Pediatric Hodgkin's disease: pulmonary, cardiac, and thyroid function following combined modality therapy

Abstract

Since pediatric Hodgkin's disease is a curable malignancy, it is essential to limit treatment sequelae. This study examines post-treatment pulmonary, cardiac, and thyroid function in 34 children, ages 5 to 17 (23 male and 11 female) with Hodgkin's disease. All received combined modality therapy of 6 cycles of alternating ABVD/MOPP chemotherapy and low dose (1500-2500 cGy) involved field radiotherapy. Mean follow-up period is 27.5 months with actuarial freedom from relapse of 94% and survival of 92%. Twenty asymptomatic patients underwent pulmonary function testing following chemotherapy and supradiaphragmatic radiotherapy. Eleven patients had post-treatment carbon monoxide diffusing capacity (DLCO) performed. Six of 11 children (55%) had abnormal values (mean 66%, range 58-80) showing either a reduced DLCO compared to pretreatment or an low absolute value. Eight of the twenty patients (40%) tested post-treatment for FEV1, FVC, TLC and flow volume loop had abnormal results. Six showed restrictive abnormalities and two had obstructive dysfunction. Fourteen patients underwent cardiac nuclear gated angiogram after completion of chemotherapy. Two asymptomatic patients (14%) had abnormal scans showing either a low resting ejection fraction or a decreased response to exercise. Thyroid function was evaluated post-treatment in twenty-one patients by TSH, T4, free T4 or sensitive TSH analysis. Four (21%) had an elevated TSH with a normal T4 after treatment. Although post-treatment thyroid and cardiac effects were minimal, post-treatment pulmonary dysfunction in asymptomatic patients was substantial with more than 50% of tested children demonstrating an abnormal DLCO and 40% showing restrictive or obstructive pulmonary parameters. These abnormalities were observed following a maximum bleomycin dose of 60 units/m2. Bleomycin and pulmonary radiotherapy have adverse effects on diffusing capacity and the long-term pulmonary sequlae of combined ABVD chemotherapy and radiotherapy are unknown. Our analysis suggests that even in asymptomatic children, pulmonary abnormalities are frequent.