194–NE days) vs 143 days (95% CI, 114–226 days) ( P=0.010). Thus, NST may induce meaningful clinical responses in patients with advanced NPC.