Thyroid dysfunction after bone marrow transplantation for primary immunodeficiency without the use of total body irradiation in conditioning

Abstract

Summary:Thyroid dysfunction, a common long-term complication following bone marrow transplantation (BMT), is frequently associated with total body irradiation (TBI) given in the pre-BMT conditioning protocol. We report our preliminary observation of the prevalence of thyroid dysfunction in children transplanted for primary immunodeficiency (PID) who were given cytoreductive conditioning with busulphan and cyclophosphamide, but without TBI. We evaluated thyroid-stimulating hormone (TSH) and free thyroxine (fT4) in 83 survivors transplanted between 1987 and 2002. We found nine children (10.8%) with clinical and/or biochemical thyroid dysfunction at 4 months to 4.5 years post-BMT of which three had positive antithyroid microsomal antibodies. Two patients were classified as primary and seven as compensated hypothyroidism (hyperthyrotropinaemia). Four patients with clinical features of hypothyroidism received replacement thyroxine, while five of the seven patients with compensated hypothyroidism remain off thyroxine because we suspect this may be a transient phenomenon. Abnormalities of thyroid function including severe primary hypothyroidism may occur post-BMT in children receiving chemotherapy conditioning without TBI. Thyroid function should be assessed regularly in this group of patients.

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

“…13 The use of alkylating agents may, therefore, also promote the development of thyroid cancer, as suggested by previous studies. 18,39 We, therefore, suggest that all transplanted patients be carefully monitored for thyroid malignancy, irrespectively of the conditioning regimen applied. We did not evaluate whether thyroid ultrasound scan was the best way to screen for thyroid malignancies.…”

“…In other studies concerning transplanted patients, based on smaller cohorts with various durations of follow-up, the prevalence of hypothyroidism ranged from 10.8% to 40%. 18,[28][29][30] This varying prevalence may be due to the heterogeneity of the cohorts, in terms of both follow-up time and pathology (e.g., leukemia, lymphoma, and non-malignant).…”

“…Moreover, little is known regarding the risk of thyroid complications following busulfan-containing conditioning regimens and hematopoietic stem cell transplantation. 17,18 Lastly, few studies have assessed both thyroid dysfunction and thyroid malignancies simultaneously.…”

Mini Review: Screening and Management of Late Effects in Patients with Severe Combined Immunodeficiency after Allogeneic Hematopoietic Cell Transplantation

“…Myeloablative conditioning is expected to result in greater long-lasting toxicity compared to reducedintensity conditioning, and busulfan in particular has been implicated in a number of late adverse effects, including dental anomalies, thyroid dysfunction, growth failure, and delayed puberty [28][29][30][31] . Conversely, many of these longterm complications are rare in SCID patients who do not receive preparative conditioning or post-transplant GVHD prophylaxis 32 .…”

Stem Cell Transplantation for Primary Immunodeficiency

“…Once the response to polysaccharide organisms has been demonstrated in those with normal splenic function, antibiotic prophylaxis can be discontinued. Patients should be monitored for evidence of endocrine dysfunction -particularly thyroid dysfunction [67]. Thyroid dysfunction occurs in up to 10% of post transplant patients.…”