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Transplant conditioning can leave the thyroid underactive, the ovaries or testes not working, and the handling of sugar and fat altered in a way that raises heart risk years later. Much of this is treatable with ordinary medicine, and the familiar things about weight, exercise and smoking matter more here than usual, not less.
Thyroid and the other glands. Hypothyroidism, gonadal failure and growth hormone deficiency in children are standard items on the list of late effects after transplant, and the screening recommendations include thyroid function testing and gonadal assessment in long-term survivors. Thyroid failure after total body irradiation is usually primary and compensated at first, which is why a thyroid-stimulating hormone measurement finds it before symptoms do. Gonadal failure is covered on its own record below.
Metabolic consequences, and where they come from. A study enrolled 151 recipients of transplant in childhood or young adulthood, mean age 26.4 years at enrolment and 2.6 to 31.5 years from transplant, and 92 sibling controls, and measured insulin sensitivity by hyperinsulinaemic euglycaemic clamp and body composition by dual X-ray absorptiometry. Transplant recipients had lower insulin sensitivity and more adverse cardiovascular risk factors than their siblings. They had significantly higher percentage fat mass and visceral adipose tissue and significantly lower lean body mass despite a similar body mass index, a pattern the authors call sarcopenic obesity. Total body irradiation in the conditioning was one of the strongest factors associated with lower insulin sensitivity, dyslipidaemia and abnormal body composition. The finding that body mass index was the same in both groups while body composition was not is the most useful thing in that study for a reader: the scale will not show this, so it has to be looked for in the blood.
Cardiovascular disease. A cohort of 1,379 transplant recipients, 57 per cent allogeneic and 43 per cent autologous, who survived two years or more and were followed through 2008 with a median follow-up of 7.0 years, gives the incidence figures: 10-year cumulative incidence of ischaemic heart disease 3.8 per cent, cardiomyopathy 6.0 per cent, stroke 3.5 per cent and all-cause cardiovascular death 3.7 per cent. In multivariable analysis, higher pre-transplant anthracycline exposure was associated with cardiomyopathy, and active chronic graft-versus-host disease was associated with cardiovascular death (hazard ratio 4.0, 95 per cent CI 1.1 to 14.7); risk was otherwise similar between autologous and allogeneic recipients. Independent of chemotherapy and radiotherapy exposure, pre-transplant smoking, hypertension, dyslipidaemia, diabetes and obesity each conferred additional risk of all outcomes except stroke, with a hazard ratio of 1.5 or more per additional risk factor (P less than 0.03). Hypertension and dyslipidaemia present at one year and persisting two or more years after transplant were independently associated with multiple outcomes.
That last sentence is the actionable one, and it is why this record is not simply a list. The conventional risk factors keep their full predictive power in transplant survivors and add to the treatment-related risk rather than being swamped by it, which means blood pressure, lipids, glucose and smoking are worth treating here at least as hard as in anyone else. A risk prediction model built in 1,828 transplant survivors free of cardiovascular disease at one year, using age, anthracycline dose, chest radiation, hypertension, diabetes and smoking, reached an area under the curve of 0.74 and a concordance statistic of 0.72, validated in a separate 580-patient case cohort with areas under the curve of 0.66 to 0.75, and stratified patients into groups with 10-year cumulative cardiovascular disease incidence of 3.7, 9.9 and 26.2 per cent. The high-risk group carried a 7.8-fold risk (95 per cent CI 5.0 to 12.2) relative to the low-risk group. A model that separates a 3.7 per cent risk from a 26.2 per cent risk is a reasonable basis for deciding how closely to watch someone.
The NIH late effects initiative's cardiovascular working group published the field's own account of what it does not know, calling for studies aimed at understanding and preventing arterial disease and cardiac dysfunction and at decreasing hypertension, hyperglycaemia, dyslipidaemia and sarcopenic obesity after transplant. No randomised trial has shown that any post-transplant cardiovascular prevention programme changes events in this population; the case for treating the risk factors rests on their predictive power here and on trial evidence from the general population.
Total body irradiation and alkylating agents damage endocrine tissue directly and alter body composition towards visceral fat and away from lean mass, which impairs insulin sensitivity independent of weight. Anthracyclines injure cardiac myocytes before transplant; endothelial injury from conditioning, calcineurin inhibitors and chronic alloimmune inflammation adds arterial disease on top. Because conventional risk factors act on the same vasculature, their effects add rather than overlap.
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Shares Late effects after a stem cell transplant, After a transplant or cell therapy: what to ask for, Allogeneic stem cell transplantation, Survivorship care and late-effects surveillance and the tags rejuvenation, survivorship, transplant, late-effects.
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Shares Total body and total marrow irradiation, Bone, eyes, kidneys and lungs after transplant, After a transplant or cell therapy: what to ask for, Allogeneic stem cell transplantation and the tags rejuvenation, survivorship, transplant.
Shares Bone, eyes, kidneys and lungs after transplant, Late effects after a stem cell transplant, After a transplant or cell therapy: what to ask for, Autologous stem cell transplant (high-dose therapy) and the tags rejuvenation, survivorship, transplant.
Shares Bone, eyes, kidneys and lungs after transplant, After a transplant or cell therapy: what to ask for, Allogeneic stem cell transplantation, Survivorship care and late-effects surveillance and the tags rejuvenation, survivorship, transplant.
Shares Heart function after anthracyclines, trastuzumab and chest radiotherapy, Survivorship care and late-effects surveillance, Late effects and survivorship toxicity, Survivorship and late effects are neglected and the tags rejuvenation, survivorship, late-effects.