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High-dose irradiation before HSCT increases risk for subsequent malignancies
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Survivors of allogeneic hematopoietic cell transplantation who underwent high-dose total body irradiation incurred nearly eight times the risk for subsequent malignant neoplasms compared with the general population, according to study results published in Blood.
Results showed the association to be strongly dose- and fractionation-dependent, and total body irradiation doses for nonmyeloablative conditioning posed no increased risk above that of myeloablative chemotherapy-only based regimens.
“The big takeaway is that people need to be aware of this risk,” Scott Baker, MD, director of the Fred Hutch survivorship program at Fred Hutchinson Cancer Research Center, said in a press release. “For those patients who received high-dose radiation, they need to be especially vigilant about following all the standard cancer prevention and screening recommendations. And younger patients, especially women, should talk to their doctor about starting screening for some cancers, such as breast, at an earlier age than recommended for this general population.”
In the retrospective study, Baker and colleagues evaluated 4,905 patients (57.4% men; 91.8% white) who underwent HSCT between 1969 and 2014 and had survived at least 1 year without subsequent malignant neoplasms. Patients had undergone the transplants for hematologic malignancies (n = 4,500) or nonmalignant conditions (n = 405). Median age at time of transplantation was 34.5 years (range 0.3-78.9),
Risk factors assessed by the researchers included sex, race, age at first transplant, diagnosis for transplant, stem cell source, regimen (including dose and fractionation) and development of graft-versus-host disease as a time-dependent covariate.
Eleven percent of the HSCT recipients (n = 499) developed a total of 581 subsequent malignant neoplasms at a median 10.3 years (range, 1-39.7) after HSCT.
With a median follow-up of 12.5 years (range, 1-42.11) among 1,709 surviving patients,
observed a 22% cumulative incidence of subsequent malignant neoplasms at 30 years post-HSCT.
Compared with SEER population rates matched for age, sex and calendar year, results showed a 2.8-fold (95% CI 2.6-3.1) increase in the standardized incidence ratio of subsequent malignant neoplasms.
The highest SIRs were for subsequent malignant neoplasms in the bones (28.8), oral cavity (13.8), skin (7.3), central nervous system (6) and endocrine organs (4.9).
(EARs) for subsequent malignant neoplasms per 1,000 person-years were seen in cancers of the breast (EAR = 2.2; 95% CI, 1.4-3), oral cavity (EAR = 1.5; 95% CI, 1.2-2) and skin (EAR = 1.5; 95% CI, 1.5-2).
Survivors exposed to either unfractionated (600 cGy-1,200 cGy-1,200 cGy) or high-dose fractionated (1,440 cGy-1750 cGy) total body irradiation had the highest incidence of subsequent malignant neoplasms. Those who received low-dose total body irradiation (200 cGy-450 cGy) demonstrated risk comparable to that of chemotherapy alone, albeit still twice that of the general population.
Patients aged 20 years and younger at the time of transplant had the highest risk for subsequent malignant neoplasms compared with age-matched members of the general population, although this risk decreased with longer follow-up in relation to transplant.
Patients aged 50 and older at the time of transplant showed sustained elevated SIRs over time, although follow-up beyond 20 years for these patients could not be accessed. Those aged 20 years or younger at the time of transplantation had a 2.28-times (95% CI, 1.31-3.96; P = 0.003) higher risk for subsequent malignant neoplasms than patients aged 50 years and older.
Risk for subsequent malignant neoplasms also appeared significantly higher among recipients of cord blood (HR = 3.02, 95% CI, 1.29-7.09) and peripheral blood stem cells (HR = 1.55; 95% CI, 1.16-2.07) vs. bone marrow, including after adjustment for acute and chronic GVHD.
“The ultimate goal for the transplant world is to find effective, nonradiation conditioning regimens, especially for children,” Baker said in the press release. – by Jennifer Byrne
Disclosures: The authors report no relevant financial disclosures.
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