Interleukin-6-associated laboratory parameters and immunohistochemistry in symptomatic stage A and B nodular sclerosing Hodgkin's disease in children.

Interleukin (IL)-6-associated laboratory parameters obtained at diagnosis on 17 children with histologically confirmed nodular sclerosing Hodgkin's disease (NSHD) are reported. When these patients were grouped as either symptomatic stage A or B, they were found to be similar in extent of disease, age, and gender. However, statistically significant differences between these two groups were observed for the means of the following IL-6-associated laboratory parameters: hematocrit (p = 0.019), platelet count (p = 0.009), serum albumin (p = 0.001), and ferritin (p = 0.037) concentrations. Moreover, trend analysis of abnormalcy revealed an increasing frequency of anemia, thrombocytosis, hypoalbuminemia, and hyperferritinemia between stage A and B patients and, when available, febrile controls (p values = 0.0012, 0.0009, 0.0406, and 0.0011, respectively). Correspondingly, IL-6 immunohistochemistry performed on archival material from representative cases in each group showed greater overall reactivity in specimens from stage B patients. A variety of cells accounted for this positivity for IL-6 antigen including Reed-Sternberg cells and their variants, lacunar cells, dendritic interdigitating cells, endothelial cells, fibroblasts, and vascular smooth muscle cells. In summary, greater and more frequent abnormalities in IL-6-associated laboratory parameters and increased immunohistochemical reactivity for IL-6 antigen coincide with the presence of fever in helping to identify children with clinical stage B NSHD.

Phase I clinical trial with floxuridine and high-dose continuous infusion of leucovorin calcium.

Sixty-two patients with metastatic disease were treated with continuous infusion folinic acid (leucovorin calcium; Lv) and 2-deoxy-5-fluorouridine (floxuridine; FUDR). Lv was given by constant intravenous (IV) infusion at 500 mg/m2/d, days 1 to 6, while FUDR was given by IV push, days 2 to 6, at 3:00 PM daily with doses ranging from 294 to 1,214 mg/m2/d. This program was well tolerated with dose-limiting toxicities of diarrhea and stomatitis, while hematologic toxicity was minimal. Eighty-two percent of the assessable patients (46 of 56) had failed at least one chemotherapy regimen. One complete remission lasting 9 months and 10 partial remissions ranging from 5 to 10 months were observed in this heavily pretreated patient population for an overall response rate of 20%. These data suggest that the combination therapy with Lv and FUDR may have clinical use. Because of differing patient sensitivity to this drug combination, the recommended dose of FUDR for the initial therapy cycle is 500 mg/m2/d, days 2 to 6, with subsequent escalation to 900 mg/m2/d in those patients without extreme sensitivity. Phase II studies are now in progress with these doses.