ABSTRACT
BACKGROUND: Vascular-related toxicities have been reported among survivors of Hodgkin lymphoma (HL), but their genesis is not well understood. PROCEDURE: Fasting blood samples from 25 previously irradiated HL survivors were analyzed for biomarkers that can reveal underlying inflammation and/or endothelial cell activation: high-sensitivity C-reactive protein (hsCRP), triglycerides, total cholesterol, high-density lipoprotein (HDL), apolipoprotein ß, lipoprotein (a), fibrinogen, circulating endothelial cells (CECs), and vascular cell adhesion molecule-1 (VCAM-1) expression. Values were compared to subjects in the Coronary Artery Risk Development in Young Adults (CARDIA) study. CECs and VCAM-1 were compared to healthy controls. RESULTS: Survivors (76% male), median age 17.6 years (5-33) at diagnosis, 33.0 years (19-55) at follow-up, included stages IA (n = 6), IIA (n = 10), IIB (n = 2), IIIA (n = 4), and IVA (n = 3) patients. Twenty-four received at least chest radiation therapy (RT) (median dose 3,150 cGy; range: 175-4,650 cGy), one received neck only; 14 (56%) had a history of anthracycline exposure (median dose: 124 mg/m(2) range: 63-200 mg/m2). Compared to CARDIA subjects, mean hsCRP (3.0 mg/L ± 2.0 vs. 1.6 ± 1.9), total cholesterol (194.1 mg/dl ± 33.2 vs. 179.4 ± 32.9), lipoprotein (a) (34.2 mg/dl ± 17.5 vs. 13.8 ± 17.5), and fibrinogen (342.0 mg/dl ± 49.1 vs. 252.6 ± 48.4) were significantly elevated. CECs (2.3 cells/ml ± 1.5 vs. 0.34 ± 1.4) were significantly elevated compared to controls. No difference in VCAM-1 expression (51.1% ± 36.8 vs. 42.3 ± 35.6) was detected. CONCLUSION: HL survivors exposed to RT have evidence of vascular inflammation, dyslipidemia, and injury suggestive of early atherogenesis.
Subject(s)
Biomarkers/blood , Hodgkin Disease/complications , Hodgkin Disease/mortality , Survivors , Vascular Diseases/etiology , Vascular Diseases/mortality , Adolescent , Adult , C-Reactive Protein/metabolism , Case-Control Studies , Child , Child, Preschool , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Female , Fibrinogen/metabolism , Follow-Up Studies , Hodgkin Disease/radiotherapy , Humans , Inflammation/blood , Inflammation/etiology , Inflammation/mortality , Lipoprotein(a)/blood , Male , Middle Aged , Neoplasm Staging , Pilot Projects , Radiotherapy Dosage , Survival Rate , Triglycerides/blood , Vascular Cell Adhesion Molecule-1/blood , Vascular Diseases/blood , Young AdultABSTRACT
Toxic leukoencephalopathy syndromes are rare disorders of cerebral injury characterized by changes in the white matter and accompanying neurologic dysfunction. They have been reported in association with a variety of clinical etiologies, most commonly including severe hypertension, cranial irradiation, and environmental toxins. However, they have also been described in conjunction with immunosuppressive and chemotherapeutic agents. There has been one case of fatal leukoencephalopathy reported following CHOP chemotherapy for non-Hodgkin lymphoma. We report a second case of fatal necrotizing leukoencephalopathy following the administration of CHOP chemotherapy.
