Biomedical subjects

Bernard Grosbois

Publications and source records attributed to Bernard Grosbois.

15 recordsLinked to original sources

PubMed2007

Genetic abnormalities and survival in multiple myeloma: the experience of the Intergroupe Francophone du Myélome.

Acquired genomic aberrations have been shown to significantly impact survival in several hematologic malignancies. We analyzed the prognostic value of the most frequent chromosomal changes in a large series of patients with newly diagnosed symptomatic myeloma prospectively enrolled in homogeneous therapeutic trials. All the 1064 patients enrolled in the IFM99 trials conducted by the Intergroupe Francophone du Myélome benefited from an interphase fluorescence in situ hybridization analysis performed on purified bone marrow plasma cells. They were systematically screened for the following genomic aberrations: del(13), t(11;14), t(4;14), hyperdiploidy, MYC translocations, and del(17p). Chromosomal changes were observed in 90% of the patients. The del(13), t(11;14), t(4;14), hyperdiploidy, MYC translocations, and del(17p) were present in 48%, 21%, 14%, 39%, 13%, and 11% of the patients, respectively. After a median follow-up of 41 months, univariate statistical analyses revealed that del(13), t(4;14), nonhyperdiploidy, and del(17p) negatively impacted both the event-free survival and the overall survival, whereas t(11;14) and MYC translocations did not influence the prognosis. Multivariate analyses on 513 patients annotated for all the parameters showed that only t(4;14) and del(17p) retained prognostic value for both the event-free and overall survivals. When compared with the currently used International Staging System, this prognostic model compares favorably. In myeloma, the genomic aberrations t(4;14) and del(17p), together with beta2-microglobulin level, are important independent predictors of survival. These findings have implications for the design of risk-adapted treatment strategies.

Adolescent↗

PubMed2006

Spontaneous megakaryocytic colony formation does not discriminate between essential thrombocythemia and polycythemia vera.

Laboratory detection of spontaneous growth of colony-forming unit-megacaryocytes (CFU-MK), allowing us to distinguish essential thrombocythemia (ET) from reactive thrombocytosis, is therefore useful for the diagnostic of this myeloproliferative disorder. Whether CFU-MK assays allow us to discriminate at least partly between ET and other myeloproliferative disorders such as polycythemia vera (PV) remains, however, to be established. To gain insights about this point, we have performed CFU-MK cultures from bone marrow cells of patients diagnosed with ET (n = 42) or PV (n = 50) using a standardized collagen-based serum-free method. Spontaneous growth of CFU-MK was similarly detected in both 40/42 patients with ET and 47/50 patients with PV. These data suggest clearly that the CFU-MK assay is useful to detect not only ET, but also PV, but fails to discriminate, even partly, between these two myeloproliferative disorders.

Adolescent↗

PubMed2006

Introduction.

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Editorial↗

PubMed2005

Dexamethasone-based regimens versus melphalan-prednisone for elderly multiple myeloma patients ineligible for high-dose therapy.

Dexamethasone alone increases life expectancy in patients with relapsed multiple myeloma (MM); however, no large randomized study has compared dexamethasone and dexamethasone-based regimens with standard melphalan-prednisone in newly diagnosed MM patients ineligible for high-dose therapy. In the Intergroupe Francophone du Myélome (IFM) 95-01 trial, 488 patients aged 65 to 75 years were randomized between 4 regimens of treatment: melphalan-prednisone, dexamethasone alone, melphalan-dexamethasone, and dexamethasone-interferon alpha. Response rates at 6 months (except for complete response) were significantly higher among patients receiving melphalan-dexamethasone, and progression-free survival was significantly better among patients receiving melphalan (P < .001, for both comparisons), but there was no difference in overall survival between the 4 treatment groups. Moreover, the morbidity associated with dexamethasone-based regimens was significantly higher than with melphalan-prednisone, especially for severe pyogenic infections in the melphalan-dexamethasone arm and hemorrhage, severe diabetes, and gastrointestinal and psychiatric complications in the dexamethasone arms. Overall, these results indicated that dexamethasone should not be routinely recommended as first-line treatment in elderly patients with MM. In the context of the IFM 95-01 trial, the standard melphalan-prednisone remained the best treatment choice when efficacy and patient comfort were both considered. These results might be useful in the context of future combinations with innovative drugs.

Aged↗

PubMed2005

[Human iron deficiency].

Iron deficiency is the most widespread nutritional disorder in the world, affecting an estimated 1.2 billion people. Its prevalence is particularly high in developing countries (Africa, Asia, South America), but iron deficiency remains a public health problem in industrialised countries. Three successive stages of iron deficiency can be distinguished: iron store depletion, iron-deficient erythropoesis and iron-deficiency anemia. Investigations of iron deficiency should take into account the clinical background. In groups at risk (infants and children, women of childbearing age, pregnant women), management is limited to nutritional inquiries, gynecological examination, and oral iron supplementation. In men and post-menopausal women, iron deficiency is assumed to result from occult gastrointestinal bleeding, and this may necessitate upper and lower gastrointestinal endoscopy. Benign lesions are more frequently found in the upper digestive tract than in the lower digestive tract. When these investigations are negative and iron supplementation is unsuccessful, video-capsule endoscopy is recommended. Oral iron treatment is based on ferrous salts (200 mg/d). The duration of treatment depends on the severity of iron deficiency, ranging from three months for iron store depletion and iron-deficient erythropeisis to six months for iron-deficiency anemia.

Anemia, Iron-Deficiency↗

PubMed2003

Single versus double autologous stem-cell transplantation for multiple myeloma.

BACKGROUND: We conducted a randomized trial of the treatment of multiple myeloma with high-dose chemotherapy followed by either one or two successive autologous stem-cell transplantations. METHODS: At the time of diagnosis, 399 previously untreated patients under the age of 60 years were randomly assigned to receive a single or double transplant. RESULTS: A complete or a very good partial response was achieved by 42 percent of patients in the single-transplant group and 50 percent of patients in the double-transplant group (P=0.10). The probability of surviving event-free for seven years after the diagnosis was 10 percent in the single-transplant group and 20 percent in the double-transplant group (P=0.03). The estimated overall seven-year survival rate was 21 percent in the single-transplant group and 42 percent in the double-transplant group (P=0.01). Among patients who did not have a very good partial response within three months after one transplantation, the probability of surviving seven years was 11 percent in the single-transplant group and 43 percent in the double-transplant group (P<0.001). Four factors were significantly related to survival: base-line serum levels of beta2-microglobulin (P<0.01) and lactate dehydrogenase (P<0.01), age (P<0.05), and treatment group (P<0.01). CONCLUSIONS: As compared with a single autologous stem-cell transplantation after high-dose chemotherapy, double transplantation improves overall survival among patients with myeloma, especially those who do not have a very good partial response after undergoing one transplantation.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2003

Impact of frontline fludarabine and cyclophosphamide combined treatment on peripheral blood stem cell mobilization in B-cell chronic lymphocytic leukemia.

Ongoing studies in B-cell chronic lymphocytic leukemia are evaluating autologous peripheral blood stem cell (PBSC) transplantation in first remission following fludarabine therapy. However, fludarabine could impair PBSC harvest. In 38 patients after frontline oral fludarabine and cyclophosphamide (FDR-CY) therapy, we prospectively evaluated steady state filgrastim- or lenograstim-primed PBSC mobilization to collect 2.0 x 106/kg or more CD34 cells. The first mobilization, performed a median of 178 days (range, 69-377 days) from the last FDR-CY course, was unsuccessful in 32 patients. This result was significantly associated with a low platelet count before mobilization but not with age, interval from last FDR-CY course, initial stage, remission status, or other blood parameters. Finally, after 1, 2, and 3 mobilizations in 27, 10, and 1 patients, 2.0 x 106/kg or more CD34 cells were collected in only 12. Explorations of the mechanism of poor mobilization and adaptation of PBSC harvest policies after fludarabine treatment are therefore warranted.

Adult↗

PubMed2003

Localized epidural and bone amyloidosis, rare cause of paraplegia in multiple myeloma.

We report two cases of spinal cord compression by AL amyloid deposits in the setting of multiple myeloma. The first patient, a 57 year old man, had a surgical procedure late in his course, when his neurological status worsened despite medical treatment. The second patient, a 61 year old man, had surgical treatment as soon as vertebral body collapse and epiduritis were diagnosed and spinal amyloidosis revealed a non secretory myeloma. Neurological recovery was significant in both cases and neither developed manifestations of systemic amyloidosis 4 years later.

Amyloidosis↗

PubMed2002

Oncogenesis of multiple myeloma: 14q32 and 13q chromosomal abnormalities are not randomly distributed, but correlate with natural history, immunological features, and clinical presentation.

Multiple myeloma (MM) is a plasma-cell malignancy characterized by marked epidemiological, biological, and clinical heterogeneity. The goal of this study was to find a genetic basis for this heterogeneity. Using fluorescence in situ hybridization, we analyzed a prospective cohort of 901 patients with various plasma-cell disorders--monoclonal gammopathies of undetermined significance, smoldering MM, MM, and primary plasma-cell leukemia--for genetic abnormalities involving the 13q14 and 14q32 chromosomal regions; the patients were consecutively enrolled in the Intergroupe Francophone du Myélome clinical trials, We performed statistical analyses comparing these chromosomal abnormalities in terms of immunological (ie, immunoglobulin types and light-chain subtypes) and clinical status and, to some extent, prognostic features. It was found that 14q32 translocations and del(13) are the most frequent chromosomal abnormalities, observed in 75% and 45% of the patients, respectively, and are not randomly distributed, but interconnected. Second, correlations between them allowed us to define 4 major genetic categories of patients: (1) patients lacking any 14q32 abnormality (25%) and generally also lacking del(13); (2) patients presenting either t(4;14) or t(14;16), almost always associated with a del(13) (15% of patients); (3) patients with other 14q32 abnormalities and presenting del(13) (25%); and (4) patients with other 14q32 abnormalities but not presenting del(13) (35%). Third, we show that this genetic stratification is highly correlated with immunological status and clinical presentation and with some major prognostic factors. For the first time, this study gives genetic support to the heterogeneity observed in patients with MM and demonstrates that the 14q32 and 13q chromosomal abnormalities are not randomly distributed. The strong correlations we found might be the basis for a novel genetic classification of MM, as has been previously demonstrated for leukemias and lymphomas. Furthermore, our study supports different models for MM oncogenesis.

Adult↗

PubMed2002

Comparison of 200 mg/m(2) melphalan and 8 Gy total body irradiation plus 140 mg/m(2) melphalan as conditioning regimens for peripheral blood stem cell transplantation in patients with newly diagnosed multiple myeloma: final analysis of the Intergroupe Francophone du Myélome 9502 randomized trial.

High-dose therapy has become a common treatment for myeloma. The objective of this study (Intergroupe Francophone du Myélome [IFM] 9502 trial) was to compare in a prospective and randomized trial the 2 most widely used conditioning regimens before autologous stem cell transplantation in newly diagnosed symptomatic patients younger than 65 years old: 8 Gy total body irradiation plus 140 mg/m(2) melphalan (arm A) versus 200 mg/m(2) melphalan (arm B). A total of 282 evaluable patients were compared--140 in arm A and 142 in arm B. Baseline characteristics and disease response to 4 cycles of the VAD regimen performed before randomization and autologous stem cell transplantation were identical in the 2 treatment arms. In arm B, hematologic recovery was significantly faster for both the duration of neutropenia and thrombocytopenia, transfusion requirements were also significantly lower, and the median duration of hospitalization was significantly shorter. In arm A, the incidence of severe mucositis was significantly increased. The median duration of event-free survival was similar in both arms (21 vs 20.5 months, P =.6), but the 45-month survival was 65.8% in arm B versus 45.5% in arm A (P =.05). This difference might be attributed in part to better salvage regimens after relapse in arm B compared with arm A. We conclude that 200 mg/m(2) melphalan is a less toxic and at least as effective conditioning regimen when compared with 8 Gy total body irradiation with 140 mg/m(2) melphalan. This regimen should be considered as the standard of care before autologous stem cell transplantation in multiple myeloma.

Adult↗

PubMed2002

[Intermittent fever of neoplastic origin].

Cancer and hemopathy account from 4.5% to 14% of causes of intermittent fever (IF). The tumoral etiology is loss frequent in IF than continues fever. The man physiopathologic mechanism is represented by secretion of cytokines from tumour cells. IF may be the presenting symptom of cancer. This case diagnosis is usually made by cautions clinical evaluation and imaging. When cancer is known, IF can be related to infectious diseases or neoplastic evolution.

Cytokines↗

PubMed2002

Current treatment strategies for multiple myeloma.

Until 1990, the melphalan-prednisone regimen was the standard treatment for multiple myeloma (MM). The role of alpha-interferon still remains controversial, both in induction therapy and in maintenance therapy. Over the last 10 years, there has been considerable improvement in the treatment of MM. In patients under 65 years of age, high-dose therapy with autografting has clearly demonstrated an advantage over conventional treatment. Bisphosphonates have proved very useful in reducing skeletal events. More recently, an old drug, thalidomide, has shown surprising efficacy in patients with advanced MM. Future trends include the extension of high-dose therapy to older patients and the use of immunotherapy in induction and/or maintenance therapy.

Journal Article↗

PubMed2002

Thalidomide in patients with advanced multiple myeloma: a study of 83 patients--report of the Intergroupe Francophone du Myélome (IFM).

BACKGROUND: To evaluate treatment by thalidomide and identify predictive factors of survival, event free survival and response among patients with advanced multiple myeloma treated with thalidomide as single agent therapy. PATIENTS AND TREATMENT: Patients with advanced multiple myeloma (n=83) were treated with an oral dose of thalidomide (median 400 mg/day). At start of treatment, all patients had active disease and 58 (69%) had received at least one autologous transplantation. RESULTS: With a median follow-up of 338 days (range, 247-629 days), 52 patients are alive, whereas 31 died between 8 and 150 days after the first administration of thalidomide. The response to thalidomide was considered as major in 11 patients (13%), partial in 29 patients (35%) and minor in 15 patients (18%), giving a total response rate of 66% (54 out of 83 patients). Thirteen patients had stable disease and 15 patients progressed. In multivariable analysis, age greater than 60 years, short interval between diagnosis and onset of thalidomide, requirement for red blood cell transfusion, IgA isotype, platelets' count <80 x 10(9)/l and serum albumin level <30 g/l at the start of thalidomide were associated with poor outcome. These three last factors produced a simplified prognostic model for patients with advanced myeloma and treated with thalidomide. Thus, among the 38 patients without any of these unfavorable risk features, one-year overall survival and event free survival were 87% and 78%. By contrast, the 43 patients with at least one unfavorable feature had one-year overall survival and event free survival of 40% and 32%, respectively (Log-Rank, P=0.0002 for both). Patients who received > or =34.4 g of thalidomide in the first 90 days of treatment had a better outcome than those who received <34.4 g. However, the mean received daily dose of thalidomide in the first 90 days has not been found to influence survival, event free survival or response. Short-term side effects of thalidomide were generally moderate. CONCLUSION: Thalidomide is an effective treatment for patients with advanced myeloma, in particular, who have no poor-risk features. The poor results achieved by the other patients emphasize the need for prospective protocols using thalidomide in combination, especially with dexamethasone. In addition, further studies are needed to determine the optimal thalidomide dose and duration.

Adult↗

PubMed2002

[Clostridium difficile infection in a Department of Internal Medicine. A consecutive series of 45 patients].

OBJECTIVES AND METHODS: A retrospective study of 45 patients with Clostridium difficile infection over a 4-year period in a department of Internal Medicine. RESULTS: Mean age was 79 years; sex-ratio (F/M)=1.5; 38% of the patients had neurological or severe psychiatric disorders; 20% had a neoplastic disease. Ninety-three percent of cases had received one or more antibiotics before onset of diarrhea, prescribed mainly for a pulmonary infection. Amoxicillin clavulanic acid and cephalosporins were the most frequently used treatments, respectively in 48% and 40% of cases. For 25 patients (56%) Clostridium difficile-associated diarrhea was considered as a nosocomial infection, and as community-acquired diarrhea in 20 cases (44%). Treatment included isolation of the patient as soon as bacteriological diagnosis was known and specific therapy was instituted by metronidazole or vancomycin for a mean of 18 days. The addition of Saccharomyces boulardii was used in of cases. The clinical course was rapidly favorable for 80% of patients. Five patients died with complications of severe colitis in 2 cases. Mean hospital stay was 49 days (annual mean of the department=10 days). CONCLUSION: Clostridium difficile diarrhea concerns above all elderly patients with one or more underlying pathologies. Amoxicillin clavulanic acid and third-generation cephalosporins are the most frequently prescribed antibiotics in these cases and have the highest correlation with this infectious complication. This medical problem requires greater knowledge as it causes significant morbidity and increases the risk of prolonged hospital stays.

Aged↗

PubMedDate not supplied

[Monoclonal gammopathies of undetermined significance and their progression over time. Retrospective study of 190 patients].

INTRODUCTION: Monoclonal gammopathies of undetermined significance (MGUS) occur in up to 1% of persons aged 50 years or older. The risk of its progression to multiple myeloma or related disorders is also approximately 1% per year. OBJECTIVES: Our study had two aims: to describe the risk of malignant progression of patients examined in our center for MGUS, and to identify predictors of this malignant progression. METHODS: We retrospectively reviewed the medical records of patients with MGUS seen in our center from 1980 through 1995. Information about progression came either from the medical file or from responses to questionnaires sent to patients' general practitioners. RESULTS: The study included 190 patients. Median follow-up was 84 months (range: 12-240 months). MGUS remained stable for 128 patients (67.37%), whose median follow-up was 96 months. Malignant transformations occurred in 41 patients (21.58%). The median interval from diagnosis of MGUS to diagnosis of a lymphoplasma cell proliferative disorder was 49 months. The cumulative probability of progression was 13.05% at 5 years and 25.14% at 10 years. The initial concentration of serum monoclonal protein was a significant predictor of progression (threshold value: 15 g/L). DISCUSSION: The cumulative probability of progression in our study is higher than that observed elsewhere. Our results may well be biased by the short follow-up period and selective referrals. CONCLUSION: The initial concentration of serum monoclonal protein is a significant predictor of malignant progression of MGUS.

Adult↗