Richard I. Fisher

Diffuse histiocytic lymphoma involving the gastrointestinal tract

The results of staging and treatment of 18 patients with diffuse histiocytic lymphoma involving the gastrointestinal tract are summarized. Widespread disease (Stage IV) was found in the majority (72%) of patients after rigorous staging, indicating the relative rarity of localized gastrointestinal lymphoma and the resulting need for systemic therapy in most of these patients. Chemotherapy combined with surgical resection and/or radiation therapy produced complete remissions in only 5 of 18 patients (28%). Patients failed to achieve complete remission due to 1) tumor resistance to drug therapy (46% of treatment failures), and 2) massive intestinal hemorrhage or bowel perforation secondary to tumor necrosis (38% of treatment failures). These finding indicate the need for more active chemotherapeutic regimens and for measures aimed at preventing complications such as bowel perforation or hemorrhage, possibly by combining surgical resection of bowel lesions with systemic chemotherapy.

HEXAMETHYLMELAMINE IN ALKYLATING AGENT-RESISTANT OVARIAN CARCINOMA

Twenty‐one patients with advanced ovarian cancer proven resistant to standard alkylating chemotherapy were evaluated in a prospective study of Hexamethylmelamine. All but three patients received 8 mg/kg daily with dose modifications appropriate to the degree of toxicity; the latter three patients were treated on an intermittent 14 day course of 8 mg/kg daily. Six patients (28%) experienced an objective response with a median duration of 2.5 months (range 1—5 months). The toxic effects requiring dose modification were gastrointestinal in 57%, hematologic in 62%, and neurologic in 28.5%. An average of 60.5% of the total projected dose was tolerated for a median of 44 days (range 7‐113). Twelve patients (57%) experienced severe toxicity requiring discontinuation of therapy. It is apparent from this study that Hexamethylmelamine is an active agent in ovarian cancer and is not invariably cross‐resistant to conventional alkylating agent therapy. These two characteristics make it an attractive agent for use in combination. Its toxicity in previously treated patients in the schedules used here, however, is substantial. Cancer 42:2157–2161, 1978.

Natural history of malignant lymphomas with divergent histologies at staging evaluation

The pathology and medical records of 515 patients with malignant lymphomas treated at the National Cancer Institute have been reviewed to determine the frequency and natural history of patients who have different histologic diagnoses in various tissue sites at their initial staging evaluation. Of the 101 patients who had multiple tissue sites biopsied, 33 patients had different histologic diagnoses. Eighteen patients had a nodular pattern in one site and a diffuse pattern in another. The final stage and treatment of these 18 patients were similar to that of the 27 patients with multiple identical nodular biopsies and 41 patients with multiple identical diffuse biopsies. However, the 56% complete response rate for patients with both a nodular pattern and a diffuse pattern was intermediate between that achieved in patients with identical nodular biopsies (70%) and identical diffuse biopsies (30%). Median survival for these three groups was as follows: identical nodular biopsies, 53 months; both a nodular and a diffuse pattern, 37 months; and identical diffuse biopsies, 12 months. These results demonstrate that patients with different histologic diagnoses in various sites at staging evaluation are not uncommon and have a unique natural history that should be considered in planning treatment.

Reduced concentrations of the first component of complement in hypogammaglobulinemia: Correction by infusion of γ-globulin

Abstract The first component of complement (C1) is a macromolecular protein with three well-characterized subunits, q, r, and s. Patients with hypogammaglobulinemia have variably reduced hemolytic concentrations of C1, which is secondary to a selective reduction in the immunoglobulin (Ig) binding subunit, C1q. On four occasions a C1-free Ig preparation was infused into a patient with hypogammaglobulinemia. C1q and C1s levels showed a marked increase in the 24 hr following the rise in IgG. The data add further support to the proposal that decreased C1q levels in these patients are not secondary to reduced synthesis but represent an increased catabolic rate in the absence of normal plasma IgG levels. Weak, reversible interactions between C1q and Ig play an important role in maintaining intravascular serum C1q concentrations.

Treatment of diffuse large cell non-Hodgkin’s lymphomas

Advanced stages of diffuse mixed lymphoma, diffuse histiocytic or large cell lymphoma, and diffuse undifferentiated non-Burkitt’s lymphoma have traditionally been considered rapidly progressive, fatal diseases. During the 1960s, few of these patients survived for five years [1]. In 1975, it became apparent that combination chemotherapy could achieve long-term disease-free survival in advanced diffuse histiocytic lymphoma [2]. This observation was confirmed soon thereafter [3–6] and, by 1977, it was established that complete remissions, documented by re-evaluation of all initially involved sites, could be obtained in approximately 40–50% of these patients, and that 75–80% of the complete responders would have long-term disease-free survival. In 1983, results of the ProMACE-MOPP treatment program suggested further improvement in these therapeutic results [7]. Several other studies also indicated significantly prolonged survival [8–10]. At present, long-term disease-free survival may be achieved in approximately 60% of all patients with advanced stages of diffuse aggressive lymphomas.