0000000000324883
AUTHOR
Stefan Fruehauf
Imatinib combined with mitoxantrone/etoposide and cytarabine is an effective induction therapy for patients with chronic myeloid leukemia in myeloid blast crisis.
BACKGROUND Despite advances in drug therapy and allogeneic stem cell transplantation (allo-SCT), the prognosis of patients with chronic myeloid leukemia (CML) in blast crisis remains poor. Imatinib has demonstrated synergistic effects in vitro with mitoxantrone, etoposide, and cytarabine. METHODS A Phase I/II trial was performed in patients with CML myeloid blast crisis. Patients were treated with imatinib + mitoxantrone/etoposide in four cohorts: mitoxantrone 10 mg/m2/day and etoposide 100 mg/m2/day for 2 or 3 consecutive days and imatinib 600 mg/day from Day 15 (cohorts 1 and 2) or from Day 1 (cohorts 3 and 4). After hematologic reconstitution after the cytopenic phase, cytarabine was giv…
A Multicenter Phase I/II Trial of the Combination of Imatinib Mesylate with Mitoxantrone/Etoposide and Cytarabine in Patients with CML in Myeloid Blast Crisis: A Trend to a Longer Survival in Patients Receiving More Aggressive Treatment Schedules.
Abstract The combination of imatinib with mitoxantrone, etoposide or cytarabine were shown to be additive to highly synergistic on BCR-ABL-positive leukemias in vitro by several investigators, including our group. Therefore, we initiated a phase I/II trial for patients with myeloid blast crisis of chronic myelogenous leukemia. Patients were treated in four cohorts starting from mitoxantrone 10 mg/m2/d and etoposide 100 mg/m2/d for 2 or 3 consecutive days and start of imatinib 600 mg/d from day 15 (cohorts #1 and #2) or from day 1 (cohorts #3 and #4). Cytarabine was given at a dose of 10 mg/m2/d s.c. as maintenance treatment. Seventeen patients were included in the study: 8 pts in cohort 1, …
Dynamics of BCR-ABL mRNA expression in first-line therapy of chronic myelogenous leukemia patients with imatinib or interferon alpha/ara-C.
We sought to determine dynamics of BCR-ABL mRNA expression levels in 139 patients with chronic myelogenous leukemia (CML) in early chronic phase, randomized to receive imatinib (n=69) or interferon (IFN)/Ara-C (n=70). The response was sequentially monitored by cytogenetics from bone marrow metaphases (n=803) and qualitative and quantitative RT-PCR from peripheral blood samples (n=1117). Complete cytogenetic response (CCR) was achieved in 60 (imatinib, 87%) vs 10 patients (IFN/Ara-C, 14%) after a median observation time of 24 months. Within the first year after CCR, best median ratio BCR-ABL/ABL was 0.087%, (imatinib, n=48) vs 0.27% (IFN/Ara-C, n=9, P=0.025). BCR-ABL was undetectable in 25 c…
Combination Treatment with Imatinib and Mitoxantrone/Etoposide Is a Suitable Preparative Regimen before Allogeneic Transplantation in Patients with Myeloid Blast Crisis of Chronic Myeloid Leukemia.
Abstract In advanced BCR-ABL-positive leukemia, combination of chemotherapy with imatinib is expected to result in better reduction of leukemia cell load and may delay or offset clonal selection of resistant leukemia cells, thus improving the survival. We carried out a prospective phase I/II combination trial for patients (pts) with myeloid blast crisis of chronic myelogenous leukemia (CML). Pts were treated with imatinib+mitoxantrone/etoposide in four cohorts starting from mitoxantrone 10mg/m2/d and etoposide 100 mg/m2/d for 2 or 3 consecutive days and start of imatinib 600mg/d from day 15 (coh. 1 and 2) or from day 1 (coh. 3 and 4, respectively). After hematologic reconstitution following…