Abstract • 195

A major challenge in treatment of childhood ALL is cure following relapse despite multiagent chemotherapy. Combining immunotoxin with conventional chemotherapy is an alternative strategy to enhance antileukemia effect with non-overlapping toxicities. B43-PAP immunotoxin is directed against the CD19 antigen. CD 19+ lymphoid cells show a high affinity for the B43 monoclonal antibody and when bound CD19+ lymphoid cells are capable of internalization of the B43-PAP immunotoxin resulting in inhibition of protein synthesis. A Phase I study of B43-PAP immunotoxin was performed in children with relapsed ALL who were concurrently receiving a standard 4-drug reinduction (vincristine, prednisone, L'asparaginase, daunomycin). The goals of the study were to assess toxicity of B43-PAP immunotoxin at two different dose levels and feasibility of administration with standard 4-drug reinduction. Patients with relapsed ALL (>50% CD19+) <21 years of age with normal renal, liver, cardiac and pulmonary functions were eligible. Patients received B43-PAP immunotoxin daily on days 9-13 and 21-25. Twenty-four patients were entered on study (21 received at least one dose of immunotoxin), 18 were evaluable for toxicity, 15 for response. The median age was 10 (range 4-17 years). One patient at 1 mg/m2/d experienced grade 4 myalgias. Dose-limiting toxicity was seen in 3 (out of 11 patients) at 1.5 mg/m2/d. Two patients experienced grade 3 or 4 transaminase elevations. There were ten complete remissions, two patients reached a partial remission and three had progressive disease or no response. We conclude that the combination of B43-PAP immunotoxin can be given safely in patients with ALL with a 4-drug induction. In light of the efficacy of this approach, we have implemented this in one of the treatment arms of our protocol for newly diagnosed high risk ALL.