A group of seven children with different malignant processes presenting with hypercalcemia was studied. Bone destruction, diffuse metabolic abnormalities, abnormal acid-base homeostasis and recurrent hypercalcemia characterized these patients. A different mechanism leading to the production of hypercalcemia and/or bone destruction by cancer cells is considered. The results of this report suggest that parathyroid hormone production (P.T.H.) by the parathyroid glands is normal and that ectopic secretion of PTH or PTH-like material is negligible in these cases.
I-CHOPE can induce responses in this group of patients with a poor prognosis, but most were seen in those who had previously had a response to bolus chemotherapy.
The follicular non-Hodgkin's lymphomas (NHL) have been among those tumors demonstrated to show frequent responses to alpha interferon in phase I and II clinical trials. In addition, there are data suggesting that alpha interferon demonstrates synergistic antitumor activity with alkylating agents in animal models for a number of tumors. Based on these data, Cancer and Leukemia Group B (CALGB) undertook a phase II pilot study of the combination of interferon rIFN alpha 2b (2 x 10(6) IU/m2 s.c. tiw) and cyclophosphamide (100 mg/m2 per day orally) with the ultimate purpose of examining this combination as long-term therapy of follicular lymphoma in comparison to oral cyclophosphamide alone. One hundred five advanced stage III or IV eligible patients with pathologically diagnosed International Working Formulation B or C histology were entered on CALGB 8553 to determine toxicity and response rates to the combination. Both previously chemotherapy-treated patients (32) and patients without prior chemotherapy (73) were entered on study. For patients without prior chemotherapy the overall response rate to the combination regimen was 86% with 58% of chemotherapy-treated patients achieving complete response. Chemotherapy-treated patients had a total response rate of 62% with only 25% complete responders. Complete responses in patients without prior chemotherapy were positively correlated with absence of B symptoms, and good performance status and negatively correlated with the histological subtype of follicular mixed small-cleaved and large cell histology (IWF C); only performance status was significantly correlated with response in patients who had previously had chemotherapy. Survival at 5 years is estimated to be 63% for those without chemotherapy and 39% for those previously treated with chemotherapy patients. The maximum toxicities experienced during therapy with the combination regimen of cyclophosphamide and interferon alpha were primarily related to myelosuppression. Sixty-seven percent of patients without prior chemotherapy and 65% of patients receiving prior chemotherapy experienced severe leukopenia while severe thrombocytopenia and anemia occurred in 6-31% of these patients. Non-myelosuppressive toxicities were less frequently seen. These response rates are similar to those achieved in a previous CALGB trial with oral cyclophosphamide as a single agent, although severe myelotoxicity was increased to approximately 60% of patients from less than 10% with the single-agent therapy. The combination of alpha interferon and cyclophosphamide administered in this fashion is safe when peripheral counts are carefully monitored. Randomized studies of this regimen in comparison to oral cyclophosphamide are currently in progress.
Iliac crest trephine biopsy specimens from 16 patients treated with recombinant alpha 2-interferon (alpha-IFN) for hairy cell leukemia (HCL) were examined for reticulin and collagen content. These data were compared with the hairy cell index (HCl), the proportion of hairy cells to the overall cellularity of the bone marrow. Specimens were studied immediately before alpha-IFN therapy, at 6-month intervals during, and in six patients 6 months after cessation of therapy. All patients presented with increased bone marrow fibrosis ranging from focally increased reticulin to a diffuse increase in both reticulin and collagen content. This fibrosis was observed to decrease during alpha- IFN therapy inasmuch as the hairy cell population was diminished in the bone marrow in 13 patients. Regression analysis of HCl v bone marrow fibrosis showed a positive correlation (r = .73, P less than .02). Six patients demonstrated a reduction in bone marrow reticulin and collagen to normal levels during alpha-IFN therapy. Two of six patients demonstrated increased bone marrow fibrosis and HCl 6 months after cessation of alpha-IFN therapy. Three of 16 patients exhibited no decrease in bone marrow reticulin content during therapy despite a decreased bone marrow hairy cell population.
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