[Results up to now of administration of STI-571 (Glivec) in recurrence after allogenic and autologous stem cell transplantation in chronic myeloid leukemia].
BACKGROUND
Gleevec (STI-571) is s selective inhibitor of the bcr/abl tyrosine kinase. Recent phase I and phase II studies in patients with bcr/abl positive CML and ALL showed a low rate of grade III/IV toxicity and good clinical efficacy. This report describes the preliminary results in patients relapsing post autologous or allogeneic peripheral blood stem cell transplantation. The focus of this analysis will include toxicity, feasibility and clinical efficacy.


RESULTS
18 of 18 patients with cytogenetic and/or hematologic relapse in chronic phase CML post autologous stem cell transplantation achieved a complete hematologic remission upon therapy with Gleevec. The cytogenetic response rate was 75% with a complete cytogenetic response rate of 50%. After allogeneic stem cell transplantation, patients in cytogenetic or hematologic relapse also experienced high hematologic and cytogenetic response rates upon therapy with Gleevec. In these patients, Gleevec was shown to induce mixed chimerism. Overall, Gleevec was well tolerated after autologous and allogeneic stem cell transplantation. Most common side effects were mild to moderate gastrointestinal discomfort and edema. No symptoms of chronic extensive or > grade I acute GvHD could be observed. Hematologic toxicity was dependent on stage of disease. Grade III/IV granulocytopenia and/or thrombopenia could be observed in 50% of patients with transformed phases of CML. Management of these patients required frequent controls of peripheral blood counts and transfusion of blood products.


CONCLUSIONS
These results show a new approach in treatment of patients with Philadelphia-chromosome-positive leukemia relapsing post autologous or allogeneic stem cell transplantation. Gleevec is able to induce mixed chimerism without induction of severe GvHD. The data suggest that early start of STI-571 therapy in MRD-positive patients is a promising approach. Recently, a multicenter phase II study to evaluate the toxicity and efficacy of Gleevec in CML patients with minimal residual disease post allogeneic transplantation was started.
Fischer
Thomas
T
III. Medizinische Klinik und Poliklinik, Hämatologie und Onkologie, Johannes-Gutenberg-Universität Mainz. t.fischer@3-med.klinik.uni-mainz.de
D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001549:Benzamides; D002648:Child; D002986:Clinical Trials as Topic; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D012074:Remission Induction; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D001549:Benzamides; D004791:Enzyme Inhibitors; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate