Search PubMed⌕ Search

Biomedical subjects

K R Rai

Publications and source records attributed to K R Rai.

At least 55 records · Page 3Linked to original sources
PubMed1987

A review of the prognostic role of cytogenetic, phenotypic, morphologic, and immune function characteristics in chronic lymphocytic leukemia.

Recent reports of successfully completed cytogenetic studies using polyclonal B-cell activators demonstrate that trisomy-12 and 14 q+ are the most frequently observed chromosomal abnormalities in B-cell chronic lymphocytic leukemia (CLL). It appears that when trisomy-12 is accompanied by yet another abnormality, the prognosis of patients is uniformly poor. Patients in early stages of CLL retain delayed hypersensitivity reactivity, while those in advanced stages are usually anergic. The lymphocytes from venous blood of patients with CLL appear to retain at least some ability to respond to stimulation with mitogens in early stages, whereas in advanced stages they show no response to mitogens. Serum immunoglobulin levels are normal in the early (0 and I) stages, are markedly decreased in the advanced (III and IV) stages, and are somewhat between these extremes in the intermediate (II) stage of CLL. Prolymphocytic leukemia and prolymphocytoid transformation of CLL are indicators of poor prognosis, while a morphological variant characterized by large granular lymphocyte is associated with good prognosis. At this time it is not possible to ascribe strong prognostic significance to phenotypic features of lymphocytes in B-CLL; however, studies currently in progress may soon provide important insights on this subject. We have reviewed the pertinent literature and we also present a summary of results from our laboratory.

Chromosome Aberrations↗
PubMed1987

Prognostic factors in chronic lymphocytic leukemia.

The Rai staging system is widely used and is easy to apply in clinical practice. The system introduced by Binet et al offers an advantage that it consists only of three stages and, therefore, is more practical for initiation of controlled therapeutic trials than the five-stage Rai system. However, when we take into consideration the survival curves, it is important to note that the Rai system has three groups (and not five), low risk (stage O), intermediate risk (stages I and II), and high risk (stages III and IV). These groups are roughly equivalent to Binet's A, B, and C stages, respectively. Although the IWCLL has recommended a unified, integrated method of combining Binet and Rai systems, in practice, however, such a combination is cumbersome and unusable. Both systems, however, suffer from an important limitation--they cannot predict for the large majority of patients in the low and intermediate risk groups (Binet's stages A and B and Rai's O, I, and II) who will have an indolent course and good prognosis in contrast to those in the same stages whose disease will progress rapidly. It is necessary, therefore, to combine the bone marrow histology findings, the lymphocyte doubling time and the threshold values of blood lymphocyte count with the clinical staging systems to distinguish between indolent disease course and aggressive disease on a prospective basis within a given clinical stage.

Bone Marrow↗
PubMed1984

Chronic lymphocytic leukemia.

This article reviews, for the internist, recent advances in our understanding of the immunology and clinical characteristics of chronic lymphocytic leukemia (CLL). The method of treatment based on clinical staging of CLL and as practiced in the authors' clinic is detailed. It also provides an outline of possible investigation and therapy that may be expected in the coming years.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1984

Circulating monoclonal IgM proteins in B cell chronic lymphocytic leukemia: their identification, characterization and relationship to membrane IgM.

Accumulated evidence indicates that there is a circulating monoclonal Ig protein related to the leukemic cell-associated Ig in the majority of patients with B cell chronic lymphocytic leukemia (CLL) despite the failure to demonstrate such a protein by conventional serum electrophoresis. Methodology has been developed to reveal these hidden monoclonal bands and to show that they are related to the leukemia-associated membrane Ig (mIg). Of nine CLL cases with stainable mIgM and without discernable plasma Ig bands, marked hypogammaglobulinemia was evident in six. In the other three, a significant amount of protein was present in the gamma region. IgM was isolated from the plasma of these patients by affinity chromatography with Sepharose-4B, conjugated with affinity purified anti-human IgM antibodies. One to 3 mg were isolated from 20 to 40 ml of plasma. Agarose electrophoresis revealed a monoclonal Ig band in the isolated IgM in all cases. Eight of these IgM proteins were analyzed by high-pressure liquid chromatography. Five were found to be pentameric IgM. In the remaining three, various amounts of monomeric IgM were detected. Attempts to make anti-idiotypic antibodies to the isolated proteins have been successful. Thus far, a rabbit anti-idiotypic antiserum was obtained in one case and two mouse monoclonal anti-idiotypic antibodies in two additional cases. Immunofluorescence analysis revealed that plasma IgM and mIgM shared similar idiotypic determinants. One other monoclonal antibody was shown to be specific for a V region marker of a minor Ig population. These findings indicate that B leukemic lymphocytes do secrete a small amount of IgM and lend further support to the thesis that the maturation defect in CLL is incomplete. It is also feasible to isolate the secreted IgM and to produce anti-idiotypic antibodies to them. In view of the potential therapeutic effect of anti-idiotypic antibodies, this may offer an alternative and efficient approach to generate a large panel of anti-idiotypic antibodies for clinical trials. The possibility also exists that this approach is applicable to other B cell proliferative disorders such as the non-Hodgkin B cell lymphomas.

Animals↗
PubMed1980

Bone marrow biopsy and clinical staging in chronic lymphocytic leukemia.

We have examined the value of bone marrow biopsy histopathology in chronic lymphocytic leukemia (CLL). Cases involving a pattern of interstitial, nodular, or mixed interstitial plus nodular infiltration of lymphocytes were clinically similar and manifested a more benign course. These patterns correlated with the clinical Stages 0, I, and II. However, cases involving a pattern of diffuse or mixed diffuse plus nodular infiltration of lymphocytes formed a clinical group with a more rapidly progressive course and these patterns correlated with clinical Stages III and IV. Other measurements, e.g., calculation of the percentage of lymphatic tissue in the bone marrow biopsy specimen and of the ratio of the percentage of lymphatic tissue in marrow to the peripheral blood lymphocyte count, were found to be cumbersome to perform and of no additional value to clinical staging in prognosis indication in CLL.

Biopsy↗
PubMed1980

Combination chemotherapy for terminal-phase chronic granulocytic leukemia: cancer and leukemia group B studies.

A 34% response was obtained in 202 evaluable patients in the terminal phase of chronic granulocytic leukemia using combinations of hydroxyurea, 6-mercaptopurine, and corticosteroids. Twelve percent of responses were complete and 22% partial. Overall median survival was 12 wk. A 30 wk median survival for responding patients was statistically superior to the 7-wk survival for nonresponders (p less than 0.001). Response was inversely correlated with toxicity. No responses were obtained in patients sustaining both severe infectious and bleeding complications. No benefit could be demonstrated from the addition of vincristine in induction and daunorubicin for consolidation. Although the response frequency and duration of survival with this combination chemotherapy were generally superior to those previously reported by our group, the terminal phase of chronic granulocytic leukemia still remains a formidable and generally refractory disease.

Daunorubicin↗
PubMed1979

Correlation of total body potassium and leukemic cell mass in patients with chronic lymphocytic leukemia.

Total body leukemic mass in patients with chronic lymphocytic leukemia (CLL) was measured by quantitation of total body potassium (TBK) with a whole-body counter. In addition, the predicted normal total body potassium (Kp) for each patient was calculated from an empirically derived relationship involving height, weight, age, and sex. Both the absolute TBK and the relative excess of total body potassium (TBK/Kp) were related to the stage of disease. Patients in the early stages of CLL were found to have lower TBK and TBK Kp than patients in the late stages of disease. Both of these parameters increased with the successively advanced stages of the disease. The clinically monitored reduction of leukemic cell mass following therapy was accompanied by reductions in TBK and TBK/Kp. Data presented support the notion that TBK/Kp is a useful indicator of the total body leukemic mass. Furthermore, the results of these studies quantitatively validate the proposed clinical staging system for CLL. Quantitation of TBK by a whole-body counter is an accurate and noninvasive procedure and does not require administration of isotopes.

Humans↗
PubMed1977

Comparison of daily versus intermittent chlorambucil and prednisone therapy in the treatment of patients with chronic lymphocytic leukemia.

Ninety-six patients with stage III and stage IV chronic lymphocytic leukemia (CLL) were randomized into one of three treatment schedules. Prednisone was common to all three schedules and was given daily in an initial dosage of 0.8 mg/kg for the first 14 days, with successive halving of the daily dose on days 15 and 29 for a total 6-wk course. Prednisone was then given once a month at 0.8 mg/kg once a day for each of 7 consecutive days. Schedule I was prednisone plus chlorambucil (CLB) given as a once-a-month dose of 0.4-0.8 mg/kg; schedule II was both drugs, but the CLB was given as a daily dose of 0.08 mg/kg; schedule III was prednisone alone. Complete and partial remission (CR + PR) was 47% for schedule I, 38% for schedule II, and 11% for schedule III. Patients who responded (CR + PR) in each of the treatment schedules survived longer than the nonresponders. Complete remission was obtained in both CLB treatment schedules, but not with the prednisone alone regimen. Although overall survival was best in the intermittent CLB arm, there was no significant difference in survival time between the three treatment schedules. Toxicity was minimal in all three regimens. Augmentation of the intermittent monthly CLB, even to 1.5 and 2.0 mg/kg, was tolerated without undue marrow toxicity. About 22% of these patients either had diabetes mellitus at the time of entry on the study or manifested hyperglycemia during the course of treatment and observation.

Anemia↗
PubMed1976

Mediastinal irradiation for chronic lymphocytic leukemia.

Thirty-one patients with chronic lymphocytic leukemia were treated with mediastinal radiation. In none of the patients was complete remission achieved; either partial remission or clinical improvement was achieved in 52 per cent, but the duration of response was short. The response rate was 77 per cent for the patients receiving a total radiation dose greater than 3,000 rads and 45 per cent for those receiving less than 3,000 rads. Severe life-threatening toxicity was noted in 11 patients and seven of these patients died; two patients died with progressive disease. Severe toxicity was manifested by one or more of the following: bone marrow aplasia, pancytopenia, gram-negative sepsis, generalized herpes zoster and severe esophagitis. Neither the total dose of radiation nor the dose per week correlated withe the severity of reaction or death.

Aged↗
PubMed1975

Clinical staging of chronic lymphocytic leukemia.

A method of clinical staging of chronic lymphocytic leukemia (CLL) has been proposed which is based on the concept that CLL is a disease of progressive accumulation of nonfunctioning lymphocytes: stage O, bone marrow and blood lymphocytosis only; stage 1, lymphocytosis with enlarged nodes; stage II, lymphocytosis with enlarged spleen or liver or both; stage III, lymphocytosis with anemia; and stage IV:lymphocytosis with thrombocytopenia. Analysis of 125 patients. in the present series showed the following median survival times (in months) from diagnosis: stage 0, is greater than 150; stage I 101; stage II, 71; stage III, 19; stage IV, 19, The median survival for the entire series was 71 mo. The prognostic significance of the stage remained even after adjustment was made for age and sex. However, both sex and age were shown to be poor predictors of survival after adjustment for stage. The method of staging proved to be a reliable predictor of survival whether used at diagnosis or during the course of the disease. The proposed staging system was an equally accurate indicator for survival when applied to two other previously published studies of large series of patients

Adrenal Cortex Hormones↗
PubMed1975

Survival of chromium-51-labeled autologous and homologous erythrocytes in goats.

Apparent half-survival time of 51-Cr-tagged caprine erythrocytes after autotransfusion was 8 days. The 51Cr-tagged homologous caprine erythrocytes disappeared from circulation very rapidly, thereby indicating that it is not possible to produce sustained polycythemia in goats by hypertransfusing them with homologous erythrocytes without appropriate matching.

Animals↗