Biomedical subjects
Publications and source records attributed to R Schrek.
The paper is a review of some cancer patients who were treated successfully by surgery followed by chemotherapy. The cases suggest the hypothesis that early cancer growth following surgery is more sensitive to chemotherapy than the active cancer growth of the original tumor.
The hypothesis that interferon may be useful for intractable chronic lymphocytic leukemia (CLL) is based on two incidental findings: first, the similarity in the in vitro radioresistance of the blood lymphocytes of intractable CLL and of hairy cells; secondly, the similarity of the incidence of intractable CLL patients and the incidence of CLL patients who respond to interferon treatment.
About 19-26% of patients with chronic lymphocytic leukemia (CLL) have intractable disease resistant to chemotherapy, have a relatively short median survival time and are responsive to splenectomy. Lymphocytes from patients with intractable CLL are resistant in vitro to X-irradiation and to colchicine. Responsive CLL is an accumulative disease while intractable CLL is a proliferative disease.
Lymphomas developed in mice treated with X-irradiation. The radiosensitivity of cells of the lymphomas had a bimodal frequency distribution. The cells of 11 lymphomas had approximately the same radiosensitivity as normal murine lymphocytes; 6 lymphomas were highly radioresistant. Radioresistant and radiosensitive lymphomas were analogous to intractable chronic lymphocytic leukemia (CLL) and to responsive CLL in humans. The radioresistant lymphomas can be used to study the effect of therapeutic agents on the animal model for intractable CLL both in vitro and in vivo.
About 23% of all chronic lymphocytic leukemic (CLL) patients have intractable CLL (ICLL) which is resistant to conventional therapy and has a poor prognosis. The ICLL patients complicate the determination of the efficacy of new therapeutic agents. An in vitro test is needed for the diagnosis of ICLL patients during the first examination.
About 23% of all patients with chronic lymphocytic leukemia (CLL) are resistant to chemotherapy and have intractable CLL. Recent work showed the usefulness of splenectomy for the treatment of ICLL patients. The peripheral blood lymphocytes of ICLL patients were radioresistant in vitro. This reaction provided a diagnostic test for ICLL. Normal lymphocytes are highly radiosensitive but become radioresistant on the addition of phytohemagglutinin or other mitogens. These findings suggest the hypotheses: ICLL arises from splenic lymphocytes which have reacted to an immune stimulus; ICLL is a discrete disease with its own pathogenesis, diagnosis and therapy.
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In four reported studies, intensive chemotherapy of various types was administered to large groups of patients with chronic lymphocytic leukemia (CLL) in advanced stages. About half of the patients were non-responders to the therapy. Resistance to therapy was also found in 12% of patients with early CLL and in 19 CLL patients who had in vitro radioresistant lymphocytes before therapy. The findings support the hypothesis of the heterogeneity of CLL patients and suggest the need for new methods for therapy of non-responders and for in vitro or in vivo tests to diagnose non-responders.
A significant positive correlation was obtained between the in vitro radiosensitivity of the blood lymphocytes of patients with chronic lymphocytic leukemia (CLL) and the in vivo response of the total leukocyte count subsequent to radiation therapy. Four types of equations were used to represent and measure the effect of in vitro X-irradiation on lymphocytes from CLL patients and measure the response of patients to a course of radiotherapy. For the in vivo analysis we used data from 10 patients who were routinely treated with a total of 16 courses of radiation therapy. The total leukocyte count showed a uniform exponential decline during a course of therapy. According to the literature, about 25% of all CLL patients and about 50% of CLL patients with advanced disease are resistant to chemotherapy. The equations and indices of the present study may be useful to diagnose CLL patients who are prone to be resistant to chemotherapy.
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By the method of viable lymphocyte counts, ethanol was found (1) to have a cytocidal effect on normal and leukemic lymphocytes; (2) to be more toxic to leukemic than to normal lymphocytes; (3) to be synergistic with hyperthermia, and (4) to decrease the critical temperature of normal lymphocytes from 43 to 41.5 degree C.
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We measured the effects of X-irradiation plus incubation at elevated temperatures on peripheral blood lymphocytes from normal persons and from patients with chronic lymphocytic leukaemia. Counts of viable lymphocytes were based on morphological characteristics by phase microscopy. Dose-effect curves for X-irradiation were biphasic. The D0S for lymphocytes incubated at 39 and 41 degrees were significantly less than the D0 for 37 degrees. For both normal and leukaemia lymphocytes, X-irradiation was synergistic with hyperthermia at 39 degrees and 41 degrees.
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Viable cell suspensions were prepared from 31 nodes diagnosed non-Hodgkin's malignant lymphoma, and from 30 non-malignant nodes. The cells were examined and counted by phase contrast microscopy. The suspensions were characterized by the percentage of large cells and by a colchicine-sensitivity index. The finding of more than 6% large cells or the finding of a sensitivity index of more than 30% was considered a positive test for a malignant lymphoma. According to these criteria there were 2 false positives in 30 reactive nodes and one false negative in 31 malignant nodes. Findings on 3 nodes diagnosed angioimmunoblastic lymphadenopathy suggested malignancy. The colchicinesensitivity index of blood lymphocytes seemed useful for monitoring lymphoma patients for leukemic involvement.
Forty-two patients with chronic lymphocytic leukemia (CLL) were studied for morphology of lymphocytes by light and electron microscopy (EM), in vitro responses of lymphocytes to a battery of physical and chemical agents, overall clinical status, immunologic status, course, and response to therapy. CLL lymphocytes could be classified by EM into four groups on the basis of cell size and nuclear contour and by light microscopy into two groups, small cells and large cells (lymphosarcoma cells). Patient survival did not vary with cell size or morphology as determined by light or electron microscopy. In vitro testing of CLL lymphocytes following exposure to X-ray, PHA, DMSO 2 hr at 43 degrees C, prednisolone, glutaminase, and asparaginase permitted a separation of patients into categories of normal and abnormal in vitro responses. A normal in vitro response predicted a good response to therapy but an abnormal in vitro response did not preclude a good response to therapy. Following therapy, normalization of abnormal EM morphology and in vitro response was seen in some patients. Most patients tested had decreased serum immunoglobulins and abnormal PHA responses. There was a high incidence of infections and second neoplasms. Immunologic deficits could not be correlated with variations in lymphocyte morphology or in vitro response.
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