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X Mariette

Publications and source records attributed to X Mariette.

At least 55 records · Page 3Linked to original sources
PubMed1999

Lymphomas in patients with Sjögren's syndrome: review of the literature and physiopathologic hypothesis.

The occurrence of non Hodgkin's lymphoma (NHL) is the most serious complication of Sjögren's syndrome (SS). Taking the opportunity to study 16 patients with lymphoma and an underlying SS, we performed a review of literature concerning SS and lymphoma and made an hypothesis on the physiopathology of lymphoproliferation in patients with SS. Lymphomas occurring in patients with SS are in most cases low grade marginal zone lymphomas (MZL). They arise frequently in mucosal extranodal sites, not only in the salivary glands but also the stomach and the lung. These lymphomas are not associated with viruses including hepatitis C virus (HCV), Epstein-Barr virus, human herpes virus 8 or human T lymphotropic virus-I, known to be present in other types of lymphomas. Some of the translocations or mutations of oncogenes or anti-oncogenes described in other lymphomas are also detected in SS-associated lymphomas. Lymphomas complicating SS share a number of characteristics with lymphomas complicating HCV infection. We make the assumption that, in both diseases, the first event of lymphomagenesis is the chronic stimulation, on the site of the disease, of polyclonal B-cells secreting rheumatoid factor (RF). Then, these RF B-cells may become monoclonal and disseminate in other organs. The monoclonal secreted RF complexed with polyclonal IgG may cryoprecipitate. The following step would be a chromosomal abnormality (e.g. trisomy 3) which would confer to these cells a low grade B-cell lymphoma compartment. A last event (e.g. mutation of p53) could transform this low grade B-cell lymphoma into a high grade large B-cell lymphoma. If this hypothesis was correct, most of B-cell lymphomas associated with SS should have a surface immunoglobulin with RF activity and should grow through an auto-antigen driven process.

Autoantigens↗
PubMed1999

Anti-p53 antibodies are rarely detected in serum of patients with rheumatoid arthritis and Sjögren's syndrome.

OBJECTIVE: To detect evidence of abnormalities of the p53 protein in autoimmune diseases. Mutation of the p53 protein may inhibit apoptosis and thereby lead to cancer and possibly play a role in the pathogenesis of autoimmune diseases. METHODS: Serum antibodies to p53 are detected in 30 to 50% of patients with cancer who have p53 mutations. Using an ELISA, we determined the prevalence of anti-p53 antibodies in the serum of 106 patients with rheumatoid arthritis (RA), 72 patients with primary Sjögren's syndrome (SS), and 14 patients with lymphoma complicating SS. The presence of anti-p53 antibodies was also measured in the synovial fluid of 16 patients with RA. Positive sera by ELISA were confirmed by immunoprecipitation. RESULTS: Serum anti-p53 antibodies were detected in 2 of 106 patients with RA. The synovial fluid of one of these 2 patients was also studied and was positive. Anti-p53 antibodies were not detected in the other synovial fluids. Serum anti-p53 antibodies were not detected in 72 patients with primary SS alone, but were present in 2 of 14 patients with lymphoma complicating SS. CONCLUSION: Our results suggest that if p53 mutations have any role in the pathogenesis of some autoimmune diseases, they are rarely associated with the presence of anti-p53 antibodies in patients with RA. In patients with SS, the presence of serum anti-p53 antibodies might be an indirect sign of the development of a lymphoma.

Arthritis, Rheumatoid↗
PubMed1998

High-dose therapy and autologous peripheral blood stem cell transplantation in multiple myeloma: up-front or rescue treatment? Results of a multicenter sequential randomized clinical trial.

Results to date indicate that high-dose therapy (HDT) with autologous stem cell support improves survival of patients with symptomatic multiple myeloma (MM). We performed a multicenter, sequential, randomized trial designed to assess the optimal timing of HDT and autotransplantation. Among 202 enrolled patients who were up to 56 years old, 185 were randomly assigned to receive HDT and peripheral blood stem cell (PBSC) autotransplantation (early HDT group, n = 91) or a conventional-dose chemotherapy (CCT) regimen (late HDT group, n = 94). In the late HDT group, HDT and transplantation were performed as rescue treament, in case of primary resistance to CCT or at relapse in responders. PBSC were collected before randomization, after mobilization by chemotherapy, and, in the two groups, HDT was preceded by three or four treatments with vincristine, doxorubicin, and methylprednisolone. Data were analyzed on an intent-to-treat basis using a sequential design. Within a median follow-up of 58 months, estimated median overall survival (OS) was 64.6 months in the early HDT group and 64 months in the late group. Survival curves were not different (P = .92, log-rank test). Median event-free survival (EFS) was 39 months in the early HDT group whereas median time between randomization and CCT failure was 13 months in the late group. Average time without symptoms, treatment, and treatment toxicity (TWiSTT) were 27.8 months (95% confidence interval [CI]; range, 23.8 to 31.8) and 22.3 months (range, 16.0 to 28.6) in the two groups, respectively. HDT with PBSC transplantation obtained a median OS exceeding 5 years in young patients with symptomatic MM, whether performed early, as first-line therapy, or late, as rescue treatment. Early HDT may be preferred because it is associated with a shorter period of chemotherapy.

Adult↗
PubMed1998

Surgical endoscopic techniques in the diagnosis and follow-up of patients with lymphoma.

BACKGROUND: In patients with lymphoma, tissue for histology can be obtained through image-guided techniques or by surgery. The aim of this study was to assess the efficacy of surgical endoscopic techniques in obtaining adequate tissue specimens. METHODS: Ninety-two patients with suspected or confirmed lymphoma were referred for a surgical biopsy of a deeply located intrathoracic or intra-abdominal mass or lymph node. The 86 patients who had surgery using a surgical endoscopic technique were included in this study. There were 54 men and 32 women, of mean age 34 (range 15-78) years. Most were selected directly for surgery while five previously had a failed computed tomography-guided biopsy. A total of 89 procedures were performed in 86 patients: laparoscopy (15 patients), thoracoscopy (61) and mediastinoscopy (13). RESULTS: No patient died. One intraoperative complication occurred during thoracoscopy (1 per cent). Two postoperative complications were noted (2 per cent). Three patients required conversion to open surgery (3 per cent). Adequate tissue for histology was obtained by surgical endoscopic procedures in 87 per cent. Twelve of 13 mediastinoscopies were successful. After thoracoscopy, the success rate was 92 per cent but only nine of 15 laparoscopies were considered successful. CONCLUSION: In patients with lymphoma, surgical endoscopic techniques have a high diagnostic yield and a low morbidity rate. Barring exceptional circumstances these should be favoured rather than conventional open surgery.

Adolescent↗
PubMed1998

Granulocytic sarcoma of the jejunum: a rare cause of small bowel obstruction.

We report the case of a 40-yr-old man presenting with symptoms of small bowel obstruction. Small bowel x-rays revealed a stricture of the mid-jejunum. Push enteroscopy found a polypoid mass at 1 meter of the ligament of Treitz. Histopathological examination of the biopsy and surgical specimens showed a diffuse infiltrate of the mucosa made of medium to large cells, which were stained on immunohistochemistry by the leucocyte marker CD45 and the histiocyte/monocyte marker CD68 but were negative for the B and T cell markers. Cytological examination of the ascitic fluid revealed many myelobasts with cytoplasmic Auer rods and positive myeloperoxidase staining. There was no evidence of blood or bone marrow involvement suggestive of acute leukemia or myeloproliferative disorders. These findings were consistent with the diagnosis of preleukemic granulocytic sarcoma (or chloroma). Chemotherapy led to complete remission, but 21 months later the patient developed an acute myeloid leukemia. He died from aspergillus pneumonitis, 10 months after bone marrow allograft. Preleukemic granulocytic sarcoma of the small bowel is a rare condition and its diagnosis is usually not easy, requiring histochemical or immunohistochemical studies. Most cases have progressed to acute myeloid leukemia.

Adult↗
PubMed1998

Activity of fludarabine in previously treated Waldenström's macroglobulinemia: a report of 71 cases. Groupe Coopératif Macroglobulinémie.

PURPOSE: There is no consensus on the treatment of patients with Waldenström's macroglobulinemia (WM) who develop primary or secondary resistance to frontline therapies. We report our experience on the activity and toxicity of fludarabine in 71 patients with WM resistant to prior chemotherapy regimens. PATIENTS AND METHODS: From January 1991 to June 1995, 71 patients were included in this retrospective study. The median age, median time from diagnosis to treatment, median immunoglobulin M (IgM) level, and median number of previous treatments were 68 years (range, 42 to 81), 5.9 years (range, 0.6 to 20), 35 g/L (range, 5 to 126), and two (range, one to four), respectively. RESULTS: Seventy-one patients received a median of six courses of fludarabine. Twenty-one (30%) responded with a partial response and 50 (70%) were considered as treatment failures. Forty-six patients died: 10 in the responder group and 36 in the failure group. Twenty-five patients were alive with a median follow-up time of 34 months. The overall median survival time of all treated patients was 23 months. The time to treatment failure was 32 months. The only factor that favorably influenced the response to fludarabine was a longer interval between the first treatment and the start of fludarabine. Pretreatment factors associated with shorter survival in the entire population were hemoglobin level less than 95 g/L (P = .02) and platelet count less than 75 x 10(9)/L (P = .02). CONCLUSION: The responses rate in this population with a poor prognosis is close to that reported in shorter series. Patients with WM who are resistant to alkylating agents should be identified early, so that salvage therapy with nucleoside analogs can be started without delay.

Adult↗
PubMed1998

Lymphoproliferative disorders in rheumatoid arthritis patients on low-dose methotrexate.

Methotrexate is the most widely used second-line treatment in rheumatoid arthritis because of its excellent efficacy and safety profile. However, since 1991, about 100 cases of lymphoproliferative disorders have been reported in rheumatoid arthritis patients under methotrexate therapy. Four characteristics similar to those in lymphomas associated with immunodeficiency were identified during a review of the 48 cases for which detailed information is available. (1) Most cases were non-Hodgkin's B-cell lymphomas of the large cell or diffuse mixed type. (2) Extranodal involvement (55% of cases) was unusually common. (3) Evidence of Epstein-Barr infection was found in 46% of tested patients. (4) Of the 14 patients treated by methotrexate withdrawal alone, eight achieved a full remission, with follow-ups ranging from one to five years. These characteristics suggest a role for two factors: (1) the abnormalities in cell-mediated immunity seen in rheumatoid arthritis may promote latent Epstein-Barr virus infection, which may in turn lead to proliferation of malignant lymphoid cells; (2) the immunomodulatory effects of methotrexate may promote the development not only of opportunistic infections but also of Epstein-Barr virus-related lymphoproliferative disorders. There is no firm evidence to date that methotrexate has a direct oncogenic effect and no excess in malignant diseases has been reported with this drug. In conclusion, the rate of occurrence of lymphoproliferative disorders induced by low-dose methotrexate therapy remains controversial, although the characteristics of the malignancies and the possibility of a complete remission after methotrexate withdrawal militate against a chance association. Epidemiologic and other studies are needed to clarify this issue.

Adolescent↗
PubMed1997

Structural analysis of human antibodies to proteinase 3 from patients with Wegener granulomatosis.

We determined the structure of five IgM autoAbs to proteinase-3 (PR3). These Abs are highly specific for Wegener's granulomatosis (WG) and may be involved in the pathogenesis of vasculitis in WG. Five clonal lymphoblastoid cell lines secreting Abs to PR3 were derived from four patients' B cells. From 3 to 5% of supernatants from wells contained detectable anti-PR3 Abs, indicating that anti-neutrophil cytoplasmic Ab specificity represents a sizable part of the IgM B cell repertoire in patients with WG. Mu heavy chains of WG1, WG4-1, and WG4-2 clones belonged to the VH3 subgroup. WG4-1 and WG4-2 heavy chains were identical, indicating an oligoclonal expansion of autoreactive B cells in this patient. WG4-1 (and WG4-2) used the VH3-23 V(H) gene, the product of which was shown to directly bind PR3. Heavy chains of WG2 and WG3 derived from VH4-59 and VH1-2 genes, respectively. Comparison with germline sequences showed that three of the five V(H) genes from clonal lines were somatically mutated with a R:S ratio in complementarity-determining regions of 3:0, 5:1, and 5:1, respectively. Three kappa light chains derived from the Vkappa4 gene, and one derived from a Vkappa1 gene. In these four Vkappa genes, there were overall R:S ratios of mutation of 8:1 and 0:7 in complementarity-determining regions and framework regions, respectively. These data suggest that the production of these autoantibodies, which are increasingly important in the diagnosis and management of WG, are influenced by an Ag-driven process.

Amino Acid Sequence↗
PubMed1997

Lymphomas in patients with Sjogren's syndrome are marginal zone B-cell neoplasms, arise in diverse extranodal and nodal sites, and are not associated with viruses.

The occurrence of non-Hodgkin's lymphoma (NHL) is the most serious complication of Sjogren's syndrome (SS). We performed a study of 16 NHLs occurring in patients with an underlying SS. These lymphomas arose not only in salivary glands (7 cases) but also in other mucosal extranodal sites (the stomach [4 cases], the lung [3 cases], the skin [3 cases], the buccal mucosa [1 case], the thymus [1 case]) and in nodal sites (8 cases). Low-grade marginal zone lymphomas (MZL) were diagnosed in 12 of the 16 patients, 9 of mucosa-associated lymphoid tissues (MALT) type in mucosal sites and 3 exclusively nodal. The 4 other patients presented with a high-grade B-cell lymphoma that was probably a histological transformation of an underlying low-grade MZL at least in 3 of the cases involving skin, stomach, and parotid, respectively. A t(14;18) translocation was detected in 1 of 8 lymphomas tested. We detected serum anti-p53 antibodies in 2 of the 14 studied patients. p53 protein was detected in 1 of 11 lymphomas tested. LMP protein and Eber RNAs of Epstein-Barr virus (EBV) were not detected in the 16 NHL biopsies. Using polymerase chain reaction, EBV was never detected except in 1 of 4 parotid lymphomas. No human T-lymphotropic virus 1 or human herpes virus 8 DNAs were detected in NHL biopsies. None of the patients had hepatitis C virus infection found using serological methods. Chemotherapy was usually efficient. In conclusion, lymphomas occurring in patients with an underlying SS are in most cases MZL. These lymphomas are not associated with viruses known to be present in other types of lymphomas. Some of the translocations or mutations of oncogenes or antioncogenes described in other lymphomas are detected in SS-associated lymphomas.

Adolescent↗
PubMed1997

Prevalence of hepatitis G virus RNA in French blood donors and recipients.

BACKGROUND: Recently, cases of chronic hepatitis were linked to the presence of genomic sequences of a newly described RNA virus termed hepatitis G virus (HGV) and belonging to the Flaviviridae family. STUDY DESIGN AND METHODS: The presence of HGV RNA was searched for by polymerase chain reaction in a population of blood donors and in patients who had received multiple blood component transfusions and/or intravenous immunoglobulin (IVIG) infusions. RESULTS: Twenty-one (4.2%) of 500 donors were positive for HGV RNA as were 21 (10.7%) of 196 nonimmunosuppressed patients who had received multiple transfusions of packed red cells, 4 (8.7%) of 46 common variable immune deficiency (CVID) patients who had received only IVIG, and 22 (24.7%) of 89 bone marrow transplant (BMT) patients who had received IVIG and cellular components. The proportion of HGV-positive individuals was significantly higher in the immunosuppressed recipients (CVID and BMT patients) than in the nonimmunosuppressed patients who were multiply transfused with packed red cells (p < 0.03). The proportion of HGV-positive individuals was significantly higher in the BMT patients who had received IVIG and cellular components than in the CVID patients who had received IVIG only (p < 0.03). Eight (17.0%) of the 47 HGV-positive recipients and 48 (16.9%) of the 284 HGV-negative recipients had a serum alanine aminotransferase level higher than the upper limit of normal (nonsignificant difference). The medical history of HGV-positive donors failed to reveal a particular at-risk event. The large majority of HGV-infected patients had a normal serum alanine aminotransferase level, and the proportion of patients with elevated alanine aminotransferase was the same in HGV-positive and in HGV-negative recipients. CONCLUSION: The pathological significance of HGV infection remains unelucidated, and the classification of HGV as a new hepatitis virus was perhaps premature.

Adult↗
PubMed1997

A randomised clinical trial comparing interferon-alpha and intravenous immunoglobulin in polyneuropathy associated with monoclonal IgM. The IgM-associated Polyneuropathy Study Group.

OBJECTIVES: The polyneuropathy associated with a monoclonal IgM directed to the myelin associated glycoprotein (MAG) is a specific entity with a putative causal link between the IgM and the neuropathy. The small benefit offered by alkylating agents or plasma exchanges in these patients justifies the search for alternative treatments. METHODS: A 12 month multicentre, prospective, randomised, open clinical trial was carried out comparing intravenous immunoglobulin (IVIg; 2g/kg and then 1 g/kg every three weeks) and recombinant interferon-alpha (IFN-alpha; 3 MU/m2 subcutaneously three times weekly). The main end point was a clinical neuropathy disability score (CNDS) after six months of treatment. Twenty patients were enrolled; 10 were assigned to IVIg and 10 to IFN-alpha. RESULTS: At six months, one out of 10 patients treated with IVIg had a CNDS improvement of more than 20% whereas eight out of 10 patients treated with IFN-alpha had such an improvement (P=0.005). The mean CNDS worsened by 2.3 (SD 7.6) (8%) in the IVIg group whereas it improved by 7.5 (SD 11.1) (31%) in the IFN-alpha group (P=0.02). This improvement persisted after 12 months and was mainly related to an improvement of the sensory component (P=0.02) whereas the motor component was unchanged (P=0.39). Electrophysiological data did not show improvement of motor nerve conduction velocities whereas sensory nerve conduction velocities improved in the upper limbs. A decrease in the level of the monoclonal IgM was seen in two patients treated with IFN-alpha. At the end of the treatment, antibody activity to MAG was still detected in the serum of all patients. CONCLUSION: IVIg, as used in this study, did not improve patients with polyneuropathy and monoclonal IgM. By contrast, although its mechanism of action remains to be fully elucidated, IFN-alpha was effective in eight out of 10 patients at six months.

Adult↗
PubMed1996

Absence of cytomegalovirus and Epstein-Barr virus expression in labial salivary glands of patients with chronic graft-versus-host disease.

We investigated in 15 consecutive patients a possible correlation between expression of CMV or EBV in labial salivary gland (LSG) biopsies performed 100 days after allogeneic BMT and subsequent development of chronic GVHD. Three techniques were performed for the detection of each virus: immunohistochemistry, in situ hybridization and PCR. Eleven patients developed chronic GVHD. Histologic examination detected a moderate lymphoid infiltrate (grade 1 according to Sale's score) in LSG biopsy in only one patient. CMV genes or proteins could not be detected in any patients. Likewise, EBV genome or proteins were not detected by in situ hybridization and immunohistochemistry. However, in three of the 15 patients, EBV DNA was detected by PCR in LSG biopsies. Only one of these three patients developed chronic GVHD. Therefore, at the present time, the presence of a lymphoid infiltrate on lip biopsies performed at day 100 post-BMT does not appear to be sensitive enough for the diagnosis or the prediction of the subsequent development of chronic GVHD. Moreover, the absence of EBV and CMV expression in a day-100 LSG biopsy does not preclude the development of chronic GVHD.

Adolescent↗
PubMed1996

[Treatment of peripheral neuropathies associated with IgM anti-myelin monoclonal gammopathy].

Effective therapy of peripheral neuropathies associated with a serum monoclonal IgM remains difficult. Chemotherapy with Chlorambucil yielded a moderate improvement in only a third of the patients. No additional benefit was given with plasma exchanges. However they can be used in case of rapid worsening or of motor of the disease. Intravenous immunoglobulins were not effective in a recent prospective controled study. However, in this study a-interferon yielded improvement in more than half of the patients. These results have to be confirmed and mechanism of action of a-interferon needs to be elucidated.

Humans↗
PubMed1996

Tumoral joint involvement in multiple myeloma and Waldenström's macroglobulinemia--report of 4 cases.

We describe 4 patients, 2 with multiple myeloma and 2 with Waldenström's macroglobulinemia, who developed arthritis due to invasion of articular and periarticular structures by malignant cells. Articular manifestations in lymphoplasmacytic disorders are most often related to metabolic or septic complications, sometimes to immunoglobulin deposits, but can also result from tumoral joint involvement.

Adult↗
PubMed1995

Evolution of bone densitometry in patients with myeloma treated with conventional or intensive therapy.

BACKGROUND: Demineralization is a common hallmark of multiple myeloma (MM) that can be evaluated by dual-energy X-ray absorptiometry (DEXA). The evolution of lumbar and whole body bone density were investigated by DEXA in patients with MM treated by conventional or intensive therapy supported by autologous blood stem cell transplantation. METHODS: Sixty six patients younger than 66 years with MM were randomly assigned to either conventional (30 patients, Group A) or intensive therapy supported by autologous blood stem cell transplantation (36 patients, Group B). For all patients, lumbar bone mineral density (BMD) was measured by DEXA at diagnosis and 13.2 +/- 4.2 months after the initiation of treatment. Whole body examinations were performed in 45 patients; in addition to whole body BMD, independent BMD values were recorded for various skeletal sites. RESULTS: At diagnosis, mean lumbar Z score (lumbar mean BMD value) was low (-1.24 +/- 1.45) without any significant difference between the 2 groups. Under treatment, lumbar BMD increased 0.7% in Group A and 4.6% in Group B (P = 0.02). This difference was mainly related to nonresponders in group A who featured a lumbar BMD change of -3.9%, whereas patients in remission in both groups displayed a 4.1% increase (P < 0.001). There was a correlation between the variation of lumbar BMD and the decrease of the serum or urinary monoclonal component (r = 0.34, P = 0.006). After intensive therapy, increase of lumbar BMD was higher in men than in women (7.2% vs. 1%, P = 0.005) perhaps because of variations in hormonal status in women. Unexpectedly, whole body BMD decreased in responders (-3%) because of a decrease in appendicular BMD outweighing the increase in axial BMD. This suggests a redistribution from cortical to cancellous bone in patients with MM responsive to chemotherapy. CONCLUSION: Bone densitometry is a marker of treatment response that may be particularly useful in nonsecretory and light chain MM. Moreover, it provides new information on bone remodeling in patients treated for MM, which may have therapeutic consequences.

Absorptiometry, Photon↗