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1.
Clin Lymphoma Myeloma Leuk ; 21(2): 113-118, 2021 02.
Article in English | MEDLINE | ID: mdl-33422470

ABSTRACT

INTRODUCTION: Adults with acute myeloid leukemia (AML) have a high rate of remission; however, more than 50% relapse. C-kit is expressed in approximately 60% of patients with de novo AML and represents a potential therapeutic target. MATERIALS AND METHODS: Patients with newly diagnosed AML received 12 months of imatinib mesylate as maintenance therapy after the completion of post-remission therapy. The primary objective was to determine whether this approach improved progression-free survival (defined as no relapse and no death) compared with historical controls. RESULTS: The median progression-free survival of patients < 60 years of age was 52.1 months (historical control, 13 months) and for patients ≥ 60 years of age was 10.7 months (historical control, 8 months). The median level of AF1q expression was high (9.59), and 84% of patients had moderate or high levels of drug-resistance factors. CONCLUSIONS: Imatinib maintenance therapy may improve the outcome of newly diagnosed patients with AML who are < 60 years of age.


Subject(s)
Imatinib Mesylate/administration & dosage , Leukemia, Myeloid, Acute/drug therapy , Neoplasm Recurrence, Local/drug therapy , Protein Kinase Inhibitors/administration & dosage , Proto-Oncogene Proteins c-kit/antagonists & inhibitors , Adult , Aged , Aged, 80 and over , Female , Humans , Imatinib Mesylate/adverse effects , Leukemia, Myeloid, Acute/mortality , Leukemia, Myeloid, Acute/pathology , Maintenance Chemotherapy/methods , Male , Middle Aged , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/pathology , Progression-Free Survival , Protein Kinase Inhibitors/adverse effects , Proto-Oncogene Proteins c-kit/metabolism , Young Adult
2.
Leuk Res ; 34(12): 1622-6, 2010 Dec.
Article in English | MEDLINE | ID: mdl-20427086

ABSTRACT

The c-kit receptor is expressed in 95% of relapsed acute myeloid leukemias (AMLs) and mediates leukemic proliferation. We conducted a Phase 1 study of the c-kit inhibitor, imatinib mesylate (IM), in combination with cytarabine and daunorubicin (7+3) in c-kit+ relapsed AML. IM was dose escalated using a 3 by 3 design. Phosphorylated STAT5 was absent to minimally present in residual blasts on day 14 bone marrows. The maximum tolerated dose of IM was 300 mg. The dose-limiting toxicity was Grade 3-4 hepatic toxicity. The CR/CRp rate was 57%. Cytotoxic therapy that includes IM for relapsed AML is well-tolerated and effective.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Leukemia, Myeloid, Acute/prevention & control , Proto-Oncogene Proteins c-kit , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Benzamides , Cytarabine/administration & dosage , Cytarabine/adverse effects , Daunorubicin/administration & dosage , Daunorubicin/adverse effects , Female , Humans , Imatinib Mesylate , Leukemia, Myeloid, Acute/metabolism , Male , Maximum Tolerated Dose , Middle Aged , Phosphorylation/drug effects , Piperazines/administration & dosage , Piperazines/adverse effects , Pyrimidines/administration & dosage , Pyrimidines/adverse effects , Recurrence , STAT5 Transcription Factor/metabolism
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