Biomedical subjects

S H Advani

Publications and source records attributed to S H Advani.

At least 37 records · Page 2Linked to original sources

PubMed2001

2-CdA in the treatment of hairy cell leukaemia.

INTRODUCTION: Hairy cell leukaemia (HCL) is a rare lymphoproliferative disorder. Treatment options available are splenectomy, interferon, DCF and 2-CdA. 2-CdA is considered to have curative potential as proved by the other studies. METHODS: We gave 2-CdA in a dose of 0.09/kg/day as a continuous infusion in sixteen patients of hairy cell leukaemia. RESULTS: Three patients developed neutropenia post transfusion. At the end of three months all patients were in remission. Two patients relapsed at the median follow-up of 15 months. CONCLUSION: 2-CdA in HCL can achieve complete remission, prolonged survival and care as well.

2-Chloroadenosine↗

PubMed2000

Actin polymerization in response to different chemoattractants is reduced in granulocytes from chronic myeloid leukemia patients.

Chronic myeloid leukemia (CML), a hematopoietic stem cell disorder, is characterized by the presence of Philadelphia chromosome (Ph1). Earlier studies have shown that various functions, such as chemotaxis, fluid phase pinocytosis, phagocytosis, and degranulation in response to chemotactic peptide formyl-methionyl-leucyl-phenylalanine (fMLP), were defective in polymorphonuclear leukocytes (PMNL) from CML patients. These functions depend on actin microfilaments (MF). Further studies showed that fMLP-induced actin polymerization was lower in CML PMNL. To see if this defect is specific to stimulation by fMLP alone or is a global phenomenon involving other chemoattractant receptors, chemotaxis and actin polymerization were studied in response to fMLP, an analog of fMLP, formyl-methionine-1 aminocyclooctane 1 carboxylic acid-phenyalanine-O-methionine (FACC8), platelet-activating factor (PAF), and leukotriene B4 (LTB4). These compounds bind to different chemoattractant receptors. Chemotaxis and actin polymerization in response to all four chemoattractants were significantly lower in CML PMNL compared with PMNL from normal subjects and were differentially affected for the different chemoattractants. These results suggest a global phenomenon involving all four chemoattractant-stimulated pathways. This lower amount of F-actin may be responsible for the defective chemotaxis seen in these cells.

Actin Cytoskeleton↗

PubMed2000

Circulating levels of TNF alpha and TNF receptor superfamily members in lymphoid neoplasia.

We have correlated the serum levels of TNF alpha and soluble TNF receptor superfamily members with clinico-pathologic parameters in patients of Hodgkin's disease (HD, N = 26) and non-Hodgkin's lymphoma (NHLs, N = 35). HD patients had significantly higher levels of TNF alpha, sTNFRI, and sTNFRII in serum while NHL patients had significantly higher levels of sTNFRI, sTNFRII, sCD27, and sFas as compared to controls. In NHL patients the levels of sCD27 correlated directly and significantly with the high-stage disease, bone marrow involvement, lymph nodal presentation, and serum LDH levels. Similarly in NHL patients, levels of sFas also correlated directly and significantly with the presence of high stage disease. HD patients with B symptoms had significantly higher levels of sTNFRII.

Adolescent↗

PubMed2000

High cytosolic pool of p75 TNF receptors and delayed surface downmodulation by mononuclear cells from non-hodgkin's lymphoma patients.

Analysis of the expression of TNF-Rs on fresh peripheral blood mononuclear cells (PBMNC) by Scatchard analysis showed that Gr I (stages I and II) but not Gr II (stages III and IV) NHL patients have a significantly higher expression of surface TNF-Rs than normal controls. A rapid decrease in the binding of radiolabelled anti-p75 TNF-R Mab which gradually increased after 16 h was seen in normal controls, while NHL patients showed a rapid increase in the binding of the Mab after activation of cells and a decrease in binding was observed only after 24 h. Western blot analysis for normal controls showed a weak presence of the 42 kDa fragment only, while the cytosolic extracts from fresh PBMNCs of NHL patients showed presence of both intact p75 TNF-R, as well as a 42 kDa fragment corresponding to a soluble form of p75 TNF-R. Our results suggest that increased cytosolic pools of TNF-R in NHL patients might contribute to a rapid increase in its surface expression following activation of cells.

Adult↗

PubMed2000

Epstein-Barr virus association in classical Hodgkin's disease provides survival advantage to patients and correlates with higher expression of proliferation markers in Reed-Sternberg cells.

BACKGROUND: Most Epstein-Barr virus (EBV) associated lymphoproliferative disorders have high proliferation indices. However, classical Hodgkin's disease (cHD) is heterogeneous, with respect to proliferation index of the Reed-Sternberg cell (RS cell), and EBV association. Hence, we investigated whether cHD with and without EBV-association differ with respect to the proliferation index of the RS cells. Further we investigated whether this would have a bearing on patients survival. PATIENTS AND METHODS: We investigated 110 cases of cHD for: a) EBV association by immunohistochemical demonstration of EBV-latent membrane protein-1 and EBV encoded nuclear RNA 1 by mRNA in situ hybridisation; b) Proliferating cell nuclear antigen (PCNA) expression in the RS cells. RESULTS: EBV association was noted in 86 of 110 cases (78%). Higher PCNA expression (P = 0.004) and younger age (P = 0.001) correlated independently with EBV association. The 10 year relapse free survival (RFS) of EBV+ and EBV- patients were 60% and 44%, respectively (P = 0.03). The 10 year overall survival (OS) of EBV+ and EBV- patients were 85% and 64%, respectively (P = 0.03). EBV association maintained its significant impact on RFS and OS within Cox proportional hazard model. CONCLUSIONS: Our study suggests that EBV is likely to confer a higher PCNA expression and also contribute towards maintaining the RS cells of cHD in cell cycle. Hence, RS cells in EBV associated cHD would be more responsive to chemotherapy and radiotherapy associated DNA damage. Thus, EBV-association provides survival advantage to cHD patients treated with standard chemotherapy and radiotherapy protocols.

Adolescent↗

PubMed2000

Discrepancies in Epstein-Barr virus association at presentation and relapse of classical Hodgkin's disease: impact on pathogenesis.

BACKGROUND: Though Epstein-Barr virus (EBV) has been linked to classical Hodgkin's disease (cHD), only a proportion of cHD cases show EBV-association. While there has been evidence to suggest a crucial role for EBV in the early phase of cHD evolution, we are unclear whether continued presence of EBV is essential for the maintenance of the neoplasm. We have addressed this issue by investigating the EBV-association in paired samples of cHD obtained at presentation and relapse. MATERIALS AND METHODS: We have analysed lymph node biopsy samples from 23 cases of cHD at presentation and relapse. In situ hybridization with EBER-1 probe and immunostaining with anti latent membrane protein-1 (LMP-1) antibody was performed on the paraffin sections. PCR for EBNA 3C gene was performed for EBV subtype analysis on the DNA extracted from paraffin sections. RESULTS: EBV-association was documented in both the presentation and relapse samples of 14 cases. One case showed loss of EBV-association at relapse. PCR analysable DNA was obtained from both presentation and relapse samples in four of the EBV-associated cases. The EBNA 3C amplimer corresponded to type A strain of EBV in all the samples. CONCLUSION: Loss of EBV-association between presentation and relapse seen in one case implies a hit and run mechanism in EBV-induced lymphomagenesis. Though EBV may be essential early in the evolution of cHD, it may not be required for maintenance of the neoplastic clone. Our study also brings out a speculation that a proportion of EBV-negative cHD could represent loss of EBV in the tumour prior to clinical presentation. Alternatively, an unidentified lymphotropic virus other than EBV might play a pathogenetic role in EBV-negative cHD.

Burkitt Lymphoma↗

PubMed2000

A prospective randomized study of Chop versus Chop plus alpha-2B interferon in patients with intermediate and high grade non-Hodgkin's lymphoma: the International Oncology Study Group NHL1 Study .

UNLABELLED: The addition of a brief alpha interferon regimen to each CHOP induction cycle, plus one year of alpha interferon thrice weekly maintenance therapy, has no early effect on response rates or survival in patients with Intermediate or High grade cell NHL. BACKGROUND: The CHOP (Cyclophosphamide, Adriamycin. Vincristine, Prednisone) regimen is the most widely used first-line therapy for patients with Intermediate or High Grade (IG/HG) non-Hodgkin's lymphoma (NHL). Alpha 2b interferon (INF) enhances response rates and improves survival in low-grade NHL. The International Oncology Study Group (IOSG) conducted a prospective randomized study comparing CHOP alone or combined with INF in patients with IG/HG-NHL. The primary study aim was to compare the objective response rates in these patient cohorts. PATIENTS AND METHODS: Patients with a confirmed diagnosis of measurable NHL of International Working Formulation (IWF) groups D to H histology were randomized to receive CHOP alone or CHOP with 5Mu INF s.c. for 5 days on days 22 to 26 of each 28 day cycle with INF 5 million units (Mu) given three times per week subcutaneously for 52 weeks in those patients who responded to CHOP plus INF. RESULTS: The overall response rates were equivalent in both groups: CHOP alone (214 patients) 81% (complete 55%, partial 26%); CHOP plus INF (221 patients) 80% (complete 54%, partial 26%). At 36 months, the actuarial survival rate was equivalent in both groups. CONCLUSIONS: There is no apparent early advantage in terms of response or survival conferred by adding the study INF regimen to CHOP therapy for patients with IG/HG-NHL.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2000

A prospective randomized study of alpha-2b interferon plus hydroxyurea or cytarabine for patients with early chronic phase chronic myelogenous leukemia: the International Oncology Study Group CML1 study.

A prospective randomized international study of 143 patients showed no apparent early survival advantage conferred by combining cytarabine, rather than hydroxyurea, with INF as first-line CML therapy. Combinations of alpha-interferon (INF) and chemotherapeutic agents are currently first-line therapy for the majority of patients with chronic myeloid leukemia (CML). The International Oncology Study Group conducted a prospective randomized study comparing INF combined with hydroxyurea or cytarabine. The primary study aim was to compare the survival durations in these patient cohorts. Patients with early chronic phase CML were randomized to receive INF 5 million units (Mu) given five times per week subcutaneously plus hydroxyurea or cytarabine as required to achieve a complete hematologic response and to maintain a WBC count between 2x10(9)/L and 10x10(9)/L and a platelet count between 75x10(9)/L and 100x10(9)/L. Therapy continued as tolerated unless progressive or blast phase disease occurred. At 36 months, the actuarial survival rate was equivalent in both groups: HI group (79 patients) survival was 85% (95% CI, 68-100%), as compared to 95% (95% CI, 79-100%) in the CI group (64 patients). In conclusion if seems that there is no apparent early survival advantage conferred by combining cytarabine, rather than hydroxyurea, with INF as first-line CML therapy.

Adolescent↗

PubMed2000

Hydroxyurea induced leg ulcers.

A 34 years non diabetic lady with chronic myeloid leukaemia (CML) was treated with hydroxyurea and interferon. She developed leg ulcers. First time on left toe and three months later on right foot, a rare complication of hydroxyurea. Both were treated with local wound care and antibiotics. First time dose of hydroxyurea was reduced and second time drug was discontinued.

Adult↗

PubMed1999

Acute promyelocytic leukemia: all-trans retinoic acid (ATRA) along with chemotherapy is superior to ATRA alone.

This study was conducted to compare the results of treatment of acute promyelocytic leukemia (APL) with all-trans retinoic acid alone (ATRA) or a combination therapy of ATRA followed by chemotherapy. Forty-three patients treated between February 1992 and February 1996 were included in this study. Eighteen patients were treated with ATRA alone and 25 patients were treated with ATRA followed by chemotherapy. The cytogenetic analysis was done in 41 patients at presentation, following treatment, and at follow-up. A complete response (CR) was achieved in 13 (72%) patients on ATRA and 19 (76%) on ATRA followed by chemotherapy. Eleven of 13 patients with response to ATRA alone relapsed with median survival of eight months (range, 1 to 28). One patient died of hepatitis in CR and one patient is alive 2 years after diagnosis. In the combination therapy arm, 10 patients are in CR with a median follow-up of 22 months (range, 6 to 56 months). After achieving a CR, four patients died due to infections during chemotherapy therapy, and only 5 of 19 patients have relapsed. Major cytogenetic response was seen in 8 of the 10 patients in whom cytogenetic data was available after treatment with ATRA at the time of remission. Similarly, 13 of 15 for whom data was available showed a major cytogenetic response after treatment with ATRA plus chemotherapy. Prior to relapse, 80% of the patients had an increase in the percentage of t(15;17) cells in the marrow. Patients with a complete hematological response but no cytogenetic response relapsed within six months. Ten patients died prior to response evaluation. Two patients who received ATRA died of retinoic acid syndrome, one of pneumonia, and one of intracranial hemorrhage. Of the six patients on ATRA and chemotherapy, four died of retinoic acid syndrome (RAS), one of intracranial hemorrhage, and one of left ventricular failure. Only one patient is alive at 24 months following treatment with ATRA alone. The relapse-free survival is 42% at four years for patients treated with ATRA followed by chemotherapy. This trial is a historical comparison of ATRA alone and ATRA with subsequent combination chemotherapy. Nonetheless, the trial shows a significant improvement in the event free survival of patients receiving chemotherapy as consolidation following ATRA.

Adolescent↗

PubMed1999

Sezary cells with hairy projections.

A case of sezary syndrome where the sezary cells showed cytoplasmic hairy projections is reported. The patient had typical exfoliative erythematous dermatitis, high white cell count, atypical lymphocytes of T-phenotype with folded nuclei and bone marrow involvement. The ultra structure study showed cerebriform nucleus and cytoplasmic projections.

Adult↗

PubMed1999

Altered release of tumor necrosis factor and its soluble receptor in non-Hodgkin's lymphoma patients.

Increased expression and elevated serum levels of tumor necrosis factor-alpha (TNF-alpha) have been shown to be associated with the presence of constitutional B symptoms and poor prognosis in non-Hodgkin's lymphoma (NHL) patients. Soluble TNF receptors (sTNF-R) are suggested to act as biological buffers in inflammatory conditions by binding and inactivating increased circulating TNF. Whereas studies have shown elevated TNF to be correlated with B symptoms, similar studies showing the status of soluble receptor release in these patients have not been conducted. Here, we show that there is increased soluble p75 TNF receptor release from peripheral blood mononuclear cells (PBMNC) in NHL patients in the early stages of the disease but it is severely depressed in patients with advanced disease. Decreased release is associated with presence of B symptoms in these patients. All NHL patients also show increased TNF secretion and a decreased rate of receptor release with time compared with healthy controls. These findings imply that decreased sTNF-R receptor release, in addition to increased TNF secretion, is also important in predisposing the patients to B symptoms. This opens up the possibility of the use of sTNF-Rs as a therapeutic tool to counter increased TNF and alleviate systemic symptoms in these patients and also as a marker for the progression of the disease.

Adult↗

PubMed1999

Expression of Fas and Fas ligand in Hodgkin's disease.

Fas and Fas ligand expression were investigated in twenty two cases of classical Hodgkin's disease (HD) by immunohistochemistry. While Reed-Sternberg (RS) cells in 7/22 (32%) cases expressed Fas ligand, reactive lymphoid cells expressed Fas ligand in only 2 (9%) cases. In 20/22 (91%) cases, the RS cells expressed Fas. A higher proportion of RS cells in the nodular sclerosis subtype expressed Fas as compared to the mixed cellularity subtype. In 18/22 (82%) cases, Fas expression was also noted in the reactive lymphoid cells. In eight cases, the reactive lymphoid cells were also analyzed by flow cytometry and a majority of them were CD4+CD45RO+. Most of these activated T-cells expressed Fas but were negative for Fas Ligand. To investigate the co-expression of Fas and Fas Ligand in the RS cells, six cases were subjected to Fas and Fas ligand immunostaining on consecutive sections. The co-expression was documented in the RS cells in four of six cases. These six cases with expression of both Fas and Fas ligand were investigated for the incidence of apoptosis. There was no statistically significant relationship between expression of Fas on reactive cells, expression of FasL on RS cells and the proportion of apoptotic reactive cells. In all these cases apoptosis was not observed in the RS cells. Thus Fas - FasL interactions may not lead to apoptosis of the RS cells.

Apoptosis↗

PubMed1999

MALT lymphoma of nasal mucosa treated with antibiotics.

Mucosa associated lymphoid tissue (MALT) lymphomas occur in sites other than the gastrointestinal tract and in the early stages respond to treatment with antibiotics. We report a rare case of nasal mucosal MALT lymphoma which responded to treatment with antibiotics and has since then remained in remission.

Adult↗

PubMed1999

Results of allogeneic bone marrow transplant in chronic myeloid leukaemia following conditioning with busulfan and cyclophosphamide.

OBJECTIVE: To study the outcome of oral busulfan and intravenous cyclophosphamide (BuCY 2 regimen) followed by allogeneic bone marrow transplant (BMT) in a cohort of patients with Philadelphia chromosome (Ph+) chronic myeloid leukaemia (CML) in a single centre. METHODS: From 1991 to March 1998, a total of 27 consecutive Ph+ CML patients received busulfan 4 mg/kg/day over 4 days and cyclophosphamide 60 mg/kg/day over 2 days followed by infusion of HLA-identical sibling haematopoietic stem cells. All except one (who received peripheral blood stem cells) were given donor bone marrow cells. Post-transplant graft versus host disease (GVHD) prophylaxis included a short course of methotrexate (on days +1, +3, +6 and +11) and cyclosporine till day +180. RESULTS: With a median follow-up of 30.5 months (1-55+ months), 14 patients (52%) are alive free from relapse. Early mortality was relatively high with 10 patients (37%) dying within first 100 days post-transplant. Acute GVHD developed in 14 patients (52%) inspite of GVHD prophylaxis with methotrexate and cyclosporine; six had grade I/II and eight grade III/IV. Chronic GVHD developed in five of 15 patients who lived beyond 70 days. CONCLUSION: Allogeneic BMT appears to result in eradication of CML and ensure disease free survival in about half of the young patients. However, efforts should be on to minimise early mortality.

Adolescent↗

PubMed1999

Hairy cell leukemia--results with alpha interferon therapy.

Hairy cell leukemia (HCL) is a rare lymphoproliferative disorder. Although now multiple treatment options are being available, the optimal treatment of this disease still remains debatable. Inspite of the advent of newer purine analogues, in India recombinant interferon is the only freely available first line treatment. We report our experience of long term remissions in HCL with interferon alpha 2a. Of a total of 35 cases of HCL we were able to treat 19 cases with interferon. Of 18 evaluable cases an overall response of 88.9% was achieved. With a median follow up of 31 months a disease free survival was 83%. Thus with a dose of 3 million units s.c. daily for 6 months at least, we feel that a reasonably good long term remission can be obtained. The cost of the treatment however, is still a deterrent.

Adult↗

PubMed1998

Translocation (11;14)(q13;q32) and overexpression of cyclin D1 protein in a CD23-positive low-grade B-cell neoplasm.

We describe a case of low-grade B-cell neoplasm with features overlapping between B-chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). The patient presented with a 10-year history of stable CLL without any treatment. The peripheral-blood picture was consistent with atypical mixed CLL (French-American-British criteria), whereas the lymph-node histology was more consistent with MCL. Neoplastic cells were strongly positive for surface immunoglobulin M, kappa, CD5, CD20, CD23, and cyclin D1. Expression of CD11c was weak. Translocation (11;14) and der(10)t(10;?)(p11;?) were the primary cytogenetic changes observed in both peripheral blood (47%) and lymph node (7%). Trisomy 12 was absent. Deletion 6q21 and rearrangements involving 1p/q, consistently associated with progression in lymphomas, also were noted in the peripheral blood but were nonclonal. The present case and similar cases with features overlapping between CLL and MCL most likely represent hybrids. In cases with features of typical CLL, t(11;14) is probably associated with gradual progression and may precede clinical and histologic transformation.

Chromosomes, Human, Pair 11↗

PubMed1998

Cytogenetic studies in patients from India with T-acute lymphoblastic leukemia.

Cytogenetic analysis was performed in 30 patients with T cell acute lymphoblastic leukemia (11 adults, 19 children) at initial presentation and analysis was also repeated in clinical and hematological remission in 15 patients. At initial presentation, chromosomal abnormalities were detected in 27 cases (90%) and hypodiploidy was detected in 19 patients (63.3%), followed by pseudodiploidy in six patients (20%) and hyperdiploidy in two patients (6.6%). Other karyotypic abnormalities detected were deletion 6q (40%), deletion 11 q (16.6%), deletion 7q (10%), abnormalities of chromosome 9 in (13.3%) and translocation t(11;14)(p13;q11) in 6.6% and der(12)t(12;?)(p13;?) in (3.3%). In complete remission, nine out of 15 cases (60%) showed chromosomal aberrations. Original abnormalities were detected in two cases (13.3%) and new abnormalities were detected in seven cases (46.6%).

Adolescent↗