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Biomedical subjects

M Hebbar

Publications and source records attributed to M Hebbar.

At least 55 records · Page 3Linked to original sources
PubMed1996

Plasma c-erbB2 concentrations in relation to chemotherapy in breast cancer patients.

Amplification and overexpression of the C-ERBB2 oncogene have been associated with a poor prognosis and a lower response to chemotherapy in human breast cancer. In this study, plasma c-erbB2 concentrations were determined using an enzyme immunoassay in patients with breast cancer. The links between c-erbB2 concentration and tumoral response to chemotherapy were established. The patients with a c-erbB2 concentration higher than the cut-off value (27 U/ml) were considered as c-erbB2+. Ten of the 33 metastatic breast cancers were c-erbB2+. No statistically significant difference in response to chemotherapy was noted between c-erbB2+ and c-erbB2- patients (4/10 objective responses versus 10/23). Variations in c-erbB2 concentrations during treatment were not related to response to treatment.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Prognostic factors in myelodysplastic syndromes: critical analysis of the impact of age and gender and failure to identify a very-low-risk group using standard mortality ratio techniques.

We studied the prognostic value of age and gender by survival, and by standard mortality ratio (SMR) analyses, in 203 untreated patients with myelodysplastic syndromes (MDS); 57 refractory anaemia (RA), 23 refractory anaemia with ringed sideroblasts, 41 refractory anaemia with excess blasts (RAEB), 3 RAEB in transformation (RAEB-T) and 79 chronic myelomonocytic leukaemia (CMML), aged 23-89 years (median 69, M/F 0.5), who were all karyotyped. Median survival was 36 months. Adverse prognostic factors were: high bone-marrow blast percentage, complex karyotype, low platelet count, age > 60 years, low or high WBC count, haemoglobin < 10 g/dl, male gender. However, the standard mortality ratio (i.e. mortality compared to that of an age- and sex-adjusted population) was not different between male and female patients. Patients < 60 had a higher SMR than older patients. Therefore the prognostic values of age and gender for survival in MDS patients may reflect, at least in part, a characteristic of the population. Furthermore, even in low-risk groups defined by scoring system we were unable to define a subgroup of patients with a mortality similar to that of the normal population, especially in MDS patients aged < 60.

Adult↗
PubMed1996

Low incidence of specific anti-platelet antibodies detected by the MAIPA assay in the serum of thrombocytopenic MDS patients and lack of correlation between platelet autoantibodies, platelet lifespan and response to danazol therapy.

We prospectively studied the mechanism of thrombocytopenia in 30 patients with myelodysplastic syndrome (MDS), who had a platelet count <or= 70 x 10(9)/l, and marrows blasts <or= 10% by analysis of platelet lifespan, platelet-bound IgG antibodies by platelet radioactive antiglobulin test (PRAT), and circulating and platelet-bound autoantibodies specifically directed against platelet glycoproteins by indirect and direct MAIPA test. PRAT analysis was positive in 21/30 patients (70%), but antiplatelet antibodies were found in only eight by the MAIPA test. Platelet lifespan was shortened in five cases, only one of whom had a positive MAIPA test. Patients were treated by danazol (600 mg/d), and 9/26 evaluable patients (35%) responded, including three of the five patients with shortened platelet lifespan. No correlation between platelet lifespan, results of PRAT and MAIPA tests, and response to danazol was found. In conclusion, specific antiplatelet autoantibodies, reduced platelet lifespan, and efficacy of androgen therapy on platelets were seen in 20%, 17% and 35% of MDS with thrombocytopenia, respectively, but no correlation between these findings was found in this study.

Adolescent↗
PubMed1995

E-selectin expression in salivary endothelial cells and sera from patients with systemic sclerosis. Role of resident mast cell-derived tumor necrosis factor alpha.

OBJECTIVE: To assess endothelial cell activation in patients with systemic sclerosis (SSc). METHODS: Concomitant study of salivary gland biopsy tissues and sera for expression of E-selectin and its potent activator tumor necrosis factor alpha (TNF alpha), using immunostaining and enzyme-linked immunosorbent essay. RESULTS: E-selectin was overexpressed in SSc patients, but not in controls. TNF alpha was detected in mast cells. CONCLUSION: Mast cell-derived TNF alpha may contribute to endothelial cell activation in SSc.

Adolescent↗
PubMed1995

[Immunotherapy of malignant melanoma. New prospects].

Malignant melanoma is an immunogenic tumor which can induce host humoral and cellular responses, and is a good model for development of anti-cancer immunotherapy. During the last decade systemically-administrated interferon and interleukin-2 have been used. Advances in immunology and molecular biology could allow a more specific and active immunotherapy. Perspectives include chemo-immunotherapy, monoclonal antibodies alone or in combination with cytotoxic agents, adoptive immunotherapy with tumor-infiltrating lymphocytes (TIL), gene therapy designed to increase tumor immunogenicity, and active immunotherapy with vaccines.

Animals↗
PubMed1995

[Systemic diseases in myelodysplastic syndromes].

Myelodysplastic syndromes (MDS) are characterized by quantitative and functional involvement of myeloid lineages. Yet, systemic manifestations, suggestive of a lymphocytic involvement, have been described in MDS. We review here biological and clinical data concerning the associations between MDS and immunological disorders. Biological auto-immune markers are in fact rare in MDS, and especially encountered in the chronic myelomonocytic leukemia subgroup. Only a few systemic diseases seem to be frequently associated with MDS: seronegative arthritis, cutaneous vasculitis, and relapsing polychondritis. These diseases are probably not entirely auto-immune, and the signification of their association with an MDS remains unclear. About 30% of relapsing polychondritis are associated with MDS. Conversely, 0.6% of MDS are associated with a relapsing polychondritis. These associations are mainly encountered in men suffering from a refractory anemia (with or without excess of blasts). The main cytogenetic abnormalities are monosomy 7, presence of a ring chromosome, and monosomy 16.

Arthritis↗
PubMed1995

Participation of cryoglobulinaemia in the severe peripheral neuropathies of primary Sjögren's syndrome.

A peripheral neuropathy is encountered in 10 to 50% of patients with primary Sjögren's syndrome (pSS). The pathogenesis of this complication remains unknown, but severe cases of peripheral neuropathies seem to result from a vasculitis. Since about 20% of pSS are associated with a cryoglobulinaemia, we initiated a retrospective study to assess the participation of cryoglobulinaemia in the severe peripheral neuropathies (SPN) of pSS. We found 6 cases of SPN (presence of pain and/or muscle weakness) in a group of 115 pSS (5%): 3 polyneuropathies and 3 mononeuritis multiplex. In all cases, the involvement was sensoromotor and axonal. Four patients had a biopsy-documented cutaneous vasculitis, and 2 of them had also a muscular lymphocytic vasculitis. A cryoglobulinaemia was detected in sera of 5 patients. Although the research was negative in the remaining patient, the presence of an IgM monoclonal gammapathy and of an hypo-complementaemia suggested also the presence of a cryoglobulinaemia. Complement was activated in the 6 cases. Treatment was aggressive: oral corticosteroid (6 cases), methylprednisolone pulses (4 cases), chloraminophen (1 case), plasma exchanges (2 cases), intravenous immunoglobulins (1 case). A stabilization or a partial regression of the neuropathies were observed in 1 case and 5 cases, respectively. This was associated with a reduction of cryoglobulin level and complement activation in 5 cases and 6 cases, respectively. This study suggests that SPN of pSS result from a cryoglobulin-mediated vasculitis.

Adult↗
PubMed1995

Association of myelodysplastic syndrome and relapsing polychondritis: further evidence.

We report five patients with both a myelodysplastic syndrome (MDS) and relapsing polychondritis (RP), that represented 0.6% of all MDS and 28% of all RP diagnosed over a period of 14 years. Ten other cases had previously been reported (four in detail), supporting a non-fortuitous association between the two disorders, already suggested for MDS and some other immunological disorders.

Adult↗
PubMed1995

[Insufficient efficacy of the use of a single 8 mg tablet of ondansetron in the prevention of nausea and vomiting induced by FEC chemotherapy].

This study was performed in a group of 89 patients treated for breast carcinoma with a FEC regimen (5-fluorouracil, epirubicin, cyclophosphamide). The aim was to evaluate the antiemetic efficacy of one 8 mg tablet ondansetron (OND), and in case of failure, to measure the recovering level by the administration of 8 mg i.v. OND. One tablet of OND was given before the first course. A complete or major control of emetic episodes (EE) (0-2 EE) over the 24 first hours was obtained in 55 patients (62%). A complete or major control of nausea (absent or mild) was obtained in 46 patients (52%). A success, defined as a complete or major control for EE and nausea during the first 5 days, was obtained in 36 patients (40%). These 36 patients were treated again with 8 mg oral OND at the second course, with a success level of 61% (22/36). Among the 53 patients unresponsive to the oral OND, 38 were treated by 8 mg i.v. OND at the second course. A complete or major control for EE and for nausea over the first 24 hours was obtained respectively in 11 patients (29%), and 11 patients (29%). No success was obtained. The 15 remaining patients, who had a very bad tolerance at the first course were excluded from the study and treated by OND-methylprednisolon, with only one success obtained. This study shows that the exclusive use of one 8 tablet OND is not sufficient in prevention of emesis induced by a FEC regimen, and that failures are only partially recovered by the i.v. route.

Administration, Oral↗
PubMed1995

Randomized trial comparing conventional intravenous bolus FEC and FEC with high-dose infusional 5-fluorouracil as first-line treatment of advanced breast cancer.

FEC (5-FU 500 mg/m2, epirubicin 50 mg/m2, and cyclophosphamide 500 mg/m2) administered as a conventional bolus schedule is widely used in treatment of advanced breast cancer. 5-FU is thought to be more efficient when administered at high doses as a continuous infusion. The aim of this study was to compare the response rate, time to treatment failure, and overall survival obtained with standard FEC regimen (group A) and FEC with high-dose infusional 5-FU (750 mg/m2 per day/days 1 to 5) (group B). One hundred and seventy-eight patients entered this study, 89 in each arm; 10 were noneligible. Both groups were comparable for age, performance status, menopausal status, hormonal receptor status and prior treatment of the initial tumor, duration of relapse free interval, and type and number of disease sites. One hundred and forth patients were evaluable for efficacy. The response rate was 33.3% in group A (1.4% complete response-CR), and 39.4% in group B (9.8% CR) (ns). In an intent to treat basis (n = 168) the response rates were 26.8% and 34.1%, respectively, in groups A and B (ns). The response rate in liver metastasis was significantly higher in group B (57.1%) than in group A (20.0%) (P = 0.03). The time to treatment failure and overall survival were not different between the two groups. One hundred and fifty-three patients were evaluable for toxicity. 10.7% of the patients in group A and 16.0% in group B stopped treatment due to toxicity. Stomatitis was more frequently observed in group B than in group A (46.7% versus 2.6%, respectively, p < 10(-9)). The rates of other side effects were similar in the two groups. In conclusion, the two regimens gave similar overall response rates, time to treatment failure and survival, but infusional 5-FU yielded a better response rate in the liver metastasis.

Adult↗
PubMed1993

De novo myelodysplastic syndrome (MDS) with deletion of the long arm of chromosome 20: a subtype of MDS with distinct hematological and prognostic features?

We report on 8 cases of de novo myelodysplastic syndromes (MDS) with deletion of the long arm of chromosome 20 (del 20q), who represented about 2% (8/392) of our cases of de novo MDS with cytogenetic analysis seen during a period of 9 yr. Median age was 69 yr, and there were 7 males and 1 female. Anemia was absent or very mild (Hb > 11 g/dl) in 5 patients. Only 1 patient had neutrophils < 0.5 x 10(9)/l, and none had platelets < 50 x 10(9)/l. Four patients had refractory anemia (RA), 2 had refractory anemia with ringed sideroblasts (RARS), and 2 had refractory anemia with excess of blasts (RAEB). Del 20q was isolated in 5 patients, and associated with other chromosomal rearrangement(s) in 3 patients. Only 1 patient progressed to ANLL and 2 showed an increase in bone marrow blasts during evolution. The 5 other patients had stable disease after 18-77 months. By comparison with de novo MDS patients with other cytogenetic findings, patients with del 20q had a tendency towards lower incidence of anemia and excess of marrow blasts, lower incidence of progression to AML and more prolonged survival, although differences were not significant. Only patients with isolated del 5q had a more prolonged survival than patients with del 20q.

Aged↗
PubMed1993

Long-term survivors in myelodysplastic syndromes: a report on 63 cases and comparison with short and intermediate survivors.

Sixty-three of 373 patients (17%) with de novo myelodysplastic syndrome (MDS) survived more than 5 yr (long survivors). At diagnosis, they usually had no or only moderate cytopenias; 63% of them had marrow blasts < 5%; only 1 patient had circulating blasts; 60% had refractory anaemia (RA) or refractory anaemia with ringed sideroblasts (RARS); 19% of the 43 patients who were karyotyped had an abnormal clone, and only 2 patients had complex cytogenetic findings. Only 4 of the 63 patients progressed to another FAB type within 5 yr of diagnosis, from RA to refractory anaemia with excess of blasts (RAEB) or chronic myelomonocytic leukaemia (CMML). After 5 yr, 9 patients showed progression (including progression to AML in 5 patients). The other patients remained stable (43 cases) or died from cytopenias or unrelated disorders (11 cases). Except for 3 patients who achieved prolonged complete remission with intensive chemotherapy, and possibly 3 patients who responded to low dose Ara C, prolonged survival seemed to result mainly from the low natural course of the disease. Although, as expected, significant differences for age, cytopenias, circulating and bone marrow blasts, and karyotype were seen between short (< 2 yr) and long (> 5 yr) very few significant differences were seen between intermediate and long survivors. These 2 subgroups only differed by significantly lower age and higher haemoglobin level in long survivors. Multivariate scoring systems (Bournemouth, Sanz's and Lille scores) proved of relatively limited value in differentiating them.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Cytogenetic analysis has strong independent prognostic value in de novo myelodysplastic syndromes and can be incorporated in a new scoring system: a report on 408 cases.

Although the prognostic value of cytogenetic analysis has previously been demonstrated in myelodysplastic syndromes (MDS), karyotype had not been included in previously published scoring systems, such as Bournemouth and Sanz's scores. We studied karyotype at diagnosis in 408 cases of de novo MDS (after excluding therapy-related MDS). Karyotypes were classified in 10 groups: normal; isolated del 5q; del 5q and other rearrangements; isolated +8; isolated -7 or del 7q; del 20q; isolated -Y; miscellaneous single rearrangements; -7 or del 7q and other rearrangements; miscellaneous complex rearrangements. Karyotypes were considered complex when at least three chromosomes were rearranged. Complex karyotypes included all patients with del 5q and other rearrangements, -7 or del 7q and other rearrangements, and miscellaneous complex rearrangements (i.e. three of the 10 groups). Median actuarial survival of the 408 patients was 28 months, and 90 patients (22%) progressed to acute myeloid leukemia (AML). For survival, bone marrow (BM) blasts, circulating blasts, white blood cell (WBC), neutrophil count, platelet count, hemoglobin, age, sex, FAB classification, and Bournemouth and Sanz's scores had strong prognostic value. Cytogenetics also had strong prognostic value. An unfavorable cytogenetic group (patients with complex karyotypes) was identified. On the other hand, although patients with isolated del 20q and del 5q had a somewhat better prognosis than other patients with non-complex cytogenetic findings, they could not be statistically individualized as a favorable group, possibly owing to their relatively limited number. By multivariate regression analysis, a three-variable new scoring system could be designed based on karyotype (1 point for complex karyotype; 0 for other groups), platelets (0 for > 75 x 10(9)/l; 1 for < 75 x 10(9)/l), and BM blasts (0 for < 5%, 1 for 5-10%, 2 for > 10%). The total score (addition of points for the three variables) was able to separate patients in three groups with low (score 0) intermediate (score 1 or 2), and high risk (score 3 or 4) which included 34%, 47%, and 19% of the patients, and had a median survival of 55, 24, and 6 months, respectively (chi 2 = 110, p < 10(-4)). This new score (Lille score) was able to subdivide risk groups according to Bournemouth and Sanz's scores into further subgroups of different prognoses. For progression to AML, BM blasts, circulating blasts, WBC count, hemoglobin, FAB type, and karyotype had prognostic value by univariate analysis.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1992

The role of intensive chemotherapy in myelodysplastic syndromes.

We review results of intensive chemotherapy (IC) obtained in myelodysplastic syndromes (MDS). Overall, the complete remission (CR) rates and median CR duration obtained with IC are low in MDS, especially when compared to results obtained in de novo AML treated with the same chemotherapy regimens; very few MDS patients achieve prolonged remissions. Failure to achieve CR, in MDS, results both from a high incidence of resistant disease and toxic deaths, the latter being due to longer periods of aplasia than in de novo AML. However some subgroups of MDS seem to obtain higher CR rates and more prolonged remissions. These include patients younger than 45 to 50 years, those with a large excess of marrow blasts or Auer rods at diagnosis, and patients with a normal karyotype or at least without involvement of chromosomes 5 and/or 7. Results of IC clearly have to be improved in MDS. Higher CR rates may possibly be obtained by intensifying induction regimens, but this will probably require the addition of growth factors, in order to reduce the already very long periods of aplasia seen with IC in MDS. For consolidation therapy, new approaches, and especially autologous bone marrow transplantation, will have to be investigated.

Adult↗