Earl N. Metz

Superiority of adriamycin‐containing combination chemotherapy in the treatment of diffuse lymphoma. A southwest oncology group study

As a part of an ongoing prospective controlled trial, the Southwest Oncology Group compared the results of treatment of advanced non‐Hodgkins lymphoma with two CHOP regimens (cyclophosphamide, adriamycin, vincristine and prednisone with either low‐dose bleomycin or BCG by scarification) to a COP regimen (cyclophosphamide, vincristine and prednisone) with low‐dose bleomycin (COP‐Bleo). The study design emphasized histopathology review and systematic restaging to define complete remission (CR). Confirmed rates of CR for 443 evaluable patients were 59% for 286 patients receiving the CHOP regimens and 59% for 157 patients receiving COP‐Bleo. Rates of CR were higher for patients with nodular lymphoma (69%) compared to those with diffuse lymphoma (54%) (p = 0.005). For patients with nodular lymphoma there was no difference in CR rates according to treatment. For patients with diffuse lymphomas the CR rate was higher with the CHOP programs (58%) than with COP‐Bleo (44%) (p = 0.10). Overall duration of CR and survival was significantly longer for patients with nodular lymphoma compared to diffuse lymphoma (p < 0.01). At this time, remission duration and survival were similar regardless of induction regimen used in patients with nodular lymphoma. However, in patients with diffuse lymphoma, the duration of CR and overall survival were improved by treatment with the CHOP regimens compared to COP‐Bleo (p = 0.02). Thus, in this controlled study we have demonstrated that initial combination chemotherapy employing the CHOP regimen was a superior remission induction therapy for patients with diffuse lymphoma. Cancer 43:417–425, 1979.

Leukemic reticuloendotheliosis: A study of the origin of the malignant cell

A highly pure preparation of neoplastic cells from the spleen of a patient with leukemic reticuloendotheliosis was studied for function, membrane characteristics and glucose metabolism. Glass adherence and phagocytosis of small particles (latex and carbon black) were demonstrated with phase contrast microscopy. Staphylocidal activity was similar to that of normal monocytes. Immunofluorescent assays revealed nonspecific uptake of antiserums to immunoglobulins G (IgG), M (IgM), A (IgA) and kappa and kappa and lambda light chains. Rosette assays indicated the presence of receptors for IgG on the surface of all cells but no receptors for complement (C3) or sheep red blood cells. Glucose metabolic studies revealed a pattern that differed from that of normal monocytes or lymphocytes with intermediate values for glycolysis, low hexose monophosphate shunt activity and high Krebs cycle activity. Increments in tritiated (3H)-thymidine uptake and glucose metabolism in response to phytohemagglutinin stimulation were minimal (5 per cent of normal lymphocyte values) and no response was noted with pokeweed mitogen stimulation. These findings suggest that the leukemic reticuloendotheliosis cell most closely resembles cells of the monocyte-histiocyte series.

Improved complete remission rates and survival for patients with large cell lymphoma treated with chemoimmunotherapy: A southwest oncology group study

Between 1974 and 1977, 652 patients with non‐Hodgkins lymphoma without prior chemotherapy were randomized to 1 of 3 combination chemotherapy programs designed to induce complete remission (CR): COP‐bleomycin (180 patients), CHOP‐bleomycin (232 patients) or CHOP plus immunotherapy with Bacillus Calmette Guerin (BCG) (240 patients). With mature follow‐up, the major effect of BCG immunotherapy was observed in patients with large cell lymphomas (diffuse or nodular “histiocytic”) and not in other common lymphoma subtypes. CR rate for 65 patients with large cell lymphoma treated with CHOP‐BCG was 68% compared to 48% in 61 patients treated with CHOP‐bleomycin (P = 0.02) (two‐tailed test) or 44% for 45 patients treated with COP‐bleomycin (P = 0.02). CR duration for both CHOP‐based regimens was similar and superior to that produced by COP‐bleomycin (P = 0.03). Survival of patients with large cell lymphoma treated with CHOP‐BCG was better than that observed with CHOP‐bleomycin (P = 0.02) or COP‐Bleomycin (P = 0.002). Although the explanation for the favorable effect of BCG remains unclear, further clinical trials to evaluate the combination of chemotherapy and other “biologic response modifiers” is warranted for patients with lymphoma.

Pulmonary embolism as a result of Hickman catheter-related thrombosis

S ince their introduction in the 197Os, Hickman catheters and similar venous access devices have become widely used in the management of patients with cancer [l-5] because of the ease they confer on blood drawing and administration of intravenous medications, nutrition, and hydration. As with other intravascular foreign objects, the complications of infection and thrombosis have been encountered but have in general been readily managed [6]. Adequate management requires prompt diagnosis for which a high index of suspicion is needed. Two cases of pulmonary embolism from superior vena caval thrombosis due to a Hickman catheter seen by the authors during a recent two-month period emphasize that this complication is not rare. These cases are presented with a review of the literature reporting thrombosis and pulmonary embolism due to Hickman catheters and similar venous access devices.

Transfer factor: Isolation of a biologically active component☆

Abstract The chromatographie separation of transfer factor from a tuberculin-sensitive donor resulted in isolation of a fraction which was proved to be active by both local and systemic transfer of the specific immunity present in the donor. This isolation technique may lead to the ultimate characterization of transfer factor.

The effect of transfer factor therapy on tumor immunity in alveolar soft part sarcoma

Abstract A young man with alveolar soft part sarcoma and his identical twin were studied in terms of immunologic response to the patients tumor homogenate. The lymphocytes from both twins underwent lymphoblastic transformation to tumor homogenate but only the healthy twins lymphocytes released demonstrable migration inhibition factor (MIF) to the tumor preparation. Transfer factor was prepared from the healthy twin and administered to the tumor-bearing twin. A total dose of transfer factor equivalent to 45 × 10 8 lymphocytes given in three separate doses produced a persistently positive MIF assay in the patient. The tumor neither regressed nor progressed during the 6-month period after transfer factor therapy.

Effect of inorganic phosphate on erythrocyte pentose phosphate pathway activity

1. 1. Pentose phosphate pathway activity was studied in human erythrocytes during incubation with inorganic phosphate (Pi). The rate of 14CO2 production from labelled glucose was used as an index of pentose phosphate pathway activity and was measured continuously with an ionization chamber and vibrating reed electrometer. 2. 2. In unstimulated erythrocyte suspensions, pentose phosphate pathway activity was unaltered by a Pi concentration which increased the rate of glucose consumption. Red cells incubated with both Pi and methylene blue showed increased CO2 production from [I-14C]glucose and decreased CO2 from [2-14C]glucose compared with controls. 3. 3. Total pentose phosphate pathway activity, as indicated by the sum of CO2 production from [I-14C]glucose and [2-14C]glucose or by CO2 production from uniformly labelled glucose, was unaltered. These results suggests that Pi can reduce the activity of transketolase or transaldolase in intact erythrocytes.

Acute myelomonocytic leukemia with macroglobulinemia, bence jones proteinuria, and hypercalcemia

A patient presenting with the unusual combination of acute myelomonocytic leukemia, monoclonal macroglobulinemia, Bence Jones proteinuria and hypercalcemia is discussed. Remission of the acute leukemia was associated with clearing of the other problems. Although concurrent multiple myeloma or Waldenstroms macroglobulinemia cannot be completely excluded the possibility of this constellation of findings representing synthetic activity of the acute leukemic myeloblast is suggested.

Coumarin necrosis of the penis.

Coumarin-induced necrosis of the skin and subcutaneous tissue is an uncommon but well recognized complication of anticoagulant therapy. Although any area of skin may be involved necrosis of the penis is rare. We report a case of penile necrosis associated with coumarin therapy and review the literature.

Studies on the Ability of Stored Blood to Transport Oxygen In Vivo

Blood stored in acid-citrate-dextrose (ACD) shows a progressive increase in oxygen affinity primarily as the result of a decrease in red cell 2,3-diphosphoglycerate (DPG)1. Restoration of DPG levels (and presumably normal blood oxygen affinity) appears to occur promptly after transfusion of ACD-stored, DPG- depleted blood. Delayed restoration of DPG and oxygen affinity may impair oxygen delivery. Beutler and Wood reported that DPG values returned to nearly 50 percent of normal within 4 hours.2 Others have indicated that at least 25 percent of the final DPG level was achieved within 8 hours after completion of transfusion.3 Whether the rate of DPG restoration is significantly variable from patient to patient is uncertain because only a few patients have been reported.