Campath-IH Combined with Fludarabine/Cyclophophamide/Rituximab (FCR) as Conditioning for Unrelated Non-Myeloablative Hematopoietic Transplantation (NMT) for Non-Hodgkin’s Lymphoma (NHL): Low Mortality Rate and Lower Than Expected Incidence of Cytomegalovirus (CMV) Reactivation.

Graft-versus-host disease (GVHD) remains a significant cause for morbidity following unrelated hematopoietic transplantation. We investigated the addition of Campath-IH in vivo, at a total dose of 45 mg, to the FCR conditioning regimen for unrelated NMT for relapsed chemosensitive NHL. 25 consecutive patients (pts) with various lymphoid histologies {Follicular = 9, Mantle cell = 7, Large cell =9}were treated. Median age was 52 yrs (range, 31–64). Median # of prior chemoregimens received was 3, and 5 pts (20%) had failed a prior autologous transplant. Ten pts (40%) were in complete remission, and 15 (60%) had evidence of active disease at study entry. Pts received rituximab at 375 mg/m² on day −8, −1, +6 and +13. Campath-IH 15 mg/iv was given daily on days −4,−3,−2. Chemotherapy was provided on the same days as the Campath-IH and consisted of fludarabine 30 mg/m²/day x 3, and cyclophosphamide 1000 mg/m² /day x 3. Transplantation was given on day 0. Bone marrow was the source of graft in 20 pts (80%), and 5(20%) received peripheral blood. Tacrolimus (maintained at a low trough level of 5) and methotrexate were used as additional GVHD prophylaxis. Median time to recovery of an ANC>500 was 11 days (range, 9–21). Nine pts (36%) did not require any platelet transfusions. All pts engrafted donor cells (median 81%, at 30 days); 19 pts remained mixed chimera at the time of their last follow-up. Five pts required donor lymphocyte infusion (DLI) for disease progression: 3 achieved complete, one partial and one had no response. With a median follow-up time of 16 mos (range, 3–45 mos), overall survival was 90% (95%CI, 66–99), and the current progression-free survival rate was 68% at 18 mos. Acute GVHD occurred in one pt (grade 1) pre-DLI, and in 3 pts (one grade 1, one grade 2, and one grade 3) post DLI. Chronic extensive GVHD occurred in 3 pts pre-, and 2 additional pts post DLI. Two pts died: one of chronic GVHD, and one of disease progression. Seventeen of the 25 transplants had either the recipient or the donor with CMV-positive serology. CMV prevention consisted of a once daily dose of foscarnet, and twice-weekly screening using the CMV Direct Antibody Fluorescent Stain Antigenemia test. With this strategy, only 9 pts (36%) had evidence of CMV reactivation (defined as any detection of CMV cells). No pt developed or died from CMV disease. These data suggest that unrelated NMT after Campath-FCR conditioning is associated with a low incidence of GVHD and treatment-related mortality. Foscarnet prevention with bi-weekly CMV screening is associated with a lower than expected risk for CMV reactivation. The regimen is a promising approach for unrelated donor transplantation for patients with advanced lymphoma.