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S Advani

Publications and source records attributed to S Advani.

65 records · Page 4Linked to original sources

Characterisation of blast cells during blastic phase of chronic myeloid leukaemia by immunophenotyping--experience in 60 patients.

The blast cell population of 60 patients with chronic myeloid leukaemia in blast crisis (CML-BC) were analyzed with a panel of monoclonal antibodies to determine the cell surface antigen phenotypes. In addition, cytochemical stains periodic acid Schiff (PAS), myeloperoxidase (MP), Sudan black B (SBB) and terminal deoxynucleotidyl transferase (TdT) were also utilized for subtyping. Nineteen cases (31.6%) expressed lymphoid phenotypes characteristic of common ALL cells and one case with extramedullary lymph node crisis expressed T-cell surface phenotypes. Thirty cases (50%) expressed solely myelomonocytic surface antigens with significant TdT activity in three. Cytochemical stains contributed to recognize only 57% of these myeloid blasts. Seven cases (11.7%) were with a mixture of heterogenous group of cells expressing phenotypic characteristics for various haemopoietic cells of different lineage--five of them from the cells of non-lymphoid series (myelomono-erythromegakaryocytic series) and the other two with cells from both lymphoid and myeloid series. Additionally, in two cases (3.3%), the precursor cells reacted only with the erythroid monoclonals. Finally, in one case, the blast cells remained unclassified due to nonreactivity with any of the monoclonals used but expressed significant TdT positivity. The response to uniform vincristine and prednisolone (V + P) therapy has shown that lymphoid blast crisis cases were highly responsive in contrast to the cases with non-lymphoid blast crisis (complete remission rate 86 vs 21.4%). The results confirm the evidence of multilineage blast crisis involving either single or mixed haemopoietic differentiation pathway and the utility of having phenotypic characterisation for designing protocols for chemotherapy in the CML patients at the time of blast crisis.

Adolescent↗

Evidence for the presence in sera from chronic myelogenous leukemia patients of an activity that enhances the number of normal bone marrow-derived granulocyte/monocyte committed stem cell colonies.

In serum from chronic myelogenous leukemia (CML) patients an activity has been demonstrated, which recruits more CFU-GM (cells committed to granulocyte-macrophage lineage) from normal human bone marrow into clonal proliferation as shown by standard agar colony forming assay, in the presence of supramaximal levels of colony stimulating activity. All sera from CML patients at diagnosis (before therapy) were tested and found to be significantly (P less than 0.001) positive for the recruitment activity. This observation led us to believe that younger or more pluripotent CFU-GM which were hitherto non-responsive to colony stimulating activity become responsive in the presence of CML sera. We investigated whether more pluripotent stem cells (CFUs) are stimulated to proliferate in the chronic phase of CML than at diagnosis (before therapy). An activity was detected which recruits more spleen colony forming cells (CFUs) from normal Swiss mouse bone marrow into the cell cycle as shown by a significant increase (P less than 0.001) in the thymidine suicide index. However both these activities were either lowered or undetectable in normal (blood groups AB) serum. These results indicate that CML sera may contain enhanced levels of early growth factors which stimulate proliferation of pluripotent stem cells resulting in an increased CFU-GM pool in CML. It is suggested that this activity may be responsible for the myeloid hyperplasia associated with CML in the chronic phase.

Bone Marrow Cells↗

Natural and antibody-dependent cellular cytotoxicity in chronic myeloid leukemia patients in remission.

Non-adherent peripheral blood mononuclear cells (NA-PBMNC) from 67 chronic myeloid leukemia (CML) patients in the first and two subsequent remissions, and 23 normal healthy donors were tested for NK and ADCC activities in short term chromium release assays using K562 and antibody-coated chicken RBCs as respective targets. CML patients in remission exhibited significantly reduced NK cytotoxicity (16. 1-19.7%) compared to normal healthy donors (47.4%). Of the patients tested, 55% exhibited NK levels below the mean percent cytotoxicity--2SD (12.5%) of normal donors (low responders), while 45% exhibited NK cytotoxicity above the 12.5% level (normal responders). On the other hand, CML patients in remission showed ADCC activity comparable to that of normal healthy donors (53.3%) irrespective of whether they belonged to normal NK responder group (55.5-65.0% ADCC) or low NK responder group (39.4-48.3% ADCC). The low or normal NK responder status of CML patients was not found to be related to either progression on the disease, or the type of drug used to bring about remission, or to the period in remission at the time of testing. In-vitro treatment of effector lymphocytes with recombinant human IFN alpha resulted in augmented of NK activity in both low and normal NK responder patients. The IFN-augmented NK activity in low responder patients however remained below the normal levels.

Antibody-Dependent Cell Cytotoxicity↗

Pediatric Hodgkin's disease in India.

Twenty-one percent of all Hodgkin's disease in India was seen in the pediatric age groups at the Tata Memorial Hospital (Bombay, India). From 1975 to 1982, 151 cases of children were reviewed. The youngest presentation was at 3 years in three patients, with a marked male: female ratio of 5.5:1. Twenty-six patients were previously treated before referral while the remaining 125 cases were investigated and treated according to the prevalent protocols in 1975 to 1978 and 1979 to 1982. Clinical staging revealed 54% of patients in stages I and II with symptoms in 20%, and 46% of patients in stages III and IV with symptoms in 67%. Staging laparotomy was performed in 27 patients, with a total changes of staging in 17 children (63%). The mixed cell types (46%) and lymphocytic predominant types (31%) were the most common histologic presentations. Nine percent nodular sclerosis and 9% lymphocytic-depleted varieties were also observed. Five percent of all cases were not classifiable. Minimum adequate treatment was completed in 87 cases. Comparisons were made between the treatments administered to 40 patients during the initial period 1975 to 1978 when individualized treatment was administered, and the later 47 patients during the 1979 to 1982 period, when chemotherapy was the mainstay of treatment with involved field radiation.

Actuarial Analysis↗

Circulating immune complexes in chronic myeloid leukemia patients at various stages of the disease.

Circulating immune complexes (CICs) in sera from patients suffering from chronic myeloid leukemia (CML) at initial diagnosis, in 'remission', at relapse and in blastic crisis have been quantitated using fluid [125I]Clq binding assay in terms of per cent binding activity and microgram/ml aggregated human globulin (AHG) equivalents. The Clq binding activity (Clq-BA) has been compared within the groups of CML patients in different phases of the disease as well as with sera obtained from normal healthy donors. The results showed that the mean Clq-BA was significantly increased in CML patients at initial diagnosis (25.74 +/- 3.48, p less than 0.001), in relapse (53.36 +/- 6.9, p less than 0.001) and in blastic crisis (60.5 +/- 8.7, p less than 0.001) when compared to control sera. Sera of 'remission' patients showed significant decrease in Clq-BA when compared to sera collected in active phases of the disease, however, the values were still significantly higher (12.87 +/- 1.58, p less than 0.02) than those of normal healthy donors. When the levels of CICs as assessed by Clq-BA were compared with the WBC/blast counts of CML patients in chronic as well as blastic phase, it was noted that the variations in numbers of circulating leukemic cells do not correlate with the CIC levels. The significance of assessment of CIC levels in monitoring the disease in CML patients is discussed.

Acute Disease↗

Report of an International Network of Cancer Treatment and Research workshop on non-Hodgkin's lymphoma in developing countries.

The International Network of Cancer Treatment and Research (INCTR) recently organized a workshop on non-Hodgkin lymphomas (NHLs) in selected developing countries with the purpose of examining existing information relating to the pathology and management of these neoplasms, and identifying potential areas for research. This report provides a summary of the information presented and is focused primarily on the pathology of NHLs in children and adults. In most countries, the WHO classification of lymphomas was used and most participating centers included immunohistochemistry using a wide array of lymphoid antibodies as part of routine diagnosis. Some of the series had been reviewed by an external panel of experts. B-cell lymphomas accounted for 82-88% of all NHLs. The proportions of chronic lymphatic leukemia (4-6%), mantle cell lymphoma (MCL, 3-5%), and plasmacytoma (2-4%) were similar in the series presented. However, there was a significant variation in the proportion of follicular lymphoma (FL), which accounted for 15% and 11% in India and Kuwait, but less than 5% in Pakistan and Egypt. All of these frequencies are significantly lower than those reported in Western series. Diffuse large B-cell lymphoma accounted for about 35% of cases in India but for more 50% in other countries, but this difference was not accounted for by an increased incidence in a single lymphoma subtype in India, but rather an apparent paucity of several subtypes (such as mantle cell and marginal zone lymphomas (MZL)) in other series. There were relatively high frequencies of Burkitt lymphoma in Egypt (7%) and precursor T-cell lymphoblastic lymphoma in India (6-7%). Peripheral T-cell lymphomas (PTCLs) (not otherwise specified and angioimmunoblastic subtypes) accounted for 3-5% of NHLs, and extranodal lymphoma of T/NK cell type was rare (<1%). These differences in the relative proportions of NHL subtypes among developing countries and between developing countries and the rest of the world presumably arise from differences in environmental and genetic factors that influence lymphomagenesis and strongly suggest that more research in developing countries would provide valuable insights into the pathogenesis of lymphoid neoplasms.

Adult↗

Inhibition of DNA synthesis by lonidamine and hyperthermia in human chronic myeloid leukemia cells.

Lonidamine (LNA) is antitumor agent that lacks the characteristic properties of antiproliferative drugs and has narrow spectrum of antitumour effects. It is also a hyperthermia sensitizer. Hyperthermia affects on various cellular organelles, and the malignant cells are known to be more sensitive to hyperthermia. The present study examines the in vitro effects of LNA (0.01 and 0.02 mM) and hyperthermia (42 degrees C for 1 and 2 hrs) alone and in combination, on 11 human chronic myeloid leukemia cell samples. The inhibition in incorporation of 3H-thymidine was statistically significant (P less than 0.001) in human CML cells when exposed to the combination of LNA (0.01 and 0.02 mM) with hyperthermia (1 and 2 hrs) compared to the single treatment either at the same concentration of LNA at 37 degrees C or hyperthermia alone. Cytotoxicity was evaluated as the inhibition of the incorporation of 3H-thymidine in the cellular nucleic acid. The drug effects were estimated from the changes in rates of incorporation of precursor into DNA and compared with untreated control samples. Cancer cells were incubated in vitro in the presence of radioactive 3H-thymidine and drug.

Antineoplastic Agents↗