Isophosphamide therapy for hematologic malignancies in patients refractory to prior treatment

Isophosphamide was administered to 27 patients with acute leukemia and to 15 patients with malignant lymphoma refractory to primary therapy. The starting dose of isophosphamide was 1200 mg/m2 administered as a daily continuous infusion x 5 days; the courses of treatment were repeated every 2-3 weeks. Of the 27 patients with acute leukemia, four achieved complete remission, two achieved partial remission, and two achieved hematologic improvement. However, no responses occurred in ten patients with acute myelogenous leukemia (AML). Thus, the response rate was 47% (eight responses among among 17 patients, in patients with acute lymphoblastic leukemia and acute undifferentiated leukemia. Seven of the 15 patients with malignant lymphoma responded. Most responses (five of six patients) occurred in patients with diffuse histiocytic lymphoma. Twenty-one of the 42 patients had received prior therapy with cyclophosphamide and 12 of these patients (two with leukemia and ten with lymphoma) responded, thus suggesting that as in the treatment of L1210 leukemia, isophosphamide is effective for tumors resistant to prior cyclophosphamide therapy. No significant genitourinary toxicity occurred; however, myelosuppression became the dose-limiting toxicity. Isophosphamide is active in malignant lymphomas and acute leukemias (except AML) and may have a role in combination regimens for such diseases.