ABSTRACT
Acute promyelocytic leukemia (APL) is a type of acute myeloid leukemia (AML) characterized by the presence of t(15;17)(q22;q21) translocation leading to fusion between PML and RARa gene. Treatment combining all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) has dramatically improved the prognosis of APL. We report a rare finding of primary clone of t(15;17) followed by a sequential clonal evolution of additional derivative chromosome 6 formation by a two hit mechanism. Our case showed a good clinical response with a four years and nine months event free survival after ATRA and ATO combination therapy in spite of existence of three chromosomal abnormalities stating that targeted therapy overcomes the adverse effects of additional genetic markers. However, close monitoring with assessment for long term prognostic behavior is required.
ABSTRACT
INTRODUCTION: To compare the efficacy and safety of imatinib and cytarabine (ara-c) combination versus imatinib monotherapy in newly diagnosed patients with chronic phase chronic myeloid leukemia (CML-CP). MATERIALS AND METHODS: This prospective, randomized study included adult patients (age >18 years) with newly diagnosed CML-CP. Patients received either a single oral dose of imatinib 400 mg/day in combination with a subcutaneous injection of ara-c 20 mg/m2/day (imatinib + ara-c) or a single oral dose of imatinib 400 mg/day. Primary endpoints were hematological and molecular responses at 3 months and cytogenetic responses at 6 and 12 months. Secondary endpoints included grade 3/4 hematological and nonhematological adverse events (AEs). RESULTS: Of 30 patients included, 14 were randomized to imatinib + ara-c and 16 to imatinib alone. Complete hematologic response (CHR) at 3 months was higher with imatinib + ara-c vs. imatinib alone (100% vs. 87.5%, P = 0.48). The median time to achieve CHR was significantly (P < 0.001) lower with imatinib + ara-c (32.07 vs. 23.43 days). Molecular response at 3 months was significantly higher (P = 0.04) with imatinib + ara-c vs. imatinib alone (100% vs. 68.75%). Complete cytogenetic response was also higher with imatinib + ara-c vs. imatinib alone (42.85% vs. 25% at 6 months and 71.4% vs. 62.5% at 12 months). Neutropenia followed by thrombocytopenia and anemia were the most common AEs. Grade 3/4 hematological and nausea events were significantly (P < 0.05) higher with imatinib + ara-c. Other nonhematological events were not significantly different between the treatments. The median follow-up duration was 20 months (range: 15–23 months). CONCLUSION: Imatinib with low-dose ara-c can be considered as a potential first-line treatment option for CML-CP.