# Topoisomerase II inhibitors and the shorter latency

Source: https://onco.cc/terms/rejuv-second-topoisomerase-inhibitors-short-latency/  
OnCo record `rejuv-second-topoisomerase-inhibitors-short-latency` (Term). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Etoposide and the anthracyclines can cause a leukaemia too, but a different one: it arrives after about two years rather than six, it starts as acute leukaemia without a myelodysplastic phase, and it carries a balanced break in a chromosome rather than a missing piece. So the first two or three years after this chemotherapy are when a blood count matters most.

## Summary

What is done about it. Again nothing preventive, so the answer is at the time of treatment and in the follow-up interval. Because the latency is short, a full blood count during the first years after an etoposide-containing or anthracycline-containing regimen is where an unexplained cytopenia is likely to show, and that is also the window in which a reader is most likely to still be under oncology follow-up rather than discharged.

Two diseases, not one. Drugs that poison DNA topoisomerase II, chiefly the epipodophyllotoxins etoposide and teniposide and the anthracyclines, produce a myeloid neoplasm with balanced translocations involving chromosome bands 11q23, where the KMT2A gene sits, and 21q22. Alkylating agents and radiotherapy produce the chromosome 5 and 7 losses described in the record beside this one. These were recognised as alternative genetic pathways long before the gene mutations behind them were found, and the cytogenetic pattern still depends on which class of drug was given.

The latency, measured. In the University of Chicago series of 306 patients with therapy-related myelodysplasia or myeloid leukaemia, patients whose disease carried a balanced rearrangement had a significantly shorter latency: a median of 28 months against 67 months for everyone else (P < .0001). They were also far more likely to present with acute leukaemia outright rather than with myelodysplasia first: 28 per cent of those presenting with acute leukaemia had a balanced rearrangement against 4 per cent of those presenting with myelodysplasia (P < .0001). That is the whole clinical difference in two numbers: sooner, and without a warning phase.

Where this matters most. Etoposide is used in testicular cancer, small cell lung cancer, lymphoma and several paediatric regimens, and the anthracyclines in breast cancer, lymphoma and leukaemia. In the SEER analysis of adults treated for a first solid cancer from 2000 onwards, therapy-related myeloid neoplasms were raised after chemotherapy for 22 of 23 solid cancer types, so this is not confined to the diseases where it was first described.

What is not known. There is no threshold dose of etoposide below which the risk is zero, and no test before treatment that identifies who will develop it. The populations in which cumulative-dose relationships have been measured most carefully are paediatric, and those cohorts belong to another facet of this round. For an adult asking whether their own etoposide dose was high enough to matter, the honest answer is that the number needed to answer that has not been published for most adult regimens.

## Fields

- Kind: Term
- Last checked: 2026-10-02
- Also known as: Etoposide-related leukaemia; 11q23 therapy-related leukaemia; KMT2A-rearranged secondary AML
- Tags: rejuvenation; survivorship; second-cancers; blood; chemotherapy

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Topoisomerase_inhibitor
- Smith et al., Clinical-cytogenetic associations in 306 patients with therapy-related myelodysplasia and myeloid leukemia: the University of Chicago series (Blood 2003): https://doi.org/10.1182/blood-2002-11-3343
- Pedersen-Bjergaard et al., Genetics of therapy-related myelodysplasia and acute myeloid leukemia (Leukemia 2008): https://doi.org/10.1038/sj.leu.2405078
- Leone et al., Therapy-related leukemia and myelodysplasia: susceptibility and incidence (Haematologica 2007): https://doi.org/10.3324/haematol.11034
- Morton et al., Association of chemotherapy for solid tumors with development of therapy-related myelodysplastic syndrome or acute myeloid leukemia in the modern era (JAMA Oncol 2019): https://doi.org/10.1001/jamaoncol.2018.5625

## Connected records

- terms: [Alkylating agents and therapy-related myeloid neoplasms](https://onco.cc/terms/rejuv-second-alkylating-agents-and-myeloid-neoplasms/), [From a clone in the blood to a leukaemia: what is known, and what is done](https://onco.cc/terms/rejuv-second-from-clone-to-disease/), [Late effects and survivorship toxicity](https://onco.cc/terms/late-effects/), [Second cancers after treatment: what the risk is, and what is done about it](https://onco.cc/terms/rejuv-second-cancers-overview/), [Secondary malignancy (therapy-related cancer)](https://onco.cc/terms/secondary-malignancy/)
- cancers: [Acute myeloid leukaemia](https://onco.cc/cancers/aml/), [Myelodysplastic syndromes / neoplasms (MDS)](https://onco.cc/cancers/mds/), [Non-Hodgkin lymphoma (all types)](https://onco.cc/cancers/non-hodgkin-lymphoma/), [Secondary and therapy-related acute myeloid leukaemia](https://onco.cc/cancers/aml-secondary/), [Small-cell lung cancer](https://onco.cc/cancers/sclc/), [Testicular germ cell tumours](https://onco.cc/cancers/testicular/)
- fronts: [Recovery & Rejuvenation](https://onco.cc/fronts/rejuvenation/), [Supportive Care & Survivorship](https://onco.cc/fronts/supportive-care/)
- technologies: [Cytotoxic chemotherapy](https://onco.cc/technologies/cytotoxic-chemotherapy/), [Survivorship care and late-effects surveillance](https://onco.cc/technologies/survivorship-care-plan/)
- drugs: [Doxorubicin](https://onco.cc/drugs/doxorubicin/), [Etoposide](https://onco.cc/drugs/etoposide/)
- bottlenecks: [Survivorship and late effects are neglected](https://onco.cc/bottlenecks/b-survivorship/), [Toxicity and quality of life are undervalued](https://onco.cc/bottlenecks/b-toxicity-qol/)

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