Mitoxantrone and etoposide with or without intermediate dose cytarabine for the treatment of primary induction failure or relapsed acute myeloid leukemia

Trifilio, Steven; Rademaker, Alfred; Newman, Diane; Coyle, Katherine; Carlson-Leuer, Katrin M.; Mehta, Jayesh; Altman, Jessica K.; Frankfurt, Olga; Tallman, Martin S.

doi:10.1016/j.leukres.2011.10.027

Cited by 27 publications

(19 citation statements)

References 11 publications

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“…Accordingly, in our cohort, most patients, and particularly those who had achieved CR, received an allo‐SCT, thus confirming the strong indication for allo‐SCT in 2nd CR 2,10 . Interestingly, transplant rate is higher than that observed in other studies, 27‐29,31,34‐37 which was likely due to the rise in transplantable age in most recent years, the relatively low age of our population and the usage of reduced intensity conditioning in older and intermediate fit patients. The high transplant rate should be also due to the low HCT‐CI score observed in our cohort.…”

Section: Discussionsupporting

confidence: 83%

“…The high transplant rate should be also due to the low HCT‐CI score observed in our cohort. In this context, the significant capacity of MEC to (re)induce CR in our patients’ population, coupled with the abovementioned increased propensity to allo‐SCT, even in the elderly population, translated into an OS slightly better than that reported in previous experiences 27‐29,31,34‐37 . Of note, approximately one out of five patients became long‐term survivor after MEC rescue.…”

Section: Discussionmentioning

confidence: 60%

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MEC (mitoxantrone, etoposide, and cytarabine) induces complete remission and is an effective bridge to transplant in acute myeloid leukemia

Marconi

Talami

Abbenante

et al. 2020

European J of Haematology

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Introduction Clinical response and chemosensitivity of relapse or refractory AML patients were evaluated after rescue and bridge‐to‐transplant MEC (mitoxantrone, etoposide, and cytarabine) regimen. Methods and Patients Fifty‐five consecutive AML patients were treated with MEC from 2009 to 2018. Chemosensitivity was evaluated by WT1 quantification. Results 27/55 patients (49.1%) had AML resistant to induction and 28/55 patients (50.9%) had AML relapse. 25/55 patients (45.5%) achieved a CR after one course of MEC, and 12 patients (21.8%) achieved WT1 negativity. In 12 patients, a second MEC was administered. Four out of 12 patients improved significantly their response with the 2nd MEC. MEC was an effective bridge to transplant, 32/55 patients (58.2%) received an allogenic stem cell transplant. Median overall survival (OS) from MEC was 455 days (95% CI 307‐602 days.); patient with WT1 negative CR had the best OS (P<.000). Conclusion WT1 is a useful marker of chemosensitivity after MEC as rescue and bridge‐to‐transplant therapy.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 60%

MEC (mitoxantrone, etoposide, and cytarabine) induces complete remission and is an effective bridge to transplant in acute myeloid leukemia

Marconi

Talami

Abbenante

et al. 2020

European J of Haematology

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“…2, 3 Using current therapy, patients with relapsed AML have a survival rate of less than 30% and frequently do not survive more than 1 year after relapse diagnosis. 4, 5 Unfortunately, other than the use of all-trans retinoic acid in acute promyelocytic leukemia and the option of hematopoietic stem cell transplantation, there have not been any new drug approvals or significant changes in AML therapy in recent years. The toxicity of conventional AML therapy is often problematic for older adult patients.…”

Section: Introductionmentioning

confidence: 99%

Aberrant Mer receptor tyrosine kinase expression contributes to leukemogenesis in acute myeloid leukemia

et al. 2013

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Acute myeloid leukemia (AML) continues to be extremely difficult to treat successfully, and the unacceptably low overall survival rates mandate that we assess new potential therapies to ameliorate poor clinical response to conventional therapy. Abnormal tyrosine kinase activation in AML has been associated with poor prognosis and provides strategic targets for novel therapy development. We found that Mer receptor tyrosine kinase was over-expressed in a majority of pediatric (29/36, 80%) and adult (10/10, 100%) primary AML patient blasts at the time of diagnosis, and 100% of patient samples at the time of relapse. Mer was also found to be expressed in 12 of 14 AML cell lines (86%). In contrast, normal bone marrow myeloid precursors expressed little to no Mer. Following AML cell line stimulation with Gas6, a Mer ligand, we observed activation of prosurvival and proliferative signaling pathways, including phosphorylation of ERK1/2, p38, MSK1, CREB, ATF1, AKT and STAT6. To assess the phenotypic role of Mer in AML, two independent short-hairpin RNA (shRNA) constructs were used to decrease Mer expression in the AML cell lines Nomo-1 and Kasumi-1. Reduction of Mer protein levels significantly increased rates of myeloblast apoptosis two to threefold in response to serum starvation. Furthermore, myeloblasts with knocked-down Mer demonstrated decreased colony formation by 67–87%, relative to control cell lines (P<0.01). NOD-SCID-gamma mice transplanted with Nomo-1 myeloblasts with reduced levels of Mer had a significant prolongation in survival compared with mice transplanted with the parental or control cell lines (median survival 17 days in parental and control cell lines, versus 32–36 days in Mer knockdown cell lines, P<0.0001). These data suggest a role for Mer in acute myeloid leukemogenesis and indicate that targeted inhibition of Mer may be an effective therapeutic strategy in pediatric and adult AML.

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“…Table 3 shows a summary of selected salvage regimens. [102][103][104][105][106][107][108][109][110][111] Mutation-specific targeted therapies Despite years of intense study in the field, to our knowledge no therapies were approved by the FDA for AML between 2001 and 2016. 112 Fortunately, there have been 2 recent approvals of targeted therapies for AML, namely FLT3 and IDH2.…”

Section: Insight From the Expertsmentioning

confidence: 99%

How I treat older patients with acute myeloid leukemia

Arellano

Carlisle

2018

Cancer

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Mitoxantrone and etoposide with or without intermediate dose cytarabine for the treatment of primary induction failure or relapsed acute myeloid leukemia

Cited by 27 publications

References 11 publications

MEC (mitoxantrone, etoposide, and cytarabine) induces complete remission and is an effective bridge to transplant in acute myeloid leukemia

MEC (mitoxantrone, etoposide, and cytarabine) induces complete remission and is an effective bridge to transplant in acute myeloid leukemia

Aberrant Mer receptor tyrosine kinase expression contributes to leukemogenesis in acute myeloid leukemia

How I treat older patients with acute myeloid leukemia

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