Lymph node calcification secondary to chemotherapy for histiocytic lymphoma.

The fifth instance of lymph node calcification secondary to chemotherapy is reported 4 months after the onset of treatment. The recognition of the presence of such calcification is of significance because it is felt to indicate a favorable response to therapy.

Phase I trial of pentamethylmelamine in patients with previously treated malignancies.

Pentamethylmelamine (PMM), a demethylated soluble analog of hexamethylmelamine, was given to 35 patients with solid tumors in a phase I clinical trial. Thirty patients were given single doses ranging from 80 to 2000 mg/m2 in a 2-hour infusion every 3 weeks. Once a maximum tolerated dose was defined for this schedule, an additional five new patients plus four patients who had already received PMM were treated on a multiple-dose schedule of PMM given three times a week every Monday, Wednesday, and Friday (M-W-F) for 4 weeks. Dose-limiting toxic effects for the single-dose schedule were in the central nervous system and gastrointestinal tract, manifested by nausea (60%), vomiting (49%), somnolence (37%), depression (6%), and headache (6%). Other toxic effects observed on this schedule included anorexia (34%), diarrhea (7%), and diaphoresis (21%). The toxic effects were first observed in mild form at 400 mg/m2/dose and became progressively more severe and prolonged with each dose escalation; they were considered intolerable at the 2000-mg/m2 dose level in all patients treated. The nine patients receiving the multiple-dose schedule were given PMM at a dose of 1000 mg/m2 three times a week (M-W-F). This level produced dose-limited nausea and vomiting in all patients so that no patient completed greater than 3 weeks of treatment on this schedule. One patient developed PMM-related visual hallucinations. PMM produced no hematologic, hepatic, renal, allergic, or acute side effects; no alopecia was observed. Minor tumor regressions of 1 month's duration were seen in two patients, one with pleural mesothelioma and one with a parotid gland tumor. The recommended doses for solid tumor phase II studies are 1500 mg/m2 given as a 2-hour infusion every 3 weeks and 1000 mg/m2 given three times a week (M-W-F), repeated at 3-week intervals.

Phase I clinical and pharmacological study of 4'-(9-acridinylamino)-methanesulfon-m-anisidide using an intermittent biweekly schedule.

4'-(9-Acridinylamino)methanesulfon-m-anisidide (m-AMSA, NSC 249992), an acridine derivative, was given to 28 patients with solid tumors and one patient with Hodgkin's disease in a Phase I clinical trial. The dose schedule used was a single dose given every 14 days for three doses. The amount given ranged from 10 to 120 mg/sq m/dose. Dose-limiting toxicity was moderate to severe leukopenia which occurred at and above 70 mg/sq m. Thrombocytopenia was infrequent and did not require transfusion. Nonhematological side effects were mild and included nausea, vomiting, local irritation, and fever. Antineoplastic activity was noted in liposarcoma, adenocarcinoma of unknown primary origin, and squamous carcinoma of unknown primary origin (one patient each). Pharmacokinetics studies were done in 19 patients. Total m-AMSA and free m-AMSA concentrations showed a biphasic distribution with an initial rapid phase of t1/2 = 10 to 15 min for both, and a second slow phase of t1/2 = 8 to 9 hr for total m-AMSA and 3 hr for free m-AMSA. Phase II studies with m-AMSA, in hematological cancers are warranted, since its most consistent effect is on leukocytes. The recommended dosages for solid-tumor Phase II studies are 70 mg/sq m for good-risk patients and 50 mg/sq m for poor-risk patients, given as a single dose every other week, or 120 mg/sq m for poor-risk patients for the single-dose every-3-week schedule.

Abnormalities of complement and its components in patients with acute leukemia, Hodgkin's disease, and sarcoma.

Whole complement and component titers were measured in patients with acute leukemia, Hodgkin's disease, and sarcoma. Serum samples were obtained from 42 consecutive patients and 11 healthy control subjects. Sera were frozen and maintained at -70 degrees until analyzed by hemolytic assay. Titers were normalized using a titer obtained from a single source of pooled human serum analyzed simultaneously with each patient sample to correct for day-to-day variation inherent in the assay technique. Significant elevations (p less than or equal to 0.05) of whole complement and C5, C8, and C9 were observed for each patient category, compared to controls. Forty-one of 42 patients had C9 titers greater than or equal to 2 S.D. above the mean titer for controls. Mean C3 and C7 titers were not elevated or depressed in any group. No clinical factors that correlated with abnormal complement or component titers were identified.

Modulating effects of levamisole (NSC-177023) on human lymphocyte response in vitro.

Human lymphocytes were cultured in vitro with multiple concentrations of antigen, mitogen, and allogeneic cells. The addition of levamisole to stimulated cultures in concentrations of 0.03-33 mug/ml significantly amplified the response of lymphocytes to these stimuli with little or no effect on control cultures. The combination of stimulus and levamisole concentration which produced amplification was unique for each individual culture. The inconsistent results found here and elsewhere may reflect instability of levamisole under conditions of the in vitro lymphocyte culture system.

Antibody response in patients with acute nonlymphocytic leukemia.

Lymphocytotoxic (LCT) and anti-red blood cell (ABO) antibodies were measured serially in adult patients with acute nonlymphocytic leukemia (ANLL) receiving induction chemotherapy. The antigenic stimulus was provided by multiple platelet transfusions, many of which were ABO incompatible. Comparison of pretherapy titers 4-6 weeks into therapy shows that 50% (19/38) of patients became LCT positive (cytotoxicity against greater than 10% of panel of cells) and 54% (19/35) had increases in ABO titers (greater than 2 tube dilution). A total of 66% of patients had significant rises in at least one antibody. ABO and LCT titers tended to vary in parallel although exceptions were noted. The development of anti) remission rate or duration, 3) type of therapy, 4) number of platelet transfusions, 5) time relationship between the antigenic stimulus and the initiation of cytotoxic therapy, and 6) skin test reactivity. Antibody responders tended to have higher pretreatment lymphocyte counts. The ability to develop a secondary antibody response does not appear to be a major prognostic factor in ANLL.

Familial Sjögren's syndrome with associated primary salivary gland lymphoma.

Primary salivary gland lymphoma has been rarely documented in patients with or without Sjögren's syndrome. The association of disseminated lymphoreticular neoplasms with Sjögren's syndrome has been recognized, and the malignancy is usually widespread at the time of diagnosis. Familial occurrence of Sjögren's syndrome is likewise infrequently observed. In the present report we describe a patient with Sjögren's syndrome in whom a primary parotid gland lymphoma subsequently developed. In addition to the propositus, two of four siblings had definite evidence of Sjögren's syndrome and a third had several abnormal studies commonly associated with the disease. This observation suggests that genetic influence alone or in conjunction with other factors may facilitate the development of Sjögren's syndrome.

Randomized clinical comparison of daunorubicin (NSC-82151) alone with a combination of daunorubicin, cytosine arabinoside (NSC-63878), 6-thioguanine (NSC-752), and pyrimethamine (NSC-3061) for the treatment of acute nonlymphocytic leukemia.

Sixty-six newly diagnosed patients with acute nonlymphocytic leukemia received either daunorubicin alone or a combination of daunorubicin, cytosine arabinoside, 6-thioguanine, and pyrimethamine for remission-induction therapy. The two treatment groups were comparable with respect to the two major prognostic factors in this disease, which were age and presence or absence of infection on admission. The two therapies produced similar results with respect to CR rate and median survival results. Single-agent therapy was associated with less frequent utilization of hospital inpatient facilities and fewer platelet transfusions. The four-drug combination did not decrease the incidence of meningeal leukemia. Patients who achieved CR were treated with two half-dose consolidation courses of the successful remission-induction regimen. Subsequently, all patients received cyclophosphamide and guanazole monthly for maintenance therapy. Median durations of remission for both induction-treatment groups were similar (6.8 and 5.6 mos). The therapeutic results with the single agent in this study were not inferior to those obtained with the drug combination tested, as well as most other previously reported combinations of antileukemic drugs.

Abnormal profile of human nucleolytic activity as a test for cancer.

Serum samples from patients with various malignancies including acute nonlymphocytic leukemia (ANLL), brain tumor (BT), Hodgkin's disease (HD), and non Hodgkin's lymphoma (NHL) were evaluated for nucleolytic activity against six synthetic polynucleotides: polyadenylic acid, polyuridylic acid, polycytidylic acid, polyguanylic acid, polyadenylic-polyuridylic acid, and polyguanylic-polycytidylic acid; The enzyme activity was determined spectrophotometrically by following the degradation of substrate to acid-soluble nucleotides. Most patients had elevated serum RNase activity at the 95% confidence level when compared to 30 controls. Included in this group were 67% of patients with ANLL, 46% of patients with BT, 73% of patients with HD, and 67% of patients with NHL. These data confirmed the earlier suggestion that elevated serum nuclease activity is found in patients with neoplastic disease. However, whether or not a serum was identified as abnormal depended on the substrate used in the assay; this underscored the need to test samples against a variety of polynucleotides. Alterations in serum nucleolytic activity represent an important marker of neoplastic disease and can serve as the basis for a useful clinical screening device.

Combined modality therapy for localized Hodgkin's disease. A seven-year update of an early study.

Some clinical trials have indicated that combination therapy with intensive radiation therapy followed by chemotherapy significantly prolongs the disease-free interval of patients with Hodgkin's disease confined to lymph nodes. The present report updates the results of a small previously published study of combined-modality treatment of stages I and II Hodgkin's disease. Although patients tested with radiation therapy followed by chemotherapy have the longest median complete remission duration, patients treated with radiation alone have a superior survival rate. Follow-up in this study ranges from 34 to 93 months after the completion of all therapy.

A new apparatus for BCG scarification.

A procedure for administering BCG by scarification that allows for speed of application and standardization of technique was discribed.