Better treatment outcomes in patients with actively treated therapy-related myeloid neoplasms harboring a normal karyotype.

Sang-A Kim,Sung-Soo Yoon,Junshik Hong,Dong Soon Lee,Dong-Yeop Shin,Inho Kim,Woo Chan Park,Youngil Koh,Marina Konopleva

doi:10.1371/journal.pone.0209800

Sang-A Kim, Sung-Soo Yoon + Show 7 more

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https://doi.org/10.1371/journal.pone.0209800

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Journal: PloS one	Publication Date: Dec 31, 2018
Citations: 3	License type: CC BY 4.0

Affiliation: Seoul National University Hospital

Abstract

We analyzed treatment outcomes and prognostic factors in adult patients with therapy-related myeloid neoplasms (t-MNs) to select patients who would be benefited by active anticancer treatment. After excluding 18 patients who received palliative care only and 13 patients with acute promyelocytic leukemia, 72 t-MN patients (45 with acute myeloid leukemia and 27 with myelodysplastic syndrome) were retrospectively evaluated. Among them, 10 (13.9%), 32 (44.4%), and 30 patients (41.7%) had favorable, intermediate- and adverse-risk cytogenetics, respectively. Among patients with intermediate-risk cytogenetics, patients with a normal karyotype (NK; N = 20) showed superior allogeneic stem cell transplantation-censored overall survival (AC-OS) and OS compared to those with non-NK-intermediate-risk cytogenetics (P < 0.001). In the multivariate analysis, male sex, age ≥ 70 years, and unfavorable cytogenetics (non-NK-intermediate plus adverse risk cytogenetics) were associated with inferior AC-OS. Those results suggest that a more-refined subdivision of risk stratification would be necessary in patients with intermediate-risk cytogenetics.

Highlights

Therapy-related myeloid neoplasms (t-MNs) are myeloid malignancies diagnosed after previous exposure to cytotoxic agents employed for therapeutic purposes, mostly cytotoxic chemotherapy (CT) or ionizing radiation therapy (RT) for cancer treatment [1]. t-MNs include therapy-related myelodysplastic syndrome (t-MDS) and therapy-related acute myeloid leukemia (t-AML). t-MNs are one of the lethal long-term complications after anticancer CT/RT
Our study showed that the cytogenetic risk category contributes to prognosis prediction, as previously reported [4, 12], and a more refined classification would be possible within intermediate-risk-group patients who underwent active treatment
As for topoisomerase II inhibitor class t-MNs, DNA breaks caused by the drugs are known to frequently result in the direct induction of fusion oncogenes involving RARα at 17q21, RUNX1 at 21q22, and MLL at 11q23 [7, 15], with a relatively shorter latency of 2~3 years [1]

Summary

Introduction

Therapy-related myeloid neoplasms (t-MNs) are myeloid malignancies diagnosed after previous exposure to cytotoxic agents employed for therapeutic purposes, mostly cytotoxic chemotherapy (CT) or ionizing radiation therapy (RT) for cancer treatment [1]. t-MNs include therapy-related myelodysplastic syndrome (t-MDS) and therapy-related acute myeloid leukemia (t-AML). t-MNs are one of the lethal long-term complications after anticancer CT/RT. Therapy-related myeloid neoplasms (t-MNs) are myeloid malignancies diagnosed after previous exposure to cytotoxic agents employed for therapeutic purposes, mostly cytotoxic chemotherapy (CT) or ionizing radiation therapy (RT) for cancer treatment [1]. T-MNs include therapy-related myelodysplastic syndrome (t-MDS) and therapy-related acute myeloid leukemia (t-AML). T-MNs are one of the lethal long-term complications after anticancer CT/RT. Because almost every t-MDS eventually evolves to t-AML and similar therapeutic interventions are considered, these diseases are taken together as one distinct category in the 2016 World Health Organization (WHO) classification [2], and investigators often analyze them together [3, 4].

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