CD34+ cell selection minimizes graft-versus-host disease (GVHD) after haploidentical donor stem cell transplant but is associated with slow immune recovery and infections. We report a Phase I/II study of prophylactic donor lymphocyte infusion (DLI) followed by methotrexate (MTX) GVHD prophylaxis after CD34-selected haploidentical donor transplant. A prophylactic DLI was given between day +30 and +42. Rituximab was given with DLI for the last 10 patients. The goal of the study was to determine a DLI dose that would result in a CD4+ cell count > 100/µL at Day +120 in ≥ 66% of patients with ≤ 33% grade II-III, ≤ 17% grade III, and no grade IV acute GVHD by Day +180. Thirty-five patients with malignant (n = 25) or nonmalignant disease (n = 10) were treated after CD34-selected haploidentical donor peripheral blood stem cell transplant. The DLI dose of 5 × 104 /kg met the CD4/GVHD goal with 67% of patients having CD4+ cells > 100/µL and 11% grade II-IV acute GVHD. The cumulative incidence of chronic GVHD was 16%. Fatal viral and fungal infections occurred in 11%. The 2 year estimated overall survival was 69% and the relapse rate was 14% for patients in remission at transplant. There was no effect of NK alloreactivity on relapse. Nine of ten patients at the target DLI dose cohort of 5 × 104 /kg are alive with median follow-up of 18 mos (range 6-29). Delayed prophylactic DLI and MTX was associated with promising outcomes at the target DLI dose. This trial was registered at clinicaltrials.gov, # NCT01027702.
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