Late thyroid complications in survivors of childhood acute leukemia. An L.E.A. study

Abstract

Thyroid complications are known side effects of irradiation. However, the risk of such complications in childhood acute leukemia survivors who received either central nervous system irradiation or hematopoietic stem cell transplantation is less described. We prospectively evaluated the incidence and risk factors for thyroid dysfunction and tumors in survivors of childhood acute myeloid or lymphoid leukemia. A total of 588 patients were evaluated for thyroid function, and 502 individuals were assessed for thyroid tumors (median follow-up duration: 12.6 and 12.5 years, respectively). The cumulative incidence of hypothyroidism was 17.3% (95% CI: 14.1-21.1) and 24.6% (95% CI: 20.4-29.6) at 10 and 20 years from leukemia diagnosis, respectively. Patients who received total body irradiation (with or without prior central nervous system irradiation) were at higher risk of hypothyroidism (adjusted HR: 2.87; P=0.04 and 2.79, P=0.01, respectively) as compared with transplanted patients who never received any irradiation. Patients transplanted without total body irradiation who received central nervous system irradiation were also at higher risk (adjusted HR: 3.39; P=0.02). Patients irradiated or transplanted at older than 10 years of age had a lower risk (adjusted HR: 0.61; P=0.02). Thyroid malignancy was found in 26 patients (5.2%). Among them, two patients had never received any type of irradiation: alkylating agents could also promote thyroid cancer. The cumulative incidence of thyroid malignancy was 9.6% (95% CI: 6.0-15.0) at 20 years. Women were at higher risk than men (adjusted HR: 4.74; P=0.002). In conclusion, thyroid complications are frequent among patients who undergo transplantation after total body irradiation and those who received prior central nervous system irradiation. Close monitoring is thus warranted for these patients. Clinicaltrials.gov identifier: NCT 01756599.

Trial registration: ClinicalTrials.gov NCT01756599.

Figure 1.

Cumulative incidences of hypothyroidism. (A) Cumulative incidence of hypothyroidism; impact of transplantation and irradiation type. (P<10⁻³). (B) Cumulative incidence of hypothyroidism in patients treated with hematopoietic stem cell transplantation without total body irradiation (n=135): comparison between patients who received prior central nervous system irradiation and patients who did not (P=0.005). (C) Cumulative incidence of hypothyroidism among patients treated with hematopoietic stem cell transplantation who received total body irradiation as part of their conditioning: comparison between patients who were exposed to central nervous system irradiation and those who were not (P=non significant). HSCT: hematopoietic stem cell transplantation; CNS: central nervous system. TBI: total body irradiation.

Figure 2.

Cumulative incidence of thyroid cancer. The figure shows the cumulative incidence of thyroid cancer in the whole cohort (green line), and a comparison of the incidence between females (blue line) and males (red line). P<0.001.