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The efficacy of murine monoclonal IgG1 antibody 2A3 specific for the 55 kD chain of the human IL-2 receptor (CD25) was evaluated for prophylaxis of acute GVHD in patients with advanced leukemia transplanted with unmodified bone marrow from related HLA-haploidentical donors incompatible for two or three HLA loci of the nonshared haplotype. As GVHD prophylaxis, 36 patients (control) received standard cyclosporine and methotrexate (C + M) whereas 11 patients (study) received C + M plus antibody 2A3, 1.0 mg/kg on day -1, and 0.5 mg/kg daily from day 0 through day +19. Antibody administration was not associated with appreciable toxicity and did not adversely affect engraftment. During treatment, circulating CD25+ cells appeared saturated by the infused antibody. Patients receiving antibody 2A3 tolerated more cyclosporine than controls (p less than 0.001) with lower increase of serum creatinine (p less than 0.05) during the first month. Seven of 10 (70%) evaluable study patients developed acute GVHD of grade II-IV with onset at a median of 20 days compared to 27 of 31 (87%) control patients with onset at a median of 13 days (p = 0.11). Trough serum levels of antibody 2A3 ranged from 7.2 to 68.8 mg/l, and lower values correlated with occurrence of acute GVHD. A human anti-mouse immunoglobulin antibody response was detected in four patients but was not associated with lower levels of antibody 2A3 in the serum. Two study patients and two controls have survived more than 1 year (p = 0.92). These findings suggest that administration of antibody 2A3 suppressed and delayed activation of alloantigen-specific T cells but did not result in their elimination.

Thirty patients undergoing allogeneic bone marrow transplantation (BMT) for hematologic malignancies received ciclosporin A (CS-A) as prophylaxis of graft-versus-host disease (GVHD). CS-A trough levels were determined in whole blood by radioimmunoassay (RIA); results were not used to adjust the CS-A dosage. Neither the dose of CS-A administered nor the CS-A concentration and fluctuation of blood levels during the first 15 days after BMT correlated with acute GVHD. Conversely in the 13 patients with acute GVHD, CS-A concentrations in the 10 days prior to the onset of the disease were increasingly lower with increasing severity of GVHD. Moreover, patients without GVHD had higher CS-A concentrations in a matched period of time. Upon withdrawal of CS-A treatment, 7 patients developed GVHD. There was no possibility to predict who would do so, but the analysis of CS-A disappearance profiles indicates that effective CS-A concentrations might be lower during long-term treatment than the concentrations required early after transplant. Despite these relationships, CS-A concentration is of little predictive value in the individual patient because of the considerable overlap among patients.