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People who have had a donor transplant develop new, unrelated cancers about twice as often as people of the same age, and by fifteen years about three times as often. Radiation in the conditioning matters most for those irradiated young, and chronic GvHD raises squamous cancers of skin and mouth. Both point at lifelong screening.
The largest study of this question followed 28,874 allogeneic transplant recipients and identified 189 solid cancers. Overall, patients developed new solid cancers at twice the rate expected from general population rates, with an observed-to-expected ratio of 2.1 (95 per cent CI 1.8 to 2.5), and the risk increased over time (P for trend less than 0.001), reaching threefold among patients followed for fifteen years or more. The study's new finding concerned age at irradiation: among patients irradiated at ages under 30, the relative risk of non-squamous cancer was nine times that of non-irradiated patients, while for older patients it was 1.1, a highly significant interaction (P less than 0.01). Chronic graft-versus-host disease and male sex were the main determinants of squamous cell carcinoma risk. The authors concluded that the data support strategies to promote lifelong surveillance.
Radiation is not the whole explanation. A second study examined 4,318 recipients of a first allogeneic transplant conditioned with high-dose busulfan and cyclophosphamide, with no total body irradiation, for acute myeloid leukaemia in first remission or chronic myeloid leukaemia in first chronic phase, representing 22,041 person-years. Sixty-six solid cancers were reported at a median of six years. Cumulative incidence at five and ten years was 0.6 and 1.2 per cent for the AML group and 0.9 and 2.4 per cent for the CML group. Compared with general population rates, recipients had a 1.4-fold higher than expected rate of invasive solid cancers (95 per cent CI 1.08 to 1.79, P = 0.01), with significantly elevated risks for tumours of the oral cavity, oesophagus, lung, soft tissue and brain. Chronic graft-versus-host disease was an independent risk factor for all solid cancers and especially for cancers of the oral cavity. The authors' conclusion was that incidence continues to increase with time and lifelong cancer surveillance is warranted.
So: the excess exists with and without radiation, radiation multiplies it most in those exposed young, and chronic GvHD is a consistent independent risk factor across both studies, concentrated in the squamous epithelium it damages, skin and mouth.
What follows practically. Skin examination and mouth examination belong in routine follow-up, and in someone with chronic GvHD the mouth examination is being done for two reasons at once. Sun protection matters for a person on long-term immunosuppression in a way it does not for the general population. Smoking cessation does more here than almost anywhere else in survivorship, given the oral cavity, oesophageal and lung excesses. Population screening programmes should be entered and not skipped, and in some circumstances started earlier, which is a decision for the transplant follow-up team against the published recommendations. And new oral lesions, persistent hoarseness or a skin lesion that is changing should be examined rather than watched.
Therapy-related myeloid neoplasms and post-transplant lymphoproliferative disorder are a different problem with different timing and are not covered here: the second cancers field in adults belongs to another facet of this round, and this record is the transplant-specific part of it.
Three mechanisms overlap. Ionising radiation induces DNA damage in tissues outside the marrow, with a latency of a decade or more and a steeper dose-response in tissues that are still growing, which is why age at exposure dominates. Chronic alloimmune inflammation at epithelial surfaces, the same surfaces chronic GvHD injures, promotes squamous carcinogenesis. And prolonged immunosuppression reduces immune surveillance, particularly of virus-associated and cutaneous tumours.
Query for this technology: (TITLE:"Second cancers after allogeneic transplant" OR ABSTRACT:"Second cancers after allogeneic transplant" OR TITLE:"solid cancers after HCT" OR ABSTRACT:"solid cancers after HCT" OR TITLE:"second primary malignancy after transplant" OR ABSTRACT:"second primary malignancy after transplant" OR TITLE:"post-transplant malignancy" OR ABSTRACT:"post-transplant malignancy") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Second cancers after allogeneic transplant, not a curated reading list.
Shares Total body and total marrow irradiation, Chronic GvHD organ by organ: skin, mouth, eyes, gut, liver, joints and genital tract, Who is supposed to be watching: EBMT, CIBMTR, FACT-JACIE, and what a survivor is actually offered, Late effects after a stem cell transplant and the tags rejuvenation, survivorship, transplant, late-effects.
Shares Who is supposed to be watching: EBMT, CIBMTR, FACT-JACIE, and what a survivor is actually offered, Late effects after a stem cell transplant, After a transplant or cell therapy: what to ask for, Allogeneic stem cell transplantation and the tags rejuvenation, survivorship, transplant, late-effects.
Shares Total body and total marrow irradiation, Chronic GvHD organ by organ: skin, mouth, eyes, gut, liver, joints and genital tract, Who is supposed to be watching: EBMT, CIBMTR, FACT-JACIE, and what a survivor is actually offered, Chronic graft-versus-host disease and the tags rejuvenation, survivorship, transplant.
Shares Total body and total marrow irradiation, Late effects after a stem cell transplant, Conditioning regimen (myeloablative, reduced-intensity), After a transplant or cell therapy: what to ask for and the tags rejuvenation, survivorship, transplant, late-effects.
Shares Total body and total marrow irradiation, Late effects after a stem cell transplant, Conditioning regimen (myeloablative, reduced-intensity), After a transplant or cell therapy: what to ask for and the tags rejuvenation, survivorship, transplant, late-effects.
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Shares Chronic GvHD organ by organ: skin, mouth, eyes, gut, liver, joints and genital tract, Chronic graft-versus-host disease, After a transplant or cell therapy: what to ask for, Survivorship care and late-effects surveillance and the tags rejuvenation, survivorship, transplant.
Shares Late effects after a stem cell transplant, Chronic graft-versus-host disease, After a transplant or cell therapy: what to ask for, Allogeneic stem cell transplantation and the tags rejuvenation, survivorship, transplant.