Therapy-related Myeloid Neoplasms: Considerations for Patients' Clinical Evaluation

Sep 24, 2026

Therapy-related myeloid neoplasms (t-MNs) are a distinct subgroup of myeloid malignancies arising after exposure to radio/cytotoxic agents used to treat unrelated diseases. These cases show unique clinical patterns, including older age, higher comorbidity burden, and unfavorable genetic profiles, supporting the need for dedicated diagnostic workups and treatment algorithms. As modern classification highlights patient-specific features rather than history alone, optimizing fitness assessment in this setting remains largely unexplored. This review summarizes patient, treatment, and disease factors for planning therapies with an optimal risk/benefit ratio.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages7

Reading Time18 min

AccessFree to download

Introduction

Therapy-relatedness as a disease qualifier

Current Status of t-MNs Classification

WHO changes and the role of clonal hematopoiesis

ICC priorities and morphologic/genetic classification

Historical evolution of trigger drugs and latency

Mediterranean Journal of Hematology and Infectious Diseases Review Article Therapy-related Myeloid Neoplasms: Considerations for Patients’ Clinical Evaluation Raffaele Palmieri 1,2, Giovangiacinto Paterno 1, Flavia Mallegni 1, Federica Frenza 1, Ilenia De Bernardis 1, Federico Moretti 1, Elisa Meddi 1, Maria Ilaria Del Principe 1, Luca Maurillo 1, Adriano Venditti 1 and Francesco Buccisano 1. 1 Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy. 2 Clinical Research Division, Fred Hutchinson Cancer Center, Seattle (WA), USA. Competing interests: The authors declare no conflict of Interest. Abstract. Therapy-related myeloid neoplasms (t-MNs) encompass a specific sub-group of myeloid malignancies arising after exposure to radio/cytotoxic agents for the treatment of unrelated diseases. Such malignancies present unique features, including advanced age, high comorbidities burden, and unfavorable genetic profiles. All these features justify the need for a specific diagnostic workup and dedicated treatment algorithms. However, as new classification systems recognize the unique clinical characteristics exhibited by t-MN patients, how to assess fitness status in this clinical setting is largely unexplored. Optimizing fitness assessment would be crucial in the management of t-MN patients, considering that factors usually contributing to a worse or better outcome (like age, comorbidities, and treatment history) are patient-specific. In the absence of specific tools for fitness assessment in this peculiar category of AML, the aim of this review is to describe all those factors related to patient, treatment, and disease that allow planning treatments with an optimal risk/benefit ratio. Keywords: T-AML; T-MN; Clinical evaluation. Citation: Palmieri R., Paterno G., Mallegni F., Frenza F., De Bernardis I., Moretti F., Meddi E., Del Principe M.I., Maurillo L., Venditti A., Buccisano F. Therapy-related Myeloid Neoplasms: considerations for patients’ clinical evaluation. Mediterr J Hematol Infect Dis 2023, 15(1): e2023051, DOI: [http://dx.doi.org/10.4084/MJHID.2023.051](http://dx.doi.org/10.4084/MJHID.2023.051) Published: September 1, 2023 Received: July 18, 2023 Accepted: August 11, 2023 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ([https://creativecommons.org/licenses/by-nc/4.0](https://creativecommons.org/licenses/by-nc/4.0)), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Correspondence to: Adriano Venditti, MD. Tel.: +39-06-20903226. E-mail: adriano.venditti@uniroma2.it Introduction. The specificity of myeloid neoplasms that arise following exposure to cytotoxic chemotherapy, ionizing radiotherapy, and/or immunosuppressive therapy for an unrelated antecedent disease is recognized as a specific sub-group, commonly referred to as therapy-related myeloid neoplasms (t-MNs) . 1,2 Nevertheless, according to the recent version of World Health Organization (WHO) and International Consensus Classification (ICC) of myeloid neoplasms, characteristics related to patients and disease, rather than clinical history, seem to account for the differences observed between therapy-related and de novo neoplasms. As a result, both classifications now consider therapy-relatedness as a “disease qualifier” rather than a disease defining entity.3,4 The approach to this subgroup of acute myeloid leukemias (t-AML) and myelodysplastic syndromes (tMDS) presents several challenges. In the large majority of cases, t-MNs typically present with unfavorable features, such as peripheral blood cytopenias and highrisk genetic and cytogenetic profile.5 Furthermore, from a clinical point of view, the previous exposure to anticancer treatments may significantly affect fitness for antileukemic treatment. Consequently, even for young fit patients, 5-year overall survival hardly reac

FAQs

What defines therapy-related myeloid neoplasms (t-MNs)?

t-MNs are myeloid malignancies that develop after exposure to radio/cytotoxic agents given for treatment of unrelated diseases. They represent a specific subgroup with distinctive clinical and biological features.

Why is a specific clinical evaluation needed for t-MN patients?

t-MN patients often present with advanced age, substantial comorbidities, and unfavorable genetic profiles, and prior anticancer exposure can impair fitness for antileukemic therapy. These factors support dedicated diagnostic workups and tailored treatment algorithms.

What is the goal of the review regarding fitness assessment?

The review aims to clarify the need for a specific approach to fitness evaluation in t-AML patients and to identify considerations that help select treatments, including allogeneic stem cell transplantation, with an optimal risk/benefit balance.

Sep 24, 2026

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