Biomedical subjects

S H Advani

Publications and source records attributed to S H Advani.

At least 19 recordsLinked to original sources

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↗

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↗

PubMed1998

A randomized comparison of the efficacy and toxicity of epirubicin and doxorubicin in the treatment of patients with non-Hodgkin's lymphoma.

BACKGROUND: Combination chemotherapy consisting of methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisolone, and bleomycin (MACOP-B) has been frequently used for the treatment of non-Hodgkin's lymphoma. This randomized study was undertaken to assess the efficacy and toxicity of this regimen when either doxorubicin or epirubicin was used as the anthracycline drug. METHODS: Between April 1989 and December 1993, 211 previously untreated patients with intermediate grade and high grade non-Hodgkin's lymphoma were randomized to receive either doxorubicin (n=106) or epirubicin (n=105) with the MACOP-B regimen. These patients were followed through December 1996. Numerous clinical features predictive of response and survival were analyzed. Cardiac and noncardiac toxicity in the two treatment arms were compared. RESULTS: The median age of the patients was 48 years. Complete remission was experienced by 122 patients (58.3%); 62 patients (58.5%) achieved complete remission in the doxorubicin arm and 60 (58.1%) in the epirubicin arm. Response rates, time to treatment failure, relapse data, and overall survival were comparable between the two arms. Morbidity due to mucositis, vomiting, peripheral neuropathy, and cardiotoxicity were also comparable. The overall mortality was 10%. Mortality due to neutropenic sepsis was considerably higher among patients who received epirubicin (10 patients) than among those who received doxorubicin (5 patients). Cardiac evaluation revealed no difference in toxicity between the two arms. CONCLUSIONS: Epirubicin was as effective as doxorubicin in terms of patients' responses to therapy. There was no difference in cardiotoxicity between the two treatment arms. However, in this study, the mortality due to neutropenic sepsis was significantly higher among patients treated with epirubicin.

Adolescent↗

PubMed1998

Restriction fragment length polymorphism of the L-myc oncogene in non-Hodgkin's lymphoma patients from India.

We examined 89 non-Hodgkin's lymphoma (NHL) patients of Indian origin for EcoRI restriction fragment length polymorphism (RFLP) of the L-myc gene with a view to testing the hypothesis that the presence of the L-myc S-allele predisposes towards NHL. We found no significant difference either in the distribution of the LL, LS and SS genotypes or in the allelic frequencies between the patient group and the control group with the frequencies of L-myc alleles, L (10.0 kb) and S (6.6 kb), being 0.56 and 0.44, respectively, in the patient group and 0.54 and 0.46, respectively, in the control group. However, a higher proportion (70%) of the S-allele was observed in our control group of normal healthy volunteers. Thus, the presence of L-myc S-allele did not indicate increased susceptibility or predisposition to the malignancy.

Adolescent↗

PubMed1998

Hepatitis B vaccination in acute lymphoblastic leukemia.

Active immunization against hepatitis B virus infection was carried out in 162 patients with acute lymphoblastic leukemia attending the Outpatient Department at Tata Memorial Hospital. Recombinant DNA vaccine was given in three doses at 0, 1 and 2 months followed by a booster 1 year after the first dose. Antibodies to hepatitis B surface antigen could be detected in 19.7% of patients following vaccination. Of these only 10.5% had titers in the protective range. Immunosuppression induced by both disease and treatment appears to diminish responsiveness to vaccination. Passive active prophylaxis with both vaccine and immunoglobulin may be a more effective alternative in these patients.

Adolescent↗

PubMed1998

Trisomy 12 in chronic lymphocytic leukemia--geographical variation.

Incidence of trisomy 12 was studied in 60 cases of chronic lymphocytic leukemia (CLL) with chromosome 12 specific alpha-satellite DNA probe by fluorescence in situ hybridization (FISH). Trisomy 12 was observed in 37 (61.8%) patients. Cells with trisomy 12 were detected in a varying proportion, ranging from > 2% to 86%. Patients with trisomy 12 were predominantly observed with total white blood cell (WBC) count > 80 x 10(9) l(-1) (P < 0.001). In addition, the percentage of trisomy 12 positive lymphocytes correlated with the high WBC counts. Trisomy 12 was observed equally in typical and atypical CLL. 90% of our patients were in the intermediate and high risk groups. It was seen that there was significantly higher percentage of trisomy 12 positive lymphocytes ( > 10%) in the high risk groups (P < 0.05). A higher incidence of FMC7 positivity in atypical CLL was seen in our study. However, there was no significant relationship found between trisomy 12 positivity and expression of either FMC7 or CD23 in our cases. It appears that the CLL that we see at our centre is at a different phase of evolution and perhaps biologically different compared to the CLL seen in the West.

Adult↗

PubMed1998

Protein kinase C isoforms in normal and chronic myeloid leukemic neutrophils. Distinct signal for PKC alpha by immunodetection on PVDF membrane, decreased expression of PKC alpha and increased expression of PKC delta in leukemic neutrophils.

Neutrophils from patients with Chronic Myeloid Leukemia (CML) exhibit defects in several functions. They also show altered phosphorylation-dephosphorylation patterns of several proteins on stimulation with phorbol myristate acetate--a direct activator of protein kinase C (PKC). Since PKC mediates several functions of the neutrophil, in this study we investigate the PKC isoform profile and subcellular distribution in normal and CML neutrophils in an attempt to elucidate their role in CML signalling. Our results show the presence of PKC alpha, betaI, betaII and delta in both the cell types. A distinct and clear signal was obtained for PKC alpha, the isoform reported to be absent or present in very low amounts in normal neutrophils. In addition, PKC alpha was present in significantly lower levels in CML neutrophils while the PKC delta isoform was found in significantly higher amounts in the CML cytosol as compared to that in normal cells. PKC alpha, betaI, betaII and delta isoforms could not be detected in the nucleus of unstimulated normal and CML neutrophils. The altered levels of PKC alpha and delta may be one of the causes for the defects in function exhibited by the leukemic cells.

Antibodies↗

PubMed1998

The role of ifosfamide in paediatric cancer.

Ifosfamide is an active drug in the therapy of paediatric tumours such as rhabdomyosarcoma, Ewings' sarcoma, Wilms' tumour, neuroblastoma, germ cell tumours and lymphomas. Myelosuppression is the major toxicity along with haemorrhagic cystitis. The latter is largely prevented by the use of concomitant mesna.

Antineoplastic Agents, Alkylating↗

PubMed1998

All trans retinoic acid with low dose cytosine arabinoside in the treatment of myelodysplastic syndrome.

The demonstration of synergistic interaction between differentiation inducing agents and DNA synthesis inhibitors suggests that these two groups act by two different mechanisms. We prospectively studied the response rate, response duration, survival, and toxicity in 10 patients with myelodysplastic syndrome (MDS) treated with all trans retinoic acid (ATRA) and low dose cytosine arabinoside (ara-C). These patients diagnosed between October 1993 and May 1995 were treated with ATRA (45 mg/M2/day) for 90 days followed by 90 mg/M2 on alternate day till Day 275; together with Ara-C (10 mg/m2) subcutaneously twice daily for 21 days for a total of 6 cycles. These patients were analyzed for response after 3 cycles of LD Ara-C and at the time of completion of therapy. Toxicity was recorded at the end of each cycle of Ara-C. There were 6 male and 4 female patients in the age range of 24 to 76 years. The morphological diagnosis was chronic myelomonocytic leukemia in 2, refractory anemia with excess blasts in 4 and refractory anemia with excess blasts in transformation in 4. Only 1 patient achieved a complete remission and 1 patient achieved a partial response. Four patients had progressive disease on treatment. One patient died of neutropenic sepsis and 1 of resistant thrombocytopenia and intracranial hemorrhage while on treatment. One patient refused further treatment after a minor clinical response and in 1 patient treatment was stopped due to toxicity. This data in a pilot study with a limited number of patient suggests that ATRA in combination with Ara-C has little effect in MDS.

Aged↗

PubMed1997

A study of p53 protein, proliferating cell nuclear antigen, and p21 in Hodgkin's disease at presentation and relapse.

About one fourth of patients with Hodgkin's disease relapse after therapy. The mechanisms that lead to resistance to treatment in these patients are poorly understood. The authors describe the differential protein expression of p53, proliferating cell nuclear antigen (PCNA), and p21 at initial presentation and relapse, and discuss their role in disease progression and resistance to therapy. Thirty-four patients with Hodgkin's disease who had relapsed after standard chemotherapy and radiotherapy regimens were assessed for the expression of p53 protein, PCNA, and p21 protein (waf/cip 1). In 14 of these cases, sequential biopsies performed both at presentation and at relapse were available for the study. Seventy-five percent of the cases were positive for the p53 protein. Tumors at relapse had higher p53 and PCNA scores than those at initial presentation. In the paired samples, a significant increase was noted in the number of p53 and PCNA-positive cells and in the intensity of staining with p53 antibody. Six of seven paired samples tested for p21 showed an increased p21 expression at relapse. These results suggest that, at relapse, Reed-Sternberg (RS) cells and their variants positive for p53, PCNA, and p21 are increased in number and individually have an increased expression of p53, PCNA, and p21 proteins. These findings suggest that therapy failure and relapse may, at least in part, be associated with altered p53, p21, and PCNA pathways. HUM PATHOL 28:549-555. This work was carried out during an exchange fellowship program at the National Cancer Institute, Bethesda. There are no restrictions on its use

Adolescent↗

PubMed1997

Chronic myeloid leukemic granulocytes exhibit reduced and altered binding to P-selectin: modification in the CD15 antigens and sialylation.

Granulocytes from patients with chronic myeloid leukemia (CML) egress from the bone marrow before they are functionally mature and exhibit delayed emigration to sites of infection. To understand these defects, we have compared the binding of normal and CML granulocytes to the 293 cell line transfected with cDNA for P-selectin. The CML granulocytes show significantly reduced binding to P-selectin relative to normal cells. The binding of normal granulocytes to P-selectin was significantly reduced when the cells were treated with anti CD15, polyclonal anti-P-selectin, monoclonal anti-P-selectin (G1) antibodies or neuraminidase. On average, only 8% of the CML granulocyte population bound to P-selectin. The antibodies and neuraminidase were ineffective in inhibiting the binding of this population of leukemic cells. These data show that the morphologically mature CML granulocytes consist of a heterogeneous population of cells, some of which do not bind to P-selectin and others which adhere to the molecule via modified sugars.

Antibodies, Monoclonal↗

PubMed1997

Heterogeneity in the expression of Fc gammaRIII in morphologically mature granulocytes from patients with chronic myeloid leukemia.

Morphologically mature granulocytes from patients with chronic myeloid leukemia exhibit a defect in receptor mediated endocytosis of FITC-conjugated heat-aggregated IgG. In our earlier studies, we have shown that transcripts for Fc gammaRII and Fc gammaRIII are lowered in CML granulocytes, while no such trend was seen for CD11b, CD18 and actin, the other molecules involved in this process. We have also shown by flow cytometry that the number of granulocytes expressing the Fc receptors on their surface is lowered in CML patients. In this report, we show that the lowered steady state level of the mRNA for the Fc receptors is due to their faster degradation and not due to any defect in transcription. A study of the expression of mRNA for Fc gammaRIII in morphologically mature CML granulocytes by in situ hybridization showed that there is heterogeneity in the expression of this receptor, with some cells positive for the message and some not. These results suggest that the Fc gammaRIII transcript reaches a stable RNA pool in only some of the granulocytes, whereas in the rest of the cells, it is probably degraded after it is transcribed and is therefore not detected. The Fc gammaRIII is probably one of the first antigens to be lost from the leukemic granulocyte surface during the transition of the disease from the chronic phase to the accelerated phase and finally to the blast crisis.

Antigens, Neoplasm↗

PubMed1997

Pulmonary microsporidial infection in a patient with CML undergoing allogeneic marrow transplant.

Very few cases of human microsporidial infection have been reported. The advent of AIDS has changed this. There is increasing recognition that microsporidia are important opportunistic pathogens. However, the number of cases reported in the non-HIV population is small. We report here a case of microsporidial infection in a female patient with chronic myeloid leukemia undergoing allogeneic bone marrow transplantation. There was also an associated fungal infection. The diagnosis could be reached only after postmortem and was confirmed by electron micrography. We suggest that transplant patients are another group of patients who are susceptible to this group of opportunistic pathogens.

Adult↗

PubMed1997

Gonadal function following ABVD therapy for Hodgkin's disease.

To assess the effect of combination chemotherapy with doxorubicin, bleomycin, viablastine, and decarbazine (ABVD) on gonadal function in patients treated for Hodgkin's disease, we assessed 38 male patients with Hodgkin's disease who were > 15 years of age and in complete remission for the development of secondary sexual characteristics, sexual habits, and fatherhood after treatment. Semen analysis and serum hormone level estimation of follicle-stimulating hormone (FSH), leutinising hormone (LH), and testosterone (T) were done in all cases. Twenty-six patients received ABVD therapy and 12 received a combination of ABVD with COPP or MOPP (cyclophosphamide or nitrogen mustard, vincristine, procarbazine, and prednisone). Radiation of the pelvic region was done in one case. Median time between completion of therapy and assessment of gonadal function was 34 months (range, 12-68 months). Secondary sexual characteristics developed normally in all patients. Azoospermia was seen in one patient from the ABVD group and 10 patients from the COPP/ABVD group (p < 0.001). Serum FSH levels were significantly higher in the COPP/ABVD group than in the ABVD group (23.5 versus 4.7 mlu/ml; p < 0.001) The levels were in the normal range in 23 patients from the ABVD group, as compared to four in the COPP/ABVD group (88.5% versus 33.3%; p < 0.001). Three patients treated with ABVD fathered children post-therapy. We conclude that ABVD is associated with relatively better preservation of gonadal function.

Adolescent↗

PubMed1997

Serum tumor necrosis factor for monitoring response of hepatic veno-occlusive disease to pentoxiphyllin--a case report.

Hepatic veno-occlusive disease (VOD) is the second most common cause of death after autologous bone marrow transplantation (ABMT). A patient with multiple myeloma undergoing ABMT developed classic features of hepatic VOD. He responded to treatment with pentoxiphyllin. Serum tumor necrosis factor (TNF) levels showed remarkable correlation with the severity of VOD and response to therapy.

Adult↗

PubMed1997

Production & evaluation of a monoclonal antibody against human myeloperoxidase.

We describe the production of a mouse monoclonal antibody (H2E1) against human myeloperoxidase antigen. After production and characterisation, this antibody was compared with commercially available monoclonal antibodies, cytochemical myeloperoxidase and previously produced polyclonal antibody. Reaction with various cell lines proved that this monoclonal antibody was specific for myeloid lineage. This monoclonal showed positivity in 81.8 per cent of acute myeloid leukaemias whereas the polyclonal antibody was 100 per cent positive. We found that the polyclonal antibody was more sensitive as compared to the monoclonal. This is probably due to the lack of recognition of individual epitopes on the antigen. We recommend the use of antibodies which have different epitope recognition as most specific for myeloperoxidase.

Animals↗