抄録
There are some refractory lymphomas those 5-year overall survival rate is less than 50%, including relapsed or chemotherapy-resistant aggressive NHL, high-intermediate-, or high-risk group of aggressive NHL categorized by International Prognostic Index, mantle cell lymphoma, advanced NK/T cell lymphoma, adult T-cell leukemia/lymphoma (ATL) and advanced and refractory follicular lymphoma. We report here the results of three clinical trials for these refractory lymphomas, as follows; (1) phase I/II trial of cure-oriented high-dose chemoradiotherapy with transplantation of CD34+ peripheral blood stem cells purified by the immunomagnetic bead method for refractory hematological malignancies. (2) phase I study of cladribine (2-chlorodeoxyadenosine) in lymphoid malignancies. (3) clinical trial of chimeric anti-CD20 monoclonal antibody (IDEC-C2B8) in patients with recurrent B-cell lymphoma.
(1) Nine patients with relapsed or refractory hematological malignancies including 8 NHL patients were enrolled and treated by high-dose chemoradiotherapy with transplantation of CD34+ peripheral blood stem cells purified by the immunomagnetic bead method. In each patient, a median of 1.75×106cells/kg purified CD34+ PBSCs (purity; 92%) were infused. Median times to hematopoietic recovery were as same as those in non-purged PBSCT. Most patients experienced only transient toxicities previously observed with the preparative chemotherapy regimens used. Seven patients are alive in remission. This phase I/II trial showed PBSCT with the immunomagnetic bead method to be an active and safe therapy. (2) To clarify the toxicity profiles of cladribine, we conducted a phase I and pharmacological study of cladribine with a schedule of seven-day continuous intravenous infusion every 28 days up to a maximun of three cycles. Anti-tumor effect was observed in the patients with ATL, cutaneous T-cell lymphoma and mantle cell lymphoma. The encouraging results prompted us to plan subsequent phase II studies of cladribine against ATL, hairy cell leukemia and indolent lymphoma. (3) A phase I/II trial of a chimeric mouse human monoclonal antibody to CD20 for CD20 positive recurrent indolent B-cell lymphoma in USA showed a response rate of 50%. A phase II trial has been started for recurrent or relapsed mantle cell lymphoma and indolent B-cell lymphoma in Japan. These three clical trials showed that CD34+ PBSCT by the immunomagnetic bead method, cladribine and IDEC-C2B8 are safe and active therapy or drugs, and suggested promising method or agents for refractory lymphomas.
