Response to "Unrelated agranulocytosis in a patient taking clozapine".
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Agranulocytosis↗
Biomedical subjects
K Rai
Publications and source records attributed to K Rai.
2-Chlorodeoxyadenosine is an active salvage therapy in advanced indolent non-Hodgkin's lymphoma.
PURPOSE: To determine the response rate to 2-chlorodeoxyadenosine (2-CdA; cladribine) in patients with advanced indolent non-Hodgkin's lymphoma (NHL) who fail to respond to or progress after a response to standard chemotherapy drugs. PATIENTS AND METHODS: Twenty-one patients were treated with at least one cycle of 2-CdA 0.1 mg/kg/d by continuous infusion for 5 or 7 days. RESULTS: The overall response rate (complete response [CR] and partial response [PR]) was nine of 21 patients (43%; 95% confidence interval, 22% to 64%). Unmaintained durable responses (longest follow-up, 29+ months) have been observed. The treatment was well tolerated by all patients. The major toxicity was related to myelosuppression (predominantly neutropenia) and immunosuppression with infection. CONCLUSION: The purine analog 2-CdA is an active salvage therapy in pretreated patients with indolent NHL, and deserves further assessment in untreated patients and in combination with other chemotherapy agents.
Adolescent↗
Thrombocytopenia in association with adjunctive felbamate use.
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Adult↗
Recent progress in chronic lymphocytic leukemia. International Workshop on chronic Lymphocytic Leukemia.
The data we discuss indicate substantial recent progress in understanding and treating CLL. However, despite considerable new information, many of the intriguing issues we posed at previous IWCLL meetings remain unanswered. Prominent among these are the questions of what causes CLL, what is the relation between CLL and normal B-cell development, are T-cell abnormalities a cause of consequence of CLL, why are auto-immune features so prominent and how is CLL best treated? Although these gaps in our knowledge are unfortunate, they give us the opportunity for yet another IWCLL meeting: 1996 in Greece. More to follow.
Antigens, CD↗
Prolonged subcutaneous administration of recombinant alpha 2b interferon in patients with previously untreated Philadelphia chromosome-positive chronic-phase chronic myelogenous leukemia: effect on remission duration and survival: Cancer and Leukemia Group B study 8583.
We investigated whether recombinant alpha 2b interferon (r alpha 2bIFN) would reduce the proportion of bone marrow Philadelphia chromosome (Ph) cells in chronic-phase chronic myelogenous leukemia (CML) by treating 107 previously untreated patients daily with r alpha 2bIFN at 5 x 10(6)IU/m2 subcutaneously. Patients with complete remission, partial remission, or partial hematologic remission received treatment until progression; those with progressive disease were taken off study and observed for survival. Sixty-three (59%) of the patients achieved at least a partial hematologic remission (24 complete remissions and 39 partial remissions). The median time to response for the 63 responders was 3.4 months, with a median duration of remission of 52 months and with 81% of responders continuing in remission beyond 12 months. The median survival for the 107 patients was 66 months. Of 78 patients with cytogenetic follow-up data, 31 (40%) achieved a partial cytogenetic response (n = 17) or a complete cytogenetic response (n = 14). The percentage of cytogenetic responders among all patients was 29% (31 of 107 patients). The median time to first cytogenetic response was 9 months. A major dose reduction of r alpha 2bIFN (> or = 50%) was required at some time during treatment in 38% of patients, 26% required 10% to 49% dose reductions, and 36% had minor dose reductions of < or = 10%. No association was observed between dose received and the attainment of a cytogenetic response. None of the usual prognostic factors (sex, race, performance status, weight loss, time from diagnosis to treatment, hepatosplenomegaly, age, symptoms, hemoglobin, or platelet, blast, basophil, or white blood cell count) were significantly related to survival. These data provide confirmation that major cytogenetic responses to prolonged administration of subcutaneous r alpha 2bIFN occur in 20% to 38% (95% confidence interval) of chronic-phase Ph-positive patients. Although it is hypothesized that patients achieving major cytogenetic responses to r alpha 2bIFN should have prolonged remission duration and survival compared with nonresponders, analyses of the effect of cytogenetic responders by both "landmark" and time-dependent covariate techniques fail to provide statistically significant evidence for an effect of cytogenetic response on remission duration or survival. This may be due in part to an effect size insufficiently large to be detected with the number of patients treated in this study. Thus, confirmation of remission duration or survival benefit, if any, of r alpha 2bIFN therapy in Ph-positive chronic-phase CML must await the outcome of randomized trials comparing IFN with conventional agents.
Adolescent↗
Unrelated agranulocytosis in a patient taking clozapine.
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Agranulocytosis↗
Hyperamylasemia and hematologic malignancies.
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Adult↗
The frequency of long-term remission in patients with acute myelogenous leukaemia treated with conventional maintenance chemotherapy: a study of 760 patients with a minimal follow-up time of 6 years.
Remission duration associated with the administration of conventional maintenance chemotherapy to patients with acute myelogenous leukaemia was evaluated. The records of 760 patients who entered remission between 1974 and 1979 were reviewed. The median duration of remission was 1.1 years with 16% of patients remaining in remission at 8 years. The relapse curve was biphasic with a high rate of relapse during the first 2 1/2 years of remission followed by a much lower relapse rate thereafter. Leukaemic relapses were noted through 8 years of remission. A plateau phase indicating freedom from the risk of leukaemic recurrence is not clearly apparent yet but may exist after the eighth year of remission.
Adult↗
Clozapine-induced agranulocytosis: non-cross-reactivity with other psychotropic drugs.
Clozapine, an atypical neuroleptic with unique clinical and preclinical properties, represents a potentially valuable addition to the psychopharmacopeia. Its development and use have been limited by its higher frequency, compared with other pharmacologic treatments, of the potentially fatal side effect of agranulocytosis. This article describes the natural history of five cases of agranulocytosis that occurred in the course of clozapine treatment. The cases were generally uniform as to onset, recovery, and hematologic features. No patient had hematologic reactions to treatment with psychotropic agents before or after clozapine treatment. These findings, along with other work in progress, suggest that clozapine's granulocytoxic effects are produced by a highly specific immune-mediated mechanism.
Adult↗
Inter and intraspecific variation in nuclear DNA content in Aedes mosquitoes.
Haploid nuclear DNA of 23 species of Aedes, as determined by Feulgen cytophotometry, was found to vary 3-fold. This was accompanied by a 2-fold variation in total chromosomal length. There was a significant correlation (r = 0.765, P less than 0.001) between these two parameters. Genome size varied from 0.87 pg to 1.3 pg among 10 strains of Aedes albopictus, from wide geographic regions. Large scale differences in chromosomal DNA amounts have accompanied speciation and evolution in aedine mosquitoes.
Aedes↗
A dose-response model incorporating nonlinear kinetics.
This paper introduces a dose-response model for toxic quantal response data based on hit theory applied to the dose unit as transformed by a nonlinear kinetic equation. When spontaneous background response is included in the model, the resulting dose-response model has four parameters. The maximum likelihood estimators and their large-sample properties are given. Likelihood ratio tests of interest are developed, including one for whether the model is one-hit in the transformed dose and one to check whether nonlinear kinetics is operative. The use of the model for low-dose extrapolation is presented. Finally, the procedures developed are illustrated on data from three animal carcinogenicity bioassays that show, respectively, concave, linear, and convex dose-response curves in the observed data.
Animals↗
Randomized trial of high-dose cytarabine versus amsacrine in acute myelogenous leukemia in relapse: a Leukemia Intergroup Study.
Patients with acute myelogenous leukemia in relapse who were ineligible for further anthracycline therapy either because they were judged to be anthracycline resistant or had received the maximum doses were randomized to receive high-dose cytarabine (3 g/m2 every 12 hours for 6 days) or amsacrine (75 mg/m2 daily for 7 days). The response rates in both groups were similar: three of 25 patients given high-dose cytarabine and three of 23 given amsacrine obtained complete remissions.
Adolescent↗
Yaws in Indonesia.
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Health Services Accessibility↗
Treatment of patients with acute nonlymphocytic leukemia in relapse: a Leukemia Intergroup study.
Forty patients with acute nonlymphocytic leukemia (ANLL) in first relapse were treated at eight member institutions of the Leukemia Intergroup with a 10-day continuous intravenous infusion of cytosine arabinoside and an anthracycline antibiotic administered on days 1, 2, and 3. Twenty of the 40 patients achieved a complete response. Seven of the patients who did not enter remission were drug-resistant failures, while 13 patients failed to enter remission for reasons other than persistent leukemia. Pretreatment parameters such as age, presence of infection, platelet count, and liver function tests were important predictors of survival. The percent bone marrow cellularity, the percent circulating abnormal (leukemic) cells, and the height of the white blood cell count prior to treatment were helpful in distinguishing patients who would enter remission from those who would not enter remission because of persistent leukemia.
Adolescent↗
Plasminogen-dependent fibrinolytic activity in normal human lymphocytes: diminished lymphocyte plasminogen activator in chronic lymphocytic leukemia.
Discrepancies in correlations between fibrinolytic activity and metastatic potential of malignant cells has resulted in speculation on the putative role of plasminogen activators (PA) in cancer. In this report we have compared lymphocyte PA from 40 patients with chronic lymphocytic leukemia (CLL) to normal human B- and T-lymphocytes. Lymphocytes were isolated from peripheral blood by Ficoll-Hypaque centrifugation. The B- and T-cells were further separated on nylon wool columns. Cell PA activity and cell membrane PA were determined using 3H-fibrin-coated plates with added human plasminogen. Lymphocytes did not lyse 3H-fibrin in the absence of plasminogen. Plasminogen-dependent fibrinolytic activities of normal B- and T-lymphocytes were comparable. The addition of protease inhibitors with trypsin or plasmin specificity to lymphocytes significantly inhibited normal PA, thus substantiating the serine protease spectrum of lymphocyte PA. Examination of lymphocytes from greater than 95% of patients with chronic lymphocytic leukemia revealed a marked decrease in lymphocyte and cell membrane PA as compared to normals. No correlation between Stage of CLL and lymphocyte PA was observed. Likewise, an inhibitor of PA in CLL lymphocytes was not detected. The function of PA in normal B-lymphocyte physiology and the potential pathogenetic role of diminished PA in CLL lymphocytes remain to be explored.
Fibrinolysis↗
A dose-response model for teratological experiments involving quantal responses.
This paper introduces a dose-response model for teratological quantal response data where the probability of response for an offspring from a female at a given dose varies with the litter size. The maximum likelihood estimators for the parameters of the model are given as the solution of a nonlinear iterative algorithm. Two methods of low-dose extrapolation are presented, one based on the litter size distribution and the other a conservative method. The resulting procedures are then applied to a teratological data set from the literature.
Abnormalities, Drug-Induced↗
Prediction of response of acute nonlymphocytic leukaemia to therapy with 'high dose' cytosine arabinoside.
The Leukemia Intergroup Study has treated 110 patients with acute nonlymphocytic leukaemia with 'high dose' cytosine arabinoside remission induction therapy and studied the factors which were related to the outcome of therapy. With respect to death during remission induction therapy, only patient age was of prognostic significance. Treatment failure due to resistant leukaemia was associated with a high pretherapy leukaemic cell mass, the presence of few cells in S phase, and insensitivity of DNA synthesis to cytosine arabinoside. If, after 6 d of therapy, more than 40% of the marrow cells were leukaemic, the patient almost invariably failed to enter complete remission because of persistent leukaemia. Simultaneous consideration of the pretherapy labelling index and the per cent abnormal cells in the day 6 marrow permitted a distinction to be made between almost all patients who would enter remission or fail therapy because of persistent leukaemia.
Age Factors↗
Changes in body composition of cancer patients following combined nutritional support.
The effects of combined nutritional support (parenteral, enteral, and oral) were measured in cancer patients unable to maintain normal alimentation. Changes in body composition were quantified by measurement of total body levels of nitrogen, potassium, water, and fat. The protein-calorie intake of the patients was also evaluated by dietary survey (4-day recall). Standard anthropometric and biochemical measurements for nutritional assessment were obtained for comparison. The dietary evaluation indicated that the dietary supplementation for all patients was more than adequate to meet their energy requirements. Almost all patients gained weight on the combined nutritional support regimens. Determination of body composition indicated that change in body weight was equal to the sum of the changes in body protein, total body water, and total body fat. The findings from the anthropometric nutrition indices (arm muscle circumference and triceps skinfold) were consistent with the results of the body composition study. Information on the nature of the tissue gained was obtained by comparison of body composition data with the ratio of protein:water:lean body mass for normal tissue. The mean gain of protein in the cancer patients was quite small (0.3-0.6 kg). The main change in body weight appeared to be the result of gains in body water and body fat. The total body nitrogen to potassium ratio served to define the extent of tissue anabolism following hyperalimentation. The ratio dropped in the cancer patients following hyperalimentation toward the value of the control subjects on ad libidum diets. The body compartment techniques described have demonstrated their usefulness in determining the effects of hyperalimentation on cancer patients.
Adipose Tissue↗