A new multidrug reinduction protocol with topotecan, vinorelbine, thiotepa, dexamethasone, and gemcitabine for relapsed or refractory acute leukemia.

We report the results of a phase 2 nonrandomized single-arm trial of a combination therapy for relapsed or refractory leukemia. From January 1999 to June 2002, 28 patients with multiple relapsed or refractory acute leukemia received a combination of topotecan, vinorelbine, thiotepa, dexamethasone, and, for patients with an M3 marrow on day 7, gemcitabine. A total of 14 patients had pre-B-ALL (acute lymphoblastic leukemia), three had T-cell leukemia, nine acute myeloblastic leukemia (AML), and two biphenotypic leukemia. In all, 13 patients achieved a significant response (10 complete responses and three partial responses). Among the responders, five had pre-B-ALL, two had T-cell leukemias, five had AML, and one had biphenotypic leukemia. In total, 10 of these patients subsequently underwent hematopoietic stem cell transplantation, and four are alive without disease. One patient died, while in remission, of complications resulting from an episode of sepsis and pneumonia that occurred during topotecan, vinorelbine, thiotepa, dexamethasone, and gemcitabine (TVTG) reinduction. Other toxicities included grade 4 neutropenia in all patients and transient grade 2 hepatotoxicity in 10 patients (36%). In summary, we report that 47% of heavily pretreated pediatric patients with multiply relapsed or refractory leukemia achieved a significant response after therapy on the TVTG protocol. Further studies are warranted to evaluate the role of the TVTG combination in the treatment of leukemia.