Long-term follow-up of high-dose mitoxantrone-based induction therapy for patients with newly-diagnosed acute myelogenous leukemia. Twelve year results from a single institution

Abstract

This report provides long-term results of the treatment of patients with newly-diagnosed AML with a single high dose of mitoxantrone combined with once daily cytarabine. One-hundred and sixty-five patients treated on four studies of high-dose mitoxantrone-based induction therapy are included. Patients with a prior antecedent hematologic disorder were eligible. The median follow-up time is 65.9 months (95% CI: 55.7-86.2 months). The overall complete remission rate was 64%, with responses in 78% of patients less than 60 years of age and 51% of patients 60 years of age or older. The median duration of response is 21.2 months and 8.0 months and overall survival is 15.4 months and 7.6 months, respectively. For a sub-set of patients who would be eligible for most US trials, the complete remission rate was 84% in younger patients and 60% in older patients. The median duration of response was 39.0 and 8.2 months and the median overall survival was 19.4 and 7.6 months, respectively. The efficacy of these regimens compared favorably to results reported with standard '3 + 7' regimens. Use of a once-daily cytarabine regimen resulted in almost no neurotoxicity and allowed for administration of consolidation in the outpatient setting.

Treatment of therapy-related myeloid neoplasms with high-dose cytarabine/mitoxantrone followed by hematopoietic stem cell transplant

“…Our findings are similar to published experience of treating patients with AML with mitoxantrone or high-dose daunorubicin, in which cardiac toxicity is seen at the 5-10% range [22,27]. Seiter et al found significant cardiac toxicity in 165 patients with AML treated with multiple rounds of mitoxantrone-based induction chemotherapy for AML [22].…”

“…Our high-dose cytarabine and mitoxantrone combination resulted in a CR rate of 66% and a PR rate of 16% (95% CI 47-81% and 5-33%, respectively), which compare favorably with the remission rates that have been achieved for patients with de novo AML who received similar therapy [21][22][23][24][25]. Among these studies, remission rates of 58-64% have been achieved, with remission rates of 70-84% occurring in patients less than 60 years old.…”

“…Although our patients received only one cycle of induction therapy, they had all received prior chemotherapy, given the nature of t-MN. A feature common to our experience and published reports is cardiac decompensation with sepsis [22,28], and therefore aggressive management of neutropenic fever is advised. Because successful transplant requires adequate cardiac function, careful attention must be given to the cardiac status of patients treated with our induction regimen.…”

“…Seiter et al found significant cardiac toxicity in 165 patients with AML treated with multiple rounds of mitoxantrone-based induction chemotherapy for AML [22]. In their study, 25% of patients experienced a decrease in ejection fraction after three cycles of chemotherapy, increasing to 33% of patients by cycle 5.…”

Elderly do benefit from induction chemotherapy: High dose mitoxantrone‐based (“5 + 1”) induction chemotherapy regimen in newly diagnosed acute myeloid leukemia

“…In a phase I study of this combination, reversible hyperbilirubinemia was the dose‐limiting toxicity observed in 25% of all patients . In 2006, Seiter et al published a 12‐year follow‐up of HDM‐based induction for newly diagnosed AML patients from their institution. A total of 165 patients received HDM with high dose Ara‐C over a period from 1991 to 2003.…”