# From a clone in the blood to a leukaemia: what is known, and what is done

Source: https://onco.cc/terms/rejuv-second-from-clone-to-disease/  
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## TL;DR

Chemotherapy and radiotherapy select for blood stem cells carrying particular mutations, and in a small minority one of those clones becomes a leukaemia. The useful question is not whether a clone is there but whether it will progress: most never do, and nothing has been shown to stop one that does.

## Summary

What is done about it today. Outside a research study, almost nothing, and that is the finding rather than an omission. There is no treatment shown to clear a clone, no trial showing that finding one and acting on it changes an outcome, and no guideline recommending that people be tested for it after cancer treatment. What a result does change, where one exists already, is the threshold for investigating an unexplained blood count and the weight given to alkylator exposure if further treatment is being chosen. The wave-one record on clonal haematopoiesis after cancer treatment, linked below, covers how treatment selects these clones in the first place and is not repeated here.

The step from clone to disease, measured. A case-control study at MD Anderson compared people treated for a cancer who later developed a therapy-related myeloid neoplasm with people treated for lymphoma who did not. Of 14 cases, clonal haemopoiesis was detected in pre-treatment peripheral blood in 10 (71 per cent); of 54 age-matched controls, in 17 (31 per cent). The five-year cumulative incidence of a therapy-related myeloid neoplasm was 30 per cent (95% CI 16 to 51) in people with clonal haemopoiesis against 7 per cent (2 to 21) in those without (p = 0.016). In an independent cohort of 143 lymphoma patients from a randomised front-line chemotherapy trial, five of 74 (7 per cent) developed a therapy-related myeloid neoplasm, of whom four (80 per cent) had clonal haemopoiesis, against 11 of 69 (16 per cent) among those who did not. These are small numbers, from one centre, in people selected for having stored pre-treatment blood.

How much risk a clone carries in general. Away from cancer treatment, the question has been answered at scale. Sequenced exomes from 438,890 UK Biobank participants were used to derive and validate a clonal haematopoiesis risk score. Across people with clonal haematopoiesis of indeterminate potential or clonal cytopenia of undetermined significance, ten-year probabilities of developing a myeloid neoplasm ranged from 0.0078 to 0.85, depending on which gene was mutated, how many mutations there were, the variant allele fraction, age, the presence of a cytopenia and the red cell indices. The score sorted people into low risk (10,018, 88.4 per cent), intermediate (1,196, 10.5 per cent) and high risk (123, 1.1 per cent), and most myeloid neoplasms in independent clinical cohorts occurred in the high-risk minority. The authors' framing is that the score "distinguishes a high risk minority from the majority of CHIP/CCUS which has minimal risk for progression to MN".

The limit that matters here. That score was derived in a general population, not in people who have had cancer treatment. The mutations that cytotoxic therapy selects for, in the DNA-damage genes TP53, PPM1D and CHEK2, are not the ones that dominate age-related clonal haematopoiesis, and a score trained on the latter is not known to transfer. Applying it to a survivor is an extrapolation, and anyone quoting a ten-year risk to a survivor from it should say so.

Why anyone would test at all. Two reasons, neither of them yet an indication. First, a clone found before treatment identifies a group in whom a different regimen might be preferred, which is testable and has not been tested. Second, when a therapy-related myeloid neoplasm does appear, the same mutation can usually be found in the pre-treatment sample, which establishes that the clone preceded the disease rather than arising from it. The clinical consequence of a positive test in a well person is, at present, closer to worry than to action, and a test that produces a result nobody knows how to act on is one to think about before ordering.

What would change this. A trial that enrols people with a high-risk clone after cancer treatment and randomises an intervention against observation. None has reported. Until one does, the honest position is that clonal haematopoiesis explains part of the second cancer risk and does not yet reduce it.

## Fields

- Kind: Term
- Last checked: 2026-10-02
- Also known as: CHIP progression; Clonal haematopoiesis and therapy-related myeloid neoplasm; Clonal haematopoiesis risk score
- Tags: rejuvenation; survivorship; second-cancers; blood; biomarker

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Clonal_hematopoiesis
- Takahashi et al., Preleukaemic clonal haemopoiesis and risk of therapy-related myeloid neoplasms: a case-control study (Lancet Oncol 2017): https://doi.org/10.1016/S1470-2045(16)30626-X
- Weeks et al., Prediction of risk for myeloid malignancy in clonal hematopoiesis (NEJM Evidence 2023): https://doi.org/10.1056/evidoa2200310
- 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

- technologies: [Clonal haematopoiesis after cancer treatment](https://onco.cc/technologies/rejuv-age-clonal-haematopoiesis-after-therapy/), [Survivorship care and late-effects surveillance](https://onco.cc/technologies/survivorship-care-plan/), [Whole-exome & whole-genome sequencing](https://onco.cc/technologies/wes-wgs/)
- terms: [Alkylating agents and therapy-related myeloid neoplasms](https://onco.cc/terms/rejuv-second-alkylating-agents-and-myeloid-neoplasms/), [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/), [Topoisomerase II inhibitors and the shorter latency](https://onco.cc/terms/rejuv-second-topoisomerase-inhibitors-short-latency/)
- 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/)
- fronts: [Recovery & Rejuvenation](https://onco.cc/fronts/rejuvenation/), [Supportive Care & Survivorship](https://onco.cc/fronts/supportive-care/)
- pathways: [Clonal haematopoiesis (CHIP)](https://onco.cc/pathways/clonal-haematopoiesis/)
- bottlenecks: [Biomarkers are not validated or standardised](https://onco.cc/bottlenecks/b-biomarker-validation/), [Overdiagnosis and false alarms](https://onco.cc/bottlenecks/b-overdiagnosis/), [Survivorship and late effects are neglected](https://onco.cc/bottlenecks/b-survivorship/)

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