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C Thieblemont

Publications and source records attributed to C Thieblemont.

At least 19 recordsLinked to original sources
PubMed2006

A clinicopathological study of nodal marginal zone B-cell lymphoma. A report on 21 cases.

AIMS: To report the clinicopathological findings of 21 cases of primary nodal marginal zone B-cell lymphoma (NMZL). NMZL is a recently characterized lymphoma and few series have been published. METHODS AND RESULTS: The clinical data were characteristic of a disseminated disease at presentation: presence of peripheral and abdominal lymph nodes, bone marrow involvement (62%), disease stage III and IV (76%), elevated lactate dehydrogenase (LDH) (48%). Other features included peripheral blood involvement (23%), anaemia (24%), thrombocytopenia (10%) and presence of serum M component (33%), while the previously reported association with hepatitis C virus and cryoglobulinaemia was not found. Relapses were frequent but the majority of patients receiving chemotherapy had a good initial response. Morphological features were heterogeneous and there were some differences compared with other marginal zone B-cell lymphomas (MZL). Pure monocytoid B-cell lymphomas were rare (10%) but a minor component of monocytoid B cell was observed more frequently (23%). Plasmacytoid or plasmacytic differentiation was a very common feature (61%). Large cells and a high mitotic count were also frequent (57%). CONCLUSION: NMZL can be distinguished from splenic MZL and extranodal MZL by its aggressive morphology and disseminated disease at presentation.

Adult↗
PubMed2005

Identification and characterization of two genes (MIP-1beta, VE-CADHERIN) implicated in acute rejection in human heart transplantation: use of murine models in tandem with cDNA arrays.

BACKGROUND: Genes and mechanisms of action involved in human acute rejection after allogeneic heart transplantation remain to be elucidated. The use of a murine allograft model in tandem with cDNA arrays and quantitative real-time polymerase chain reaction (Q-PCR) can greatly help in identifying key genes implicated in human heart acute rejection. METHODS AND RESULTS: Hearts from Balb/c mice were either not transplanted or transplanted heterotopically in the abdomen of Balb/c (isografts) and C57BL/6 (allografts) mice. Histological analysis showed acute rejection only in allografts. Total RNA was extracted from isografts (n=3), allografts (n=4), and not transplanted hearts (n=4); reverse transcribed; and labeled with P32. Each probe was hybridized to cDNA macroarrays. Eight genes were overexpressed and 7 genes were underexpressed in allografts compared with isografts. Macrophage inflammatory protein-1beta (MIP-1beta), an overexpressed gene, and VE-cadherin, an underexpressed gene, were validated by immunohistochemistry and Q-PCR in the murine models. Genes of interest, validated in the 3 murine groups, were then investigated in human heart tissues. Immunohistochemistry and Q-PCR performed on endomyocardial biopsies after heart transplantation showing no rejection (n=10) or grade IB (n=10) or IIIA (n=10) rejection, according to International Society of Heart and Lung Transplantation criteria, confirmed the results obtained from the murine model. CONCLUSIONS: We have demonstrated that the upregulation of MIP-1beta and downregulation of VE-cadherin may strongly participate in human acute heart rejection.

Animals↗
PubMed2005

Cytogenetic analysis delineates a spectrum of chromosomal changes that can distinguish non-MALT marginal zone B-cell lymphomas among mature B-cell entities: a description of 103 cases.

The purpose of this study was to document the frequency and distribution of karyotypic changes present at diagnosis in 103 non-MALT marginal zone cell lymphoma (MZL) patients. This cytogenetic analysis of a large cohort extends previous observations and allows the identification of new cytogenetic features. Abnormalities identified in more than 15% of patients included +3/+3q (37%), 7q deletions (31%), +18/+18q (28%), 6q deletions (19%), +12/+12q (15%) and 8p deletions (15%). Trisomy 3/3q, 7q deletions, +18 and +12 were seen in different combinations in more than 30% of patients in comparison to 2% in lymphocytic lymphomas/chronic lymphocytic leukemias, 1% in mantle cell lymphomas and 7% in follicular lymphomas. The marked propensity of these abnormalities to be recurrently associated with the same tumoral clone of individual karyotypes allowed the delineation of a cytogenetic profile that may help to distinguish non-MALT MZL among other mature B-cell neoplasms. If +3/3q, +12/+12q, and 6q, 7q and 8p deletions were significantly associated with clinical prognostic factors previously reported to influence survival and time to progression, patients displaying these abnormalities did not experience a significantly shorter time to progression.

Adult↗
PubMed2004

Prognostic factors in patients with aggressive non-Hodgkin's lymphoma treated by front-line autotransplantation after complete remission: a cohort study by the Groupe d'Etude des Lymphomes de l'Adulte.

PURPOSE: Improved survival has been observed in aggressive non-Hodgkin's lymphoma (NHL) patients with adverse prognostic factors when autotransplantation (ASCT) was performed after complete remission. However, there is no agreement on the prognostic factors for patients treated with ASCT. We aimed to estimate the prognostic effect of clinical and biologic variables on relapse and survival rates by pooling the data from two trials. PATIENTS AND METHODS: Of the patients treated in the LNH87 and LNH93 trials, 330 under age 60 years achieved complete remission after high-dose cyclophosphamide, doxorubicin, vincristine, and prednisone, and received consolidative ASCT; 16% of patients had T-cell NHL. The International Prognostic Index (IPI) score was 0 for 11%, 1 for 23%, 2 for 51%, and 3 for 15%. Univariate and Cox multivariate survival analyses were retrospectively performed on this population. RESULTS: Overall survival was 75 +/- 5% at 5 years and disease-free survival (DFS) 67 +/- 5%. For T-cell NHL, these scores were 54% and 44%, respectively. The IPI score had no prognostic value and only the following parameters adversely affected overall survival and DFS (P <.05): marrow involvement; more than one extranodal site; histology (nonanaplastic T-cell v others); and type of anthracycline (mitoxantrone v doxorubicin, for DFS only). CONCLUSION: These results suggest that ASCT can prevent relapse in patients with adverse IPI factors. However, patients presenting with a nonanaplastic T-cell phenotype, more than one extranodal site, or marrow involvement still have a higher risk of relapse. These factors should be taken into account when designing post-ASCT maintenance studies.

Adolescent↗
PubMed2004

Subclinical late cardiomyopathy after doxorubicin therapy for lymphoma in adults.

PURPOSE: To assess the cardiac status of the long-term survivors and to estimate the incidence and the features of subclinical cardiotoxicity induced after conventional treatment with doxorubicin for non-Hodgkin's lymphoma or Hodgkin's lymphoma. PATIENTS AND METHODS: We analyzed a group of patients who previously received doxorubicin-based chemotherapy for lymphoma. Echocardiograms were performed at least 5 years after therapy with anthracyclines. Clinical cardiomyopathy was defined by the presence of clinical signs of congestive heart failure (CHF). Subclinical cardiomyopathy was defined by decrease of left ventricular fractional shortening (FS) without clinical signs of CHF. Cumulative dose of doxorubicin, male sex, older age, relapse, radiotherapy (mediastinal or total-body irradiation), autologous stem-cell transplantation, high-dose cyclophosphamide, and cardiovascular risk factors (hypertension, diabetes, hypercholesterolemia, familial history of cardiac disease, being overweight, and smoking history) were evaluated as potential risk factors for the development of cardiac dysfunction. RESULTS: Of 141 assessable patients (median age, 54 years; median cumulative dose of doxorubicin, 300 mg/m(2)), only one developed CHF. Criteria of subclinical cardiomyopathy were found in 39 patients. In multivariate analysis, factors that contributed to decreased FS were male sex (P <.01), older age (P <.01), higher cumulative dose of doxorubicin or association with another anthracycline (P =.04), radiotherapy (P =.04), and being overweight (P =.04). CONCLUSION: Cardiac abnormalities can occur in patients treated with doxorubicin for lymphoma in the absence of CHF, even in patients who received moderate anthracycline doses. Male sex, older age, higher dose of doxorubicin, radiotherapy, and being overweight were risk factors for the development of cardiomyopathy.

Adult↗
PubMed2004

All aggressive lymphoma subtypes do not share similar outcome after front-line autotransplantation: a matched-control analysis by the Groupe d'Etude des Lymphomes de l'Adulte (GELA).

BACKGROUND: Data are still conflicting on the indication of front-line autologous stem-cell transplantation (ASCT) as consolidation for aggressive lymphoma. To assess the therapeutic effect of ASCT among different aggressive lymphoma subtypes, we conducted a matched-control analysis by pooling the data from two Groupe d'Etude des Lymphomes de l'Adulte (GELA) trials. PATIENTS AND METHODS: Between October 1987 and September 1998, 330 patients received ASCT after achieving complete remission with the ACBVP induction regimen. The histological slides showed: B aggressive non-Hodgkin's lymphoma (B-NHL) in 249 patients (75%), T-NHL in 52 patients (15%) (including 23 T anaplastic) and non-classified NHL in 29 patients. The age-adjusted International Prognostic Index (aaIPI) was 2 or 3 in 66%. Patients were matched with controls from the same GELA database but treated with chemotherapy only. RESULTS: ASCT did not benefit non-anaplastic T-NHL patients [5-year overall survival (OS) 44% (chemotherapy) versus 49% (ASCT), P=0.87; disease-free survival (DFS) 38% versus 45%, P=0.89] in comparison with B-NHL [5-year OS 77% (chemotherapy) versus 79% (ASCT), P=0.64; DFS 67% versus 72%, P=0.13]. However, for B-NHL patients with aaIPI score 2 or 3, the benefit of ASCT was significant. CONCLUSIONS: This cohort study confirms the high efficacy of front-line ASCT in responding aggressive B-NHL patients with adverse prognostic factors.

Adolescent↗
PubMed2003

T-cell/histiocyte-rich large B-cell lymphomas and classical diffuse large B-cell lymphomas have similar outcome after chemotherapy: a matched-control analysis.

PURPOSE: Because it is unclear whether T-cell/histiocyte-rich large B-cell lymphomas (H/TCRBCL) should be considered as a true clinicopathologic entity, we conducted a matched-control analysis comparing patients with H/TCRBCL and patients with diffuse large-B cell lymphoma (B-DLCL). PATIENTS AND METHODS: More than 4,500 patients were enrolled onto non-Hodgkin's lymphoma trials conducted by the Groupe d'Etude des Lymphomes de l'Adulte. After histologic review, 50 patients were subclassified as H/TCRBCL. They were matched to 150 patients with B-DLCL for each of the factors of the International Prognostic Index (IPI). RESULTS: Clinical characteristics of H/TCRBCL patients showed a male predominance and a median age of 47 years. Performance status was normal in 89% of patients, whereas lactate dehydrogenase level was increased in 60% of patients. The disease was disseminated in 81% of patients, and 48% had two or more involved extranodal sites. The IPI score was >or= 2 in 53% of patients. The complete response rate to chemotherapy was 63%, and 5-year overall survival (OS) and event-free survival (EFS) rates (mean +/- SD) were 58% +/- 18% and 53% +/- 16%, respectively. The matched-control analysis showed a trend toward a better response to chemotherapy for patients with B-DLCL (P =.06), whereas no difference was observed in OS (P =.9) and EFS (P =.8). CONCLUSION: H/TCRBCL is an aggressive disease that often presents with adverse prognostic factors. However, when treatment is adapted to the disease risk, outcome is equivalent to that observed in patients with B-DLCL. Thus H/TCRBCL should be considered a pathologic variant that belongs to the B-DLCL category.

Adult↗
PubMed2003

Autoimmune thrombocytopenic purpura after autologous stem cell transplantation.

The pathogenesis of thrombocytopenia occurring after autologous stem cell transplantation (ASCT) remains unclear. Six cases of classical peripheral thrombocytopenia that developed after ASCT for non-Hodgkin's lymphoma (NHL) are presented. Resolution of this complication was obtained by usual treatment such as steroids, splenectomy or progressively resolved without specific treatment. Five out of six patients have been followed for more than 5 years after hematopoietic transplantation and are still alive in complete remission despite poor prognostic factors at diagnosis. Several arguments suggest that this phenomenon represents autoimmune thrombocytopenia and may be the consequence of an altered immune balance. Consequently, development of autoimmune reactions after bone marrow transplantation might be associated with an antitumoral effect (graft-versus-lymphoma effect).

Adult↗
PubMed2002

Multifocal progressive leukoencephalopathy occurring after refractory anemia and multiple infectious disorders consecutive to severe lymphopenia.

Progressive multifocal leukoencephalopathy (PML) is related to central nervous system infection with JC virus (JCV). This leukoencephalopathy occurs in immunocompromised patients such as those with acquired immunodeficiency syndrome (AIDS) or lymphoid malignancies. We describe here a patient with myelodysplastic syndrome who developed several life-threatening infections including listeriosis, tuberculosis, and PML. Listeriosis and recurrence of tuberculosis preceded the occurrence of PML. Neurologic features associated with major ataxia, speech disorders, and PML were documented by cranial magnetic resonance imaging showing typical features in the cerebellum and proven by polymerase chain reaction (PCR) detection of JCV DNA in the cerebrospinal fluid. No specific treatment was decided because of progression toward acute myeloid leukemia. In this case, PML occurred with no susceptibility and without immunosuppressive treatment. Our case adds further support to the association between the impairment of T-cell immune responses and myelodysplastic disorders.

Anemia, Refractory↗
PubMed2002

Amifostine reduces mucosal damage after high-dose melphalan conditioning and autologous peripheral blood progenitor cell transplantation for patients with multiple myeloma.

High-dose melphalan (HDM) has been adopted as standard therapy in the treatment of multiple myeloma. This treatment is associated with non-selective cytotoxicity, causing oral mucositis as the major non-hematological side-effect. Amifostine is a cytoprotector which prevents toxicity induced by anticancer therapy. We prospectively compared two groups of patients who either received (group A, n = 21) or did not receive (group B, n = 20) amifostine (740 mg/m(2)) before HDM (200 mg/m(2)) followed by autologous peripheral blood progenitor cell transplantation. The occurrence of severe oral mucositis was significantly decreased in group A in comparison to group B (33% vs 65%, P < 0.05). Six patients in group A required opioid analgesic therapy during a mean period of 4.8 days as compared to eight patients for 6.5 days in group B (P = NS). Delayed vomiting was less frequent in group A (43% vs 70%, P = 0.07) and significantly less severe in group A (grade 2-4) vomiting: two patients vs nine patients, P < 0.02). No difference was observed between the two groups in either hematological toxicity after HDM or in response rate. Grade I emesis was the only immediate side-effect observed after amifostine administration. We conclude that amifostine can reduce mucositis induced by HDM.

Adult↗
PubMed2002

Primary thyroid lymphoma is a heterogeneous disease.

We retrospectively analyzed 26 patients with thyroid lymphoma (TL). Patients were mostly females, with a median age of 59 yr, presenting a rapidly growing nodular goiter with or without cervical adenopathy, without symptoms related to lymphoma for 81% and hypothyroidism in 61%. A previous history of Hashimoto thyroiditis was observed in 11 patients. Six different subtypes of lymphoma were observed: 13 of 26 (50%) had diffuse large B cell lymphoma, 6 (23%) mucosa- associated lymphoid tissue (MALT) lymphoma, 3 (12%) had follicular lymphoma, 2 (7%) had Hodgkin's disease, 1 (4%) had small lymphocytic lymphoma, and 1 (4%) had Burkitt's lymphoma. Diffuse large B cell lymphoma patients presented a compressive multinodular goiter, cervical adenopathy (66%), disseminated disease (50%), and poor performance status, with a poor prognosis (5-yr survival at 44%) despite a treatment based on a multidrug regimen. MALT lymphoma arose in patients with previous history of Hashimoto disease, was localized in all but 1, and was biologically associated with hypothyroidism and a high level of serum antithyroid antibodies. With total thyroidectomy, prognosis was good (5-yr survival at 100%). We did not find any routine clinical or biological parameters that could predict the evolution from Hashimoto's thyroiditis to MALT lymphoma. In conclusion, we confirmed the histological heterogeneity of TL corresponding to different clinical presentations and different prognoses.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

The superoxide dismutase content in erythrocytes predicts short-term toxicity of high-dose cyclophosphamide.

Patients receiving high-dose cyclophosphamide as a conditioning regimen for peripheral stem cell collection are subjected over a short period of time to significant exposure to reactive oxygen species (ROS). All these patients undergo profound leucopenia. Various other short-term toxicities are observed in a fraction of the patients, including febrile aplasia requiring hospitalization, thrombocytopenia and mucositis. Although stem cell collection is feasible in the majority of patients stimulated with haematopoietic growth factors, in some instances, graft collection cannot be performed because of insufficient concentrations of stem cells in peripheral blood. There is currently no predictive assay to determine which patients treated with high-dose cyclophosphamide have a high risk of febrile aplasia or will successfully undergo cytaphereses for stem cell collection. In order to identify such predictive factors, we analysed the level of expression before treatment of various ROS detoxification mechanisms in the peripheral blood of 37 patients receiving high-dose cyclophosphamide for lymphoproliferative diseases. Various parameters involved in the metabolism of ROS were measured in plasma and/or erythrocytes, including superoxide dismutase, glutathione, glutathione peroxidase, glutathione reductase and malondialdehyde. High levels of erythrocyte superoxide dismutase before cyclophosphamide therapy were correlated with an increased risk of hospitalization for febrile aplasia (65% vs. 29%, P = 0.013). High superoxide dismutase and low erythrocyte glutathione reductase were associated with lower CD34 yields. These data suggest that components of the ROS detoxification system modulate the degree of short-term toxicity of cyclophosphamide and could be used as predictive markers in individual patients.

Adult↗
PubMed2001

Gemcitabine as a single agent in the treatment of relapsed or refractory low-grade non-Hodgkin's lymphoma.

A multicentre phase II trial was conducted to evaluate the efficacy and toxicity of gemcitabine in patients with refractory or relapsed indolent non-Hodgkin's lymphoma. Thirty-six patients were enrolled onto the study, including 11 cases of mantle cell lymphoma (MCL), 10 cases of chronic lymphocytic leukaemia (CLL)/lymphocytic lymphoma, nine cases of follicular lymphoma, four cases of lymphoplasmacytic lymphoma and two cases of T-cell lymphoma. Gemcitabine 1 g/m(2) was administered as a 30-min infusion on d 1, 8 and 15 of a 28-d schedule, up to a maximum of six cycles. Complete responses were observed in two patients with MCL, and partial responses were observed in seven patients, including three patients with CLL/lymphocytic lymphoma, two patients with T-cell lymphoma, one patient with MCL and one patient with follicular lymphoma. Minor responses were observed in three patients, including two patients with MCL and one patient with CLL. The median duration of response was 150 d and the overall progression-free survival was 342 d. Haematological toxicity was observed as grade 3-4 leucopenia in 12 patients (33%) and grade 3-4 thrombocytopenia in 18 patients (50%). Severe non-haematological toxicity included one case of fatal veno-occlusive disease, one case of thrombotic microangiopathy leading to terminal renal failure, one case of capillary leak syndrome, one case of myocardial infarction and drug-induced fever in two patients. These data suggest that gemcitabine displays activity in patients with MCL and CLL/lymphocytic lymphoma. Haematological toxicity was frequent in these heavily treated patients. Severe non-haematological toxicity was significant and should be taken into account in the design of future trials.

Adult↗
PubMed2000

Detection of differentially expressed genes in lymphomas using cDNA arrays: identification of clusterin as a new diagnostic marker for anaplastic large-cell lymphomas.

This study reports the first use of gene array technology for the identification of a tumor-specific marker in lymphoid neoplasms. The differential gene expression of 31 hematopoietic cell lines, representing most major lymphoma subgroups of B- and T-cell origin, was assessed by hybridizing labeled complementary DNA to Atlas human expression arrays containing 588 genes. Genes known to be specific for B, T, or myelomonocytic lineages were appropriately identified in the arrays, validating the general utility of this approach. One gene, clusterin, not previously known to be expressed in lymphoid neoplasms, was specifically found in all 4 anaplastic large-cell lymphoma (ALCL) cell lines, but not in any of the 27 remaining tumor lines. Using a monoclonal antibody against clusterin, its differential expression was confirmed by Western blotting and immunohistochemistry. A total of 198 primary lymphomas (representing most major lymphoma subtypes), including 36 cases of systemic ALCL, were surveyed for clusterin expression by immunohistochemistry and Western blotting. All of the 36 ALCL cases marked for clusterin, with most cases showing moderate to strong staining in the majority of neoplastic cells. Clusterin expression was not related to expression of anaplastic lymphoma kinase-1. With 2 exceptions, none of the remaining 162 non-ALCL cases marked with the clusterin antibody, including Hodgkin disease and primary cutaneous ALCL. In reactive lymphoid tissues, only follicular dendritic cells and fibroblastic reticular cells exhibited staining. Clusterin is a highly conserved glycoprotein implicated in intercellular and cell matrix interactions, regulation of the complement system, lipid transport, stress responses, and apoptosis. Although its function in ALCL is unknown, the unique expression of clusterin within this category of lymphoma provides an additional marker for the diagnosis of ALCL. This study illustrates the enormous potential of gene array technologies for diagnostic marker discovery. (Blood. 2000;96:398-404)

Biomarkers, Tumor↗