22 results on '"Molina TJ"'
Search Results
2. Lymph node excisions provide more precise lymphoma diagnoses than core biopsies: a French Lymphopath network survey.
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Syrykh C, Chaouat C, Poullot E, Amara N, Fataccioli V, Parrens M, Traverse-Glehen A, Molina TJ, Xerri L, Martin L, Dubois R, Lacheretz-Szablewski V, Copin MC, Moreau A, Chenard MP, Cabarrou B, Lusque A, Gaulard P, Brousset P, and Laurent C
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- Humans, Female, Biopsy, Large-Core Needle methods, Lymph Node Excision, Lymph Nodes surgery, Lymph Nodes pathology, Biopsy, Retrospective Studies, Multicenter Studies as Topic, Lymphoma diagnosis, Lymphoma surgery, Lymphoma pathology, Breast Neoplasms pathology
- Abstract
According to expert guidelines, lymph node surgical excision is the standard of care for lymphoma diagnosis. However, core needle biopsy (CNB) has become widely accepted as part of the lymphoma diagnostic workup over the past decades. The aim of this study was to present the largest multicenter inventory of lymph nodes sampled either by CNB or surgical excision in patients with suspected lymphoma and to compare their diagnostic performance in routine pathologic practice. We reviewed 32 285 cases registered in the French Lymphopath network, which provides a systematic expert review of all lymphoma diagnoses in France, and evaluated the percentage of CNB and surgical excision cases accurately diagnosed according to the World Health Organization classification. Although CNB provided a definitive diagnosis in 92.3% and seemed to be a reliable method of investigation for most patients with suspected lymphoma, it remained less conclusive than surgical excision, which provided a definitive diagnosis in 98.1%. Discordance rates between referral and expert diagnoses were higher on CNB (23.1%) than on surgical excision (21.2%; P = .004), and referral pathologists provided more cases with unclassified lymphoma or equivocal lesion through CNB. In such cases, expert review improved the diagnostic workup by classifying ∼90% of cases, with higher efficacy on surgical excision (93.3%) than CNB (81.4%; P < 10-6). Moreover, diagnostic concordance for reactive lesions was higher on surgical excision than CNB (P = .009). Overall, although CNB accurately diagnoses lymphoma in most instances, it increases the risk of erroneous or nondefinitive conclusions. This large-scale survey also emphasizes the need for systematic expert review in cases of lymphoma suspicion, especially in those sampled by using CNB., (© 2022 by The American Society of Hematology.)
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- 2022
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3. The alternative RelB NF-κB subunit is a novel critical player in diffuse large B-cell lymphoma.
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Eluard B, Nuan-Aliman S, Faumont N, Collares D, Bordereaux D, Montagne A, Martins I, Cagnard N, Caly M, Taoui O, Lordello L, Lehmann-Che J, Tesson B, Martinez-Climent JA, Copie-Bergman C, Haioun C, Tilly H, Bonsang B, Vincent-Salomon A, Jais JP, Jardin F, Leroy K, Maiuri MC, Kroemer G, Molina TJ, Feuillard J, and Baud V
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- Apoptosis, Cell Line, Tumor, Gene Expression Regulation, Neoplastic, Humans, Lymphoma, Large B-Cell, Diffuse genetics, NF-kappa B genetics, Transcription Factor RelB genetics, Transcriptional Activation, Lymphoma, Large B-Cell, Diffuse metabolism, NF-kappa B metabolism, Transcription Factor RelB metabolism
- Abstract
Diffuse large B-cell lymphoma (DLBCL) is the most frequent lymphoid malignancy affecting adults. The NF-κB transcription factor family is activated by 2 main pathways, the canonical and the alternative NF-κB activation pathway, with different functions. The alternative NF-κB pathway leads to activation of the transcriptionally active RelB NF-κB subunit. Alternative NF-κB activation status and its role in DLBCL pathogenesis remain undefined. Here, we reveal a frequent activation of RelB in a large cohort of DLBCL patients and cell lines, independently of their activated B-cell-like or germinal center B-cell-like subtype. RelB activity defines a new subset of patients with DLBCL and a peculiar gene expression profile and mutational pattern. Importantly, RelB activation does not correlate with the MCD genetic subtype, enriched for activated B-cell-like tumors carrying MYD88L265P and CD79B mutations that cooperatively activate canonical NF-κB, thus indicating that current genetic tools to evaluate NF-κB activity in DLBCL do not provide information on the alternative NF-κB activation. Furthermore, the newly defined RelB-positive subgroup of patients with DLBCL exhibits a dismal outcome after immunochemotherapy. Functional studies revealed that RelB confers DLBCL cell resistance to DNA damage-induced apoptosis in response to doxorubicin, a genotoxic agent used in the front-line treatment of DLBCL. We also show that RelB positivity is associated with high expression of cellular inhibitor of apoptosis protein 2 (cIAP2). Altogether, RelB activation can be used to refine the prognostic stratification of DLBCL and may contribute to subvert the therapeutic DNA damage response in a segment of patients with DLBCL., (© 2022 by The American Society of Hematology.)
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- 2022
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4. RADIORYTHMIC: Phase III, Opened, Randomized Study of Postoperative Radiotherapy Versus Surveillance in Stage IIb/III of Masaoka Koga Thymoma after Complete Surgical Resection.
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Basse C, Botticella A, Molina TJ, Falcoz PE, Oulkhouir Y, Kerjouan M, Pichon E, Westeel V, Thiberville L, Quantin X, Clément-Duchêne C, Khalifa J, Tinier FL, Ginoux M, Thillays F, Mordant P, Besse B, Thomas PA, Péchoux CL, and Girard N
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- Adolescent, Adult, Aged, Humans, Middle Aged, Neoplasm Staging, Postoperative Period, Prognosis, Retrospective Studies, Thymoma surgery, Thymus Neoplasms surgery, Young Adult, Thymoma pathology, Thymoma radiotherapy, Thymus Neoplasms pathology, Thymus Neoplasms radiotherapy
- Abstract
Introduction: Thymomas are rare intrathoracic malignancies that may be aggressive and difficult to treat. Knowledge and level of evidence for treatment strategies are mainly based on retrospective studies or expert opinion. Currently there is no strong evidence that postoperative radiotherapy after complete resection of localized thymoma is associated with survival benefit in patients. RADIORYTHMIC is a phase III, randomized trial aiming at comparing postoperative radiotherapy versus surveillance after complete resection of Masaoka-Koga stage IIb/III thymoma. Systematic central pathologic review will be performed before patient enrollment as per the RYTHMIC network pathway., Patients and Methods: Three hundred fourteen patients will be included; randomization 1:1 will attribute either postoperative radiotherapy (50-54 Gy to the mediastinum using intensity-modulated radiation therapy or proton beam therapy) or surveillance. Stratification criteria include histologic grading (thymoma type A, AB, B1 vs B2, B3), stage, and delivery of preoperative chemotherapy. Patient recruitment will be mainly made through the French RYTHMIC network of 15 expert centers participating in a nationwide multidisciplinary tumor board. Follow-up will last 7 years. The primary endpoint is recurrence-free survival. Secondary objectives include overall survival, assessment of acute and late toxicities, and analysis of prognostic and predictive biomarkers., Results: The first patient will be enrolled in January 2021, with results expected in 2028., (Copyright © 2021 Elsevier Inc. All rights reserved.)
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- 2021
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5. Obinutuzumab vs rituximab for advanced DLBCL: a PET-guided and randomized phase 3 study by LYSA.
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Le Gouill S, Ghesquières H, Oberic L, Morschhauser F, Tilly H, Ribrag V, Lamy T, Thieblemont C, Maisonneuve H, Gressin R, Bouhabdallah K, Haioun C, Damaj G, Fornecker L, Bouhabdallah R, Feugier P, Sibon D, Cartron G, Bonnet C, André M, Chartier L, Ruminy P, Kraeber-Bodéré F, Bodet-Milin C, Berriolo-Riedinger A, Brière J, Jais JP, Molina TJ, Itti E, and Casasnovas RO
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- Antibodies, Monoclonal, Humanized, Cyclophosphamide therapeutic use, Doxorubicin therapeutic use, Humans, Positron-Emission Tomography, Prednisone therapeutic use, Rituximab therapeutic use, Vincristine therapeutic use, Antineoplastic Combined Chemotherapy Protocols, Lymphoma, Large B-Cell, Diffuse drug therapy
- Abstract
Rituximab plus polychemotherapy is the standard of care in diffuse large B-cell lymphoma (DLBCL). GAINED, a randomized phase 3 trial, compared obinutuzumab to rituximab. Transplant-eligible patients (18-60 years) with an untreated age-adjusted International Prognostic Index (aaIPI) score ≥1 DLBCL were randomized (1:1) between obinutuzumab or rituximab and stratified by aaIPI (1; 2-3) and chemotherapy regimen (doxorubicin, cyclophosphamide, prednisone plus vindesine, bleomycin [ACVBP] or vincristine [CHOP]). Consolidation treatment was determined according to response to interim positron emission tomography (PET). Responders after cycle 2 and 4 (PET2-/PET4-) received immunochemotherapy. Responders after only cycle 4 (PET2+/4-) received transplantation. The primary objective was an 8% improvement (hazard ratio [HR] = 0.73; 80% power; α risk, 2.5%; 1-sided) in 2-year event-free survival (EFS) in the obinutuzumab arm. From September 2012, 670 patients were enrolled (obinutuzumab, n = 336; rituximab, n = 334). A total of 383 (57.2%) were aaIPI 2-3, 339 (50.6%) received CHOP. Median follow-up was 38.7 months. The 2-year EFS was similar in both groups (59.8% vs 56.6%; P = .123; HR = 0.88). The 2-year PFS in the whole cohort was 83.1% (95% confidence interval, 80% to 85.8%). PET2-/4- and PET2+/4- had similar 2-year progression-free survival (PFS) and overall survival (OS): 89.9% vs 83.9% and 94.8% vs 92.8%. The 2-year PFS and OS for PET4+ patients were 62% and 83.1%. Grade 3-5 infections were more frequent in the obinutuzumab arm (21% vs 12%). Obinutuzumab is not superior to rituximab in aaIPI ≥1 DLBCL transplant-eligible patients. This trial was registered at www.clinicaltrials.gov as #NCT01659099., (© 2021 by The American Society of Hematology.)
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- 2021
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6. Mutational landscape of gray zone lymphoma.
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Sarkozy C, Hung SS, Chavez EA, Duns G, Takata K, Chong LC, Aoki T, Jiang A, Miyata-Takata T, Telenius A, Slack GW, Molina TJ, Ben-Neriah S, Farinha P, Dartigues P, Damotte D, Mottok A, Salles GA, Casasnovas RO, Savage KJ, Laurent C, Scott DW, Traverse-Glehen A, and Steidl C
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Epstein-Barr Virus Infections complications, Epstein-Barr Virus Infections genetics, Female, Hodgkin Disease complications, Humans, Lymphoma, Large B-Cell, Diffuse complications, Male, Mediastinal Neoplasms complications, Middle Aged, Thymus Gland metabolism, Young Adult, Hodgkin Disease genetics, Lymphoma, Large B-Cell, Diffuse genetics, Mediastinal Neoplasms genetics, Mutation
- Abstract
The mutational landscape of gray zone lymphoma (GZL) has not yet been established, and differences from related entities are largely unknown. Here, we studied coding sequence mutations of 50 Epstein-Barr virus (EBV)-negative GZLs and 20 polymorphic EBV+ diffuse large B-cell lymphoma (DLBCL) not otherwise specified (poly-EBV-L) in comparison with classical Hodgkin lymphoma (cHL), primary mediastinal large B-cell lymphoma (PMBCL), and DLBCL. Exomes of 21 GZL and 7 poly-EBV-L cases, along with paired constitutional DNA, were analyzed as a discovery cohort, followed by targeted sequencing of 217 genes in an extension cohort of 29 GZL and 13 poly-EBV-L cases. GZL cases with thymic niche involvement (anterior mediastinal mass) exhibited a mutation profile closely resembling cHL and PMBCL, with SOCS1 (45%), B2M (45%), TNFAIP3 (35%), GNA13 (35%), LRRN3 (32%), and NFKBIA (29%) being the most recurrently mutated genes. In contrast, GZL cases without thymic niche involvement (n = 18) had a significantly distinct pattern that was enriched in mutations related to apoptosis defects (TP53 [39%], BCL2 [28%], BIRC6 [22%]) and depleted in GNA13, XPO1, or NF-κB signaling pathway mutations (TNFAIP3, NFKBIE, IKBKB, NFKBIA). They also exhibited more BCL2/BCL6 rearrangements compared with thymic GZL. Poly-EBV-L cases presented a distinct mutational profile, including STAT3 mutations and a significantly lower coding mutation load in comparison with EBV- GZL. Our study highlights characteristic mutational patterns in GZL associated with presentation in the thymic niche, suggesting a common cell of origin and disease evolution overlapping with related anterior mediastinal lymphomas., (© 2021 by The American Society of Hematology.)
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- 2021
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7. Concurrent cerebral aspergillosis and abdominal mucormycosis during ibrutinib therapy for chronic lymphocytic leukaemia.
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Pouvaret A, Guery R, Montillet M, Molina TJ, Duréault A, Bougnoux ME, Galliot R, Lanternier F, Delarue R, and Lortholary O
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- Adenine analogs & derivatives, Adult, Humans, Neoplasm Recurrence, Local, Nervous System, Piperidines, Pyrazoles, Pyrimidines, Aspergillosis, Leukemia, Lymphocytic, Chronic, B-Cell, Mucormycosis
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- 2019
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8. Authors' Reply.
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Bobée V, Ruminy P, Marchand V, Viailly PJ, Abdel Sater A, Veresezan L, Drieux F, Bérard C, Bohers E, Mareschal S, Dubois S, Jais JP, Leroy K, Figeac M, Picquenot JM, Molina TJ, Salles G, Haioun C, Tilly H, and Jardin F
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- Adenine analogs & derivatives, Mutation, Piperidines, Pyrazoles, Pyrimidines, Myeloid Differentiation Factor 88
- Abstract
Authors' Reply to the Letter to the Editor by Y. Lynn Wang (MYD88 mutations and sensitivity to ibrutinib therapy)., (Copyright © 2018 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2018
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9. Determination of Molecular Subtypes of Diffuse Large B-Cell Lymphoma Using a Reverse Transcriptase Multiplex Ligation-Dependent Probe Amplification Classifier: A CALYM Study.
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Bobée V, Ruminy P, Marchand V, Viailly PJ, Abdel Sater A, Veresezan L, Drieux F, Bérard C, Bohers E, Mareschal S, Dubois S, Jais JP, Leroy K, Figeac M, Picquenot JM, Molina TJ, Salles G, Haioun C, Tilly H, and Jardin F
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- Biomarkers, Tumor genetics, Gene Expression Profiling, Gene Expression Regulation, Neoplastic genetics, Humans, Lymphoma, Large B-Cell, Diffuse classification, Lymphoma, Large B-Cell, Diffuse diagnosis, Lymphoma, Large B-Cell, Diffuse pathology, Mutation, Paraffin Embedding, Lymphoma, Large B-Cell, Diffuse genetics, Multiplex Polymerase Chain Reaction methods, Oligonucleotide Array Sequence Analysis methods, Reverse Transcriptase Polymerase Chain Reaction methods
- Abstract
Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma. It includes three major subtypes termed germinal center B-cell-like, activated B-cell-like, and primary mediastinal B-cell lymphoma. With the emergence of novel targeted therapies, accurate methods capable of interrogating this cell-of-origin classification should soon become essential in the clinics. To address this issue, we developed a novel gene expression profiling DLBCL classifier based on reverse transcriptase multiplex ligation-dependent probe amplification. This assay simultaneously evaluates the expression of 21 markers, to differentiate primary mediastinal B-cell lymphoma, activated B-cell-like, germinal center B-cell-like, and also Epstein-Barr virus-positive DLBCLs. It was trained using 70 paraffin-embedded biopsies and validated using >160 independent samples. Compared with a reference classification established from Affymetrix U133 + 2 data, reverse transcriptase multiplex ligation-dependent probe amplification classified 85.0% samples into the expected subtype, comparing favorably with current diagnostic methods. This assay also proved to be highly efficient in detecting the MYD88 L265P mutation, even in archival paraffin-embedded tissues. This reliable, rapid, and cost-effective method uses common instruments and reagents and could thus easily be implemented into routine diagnosis workflows, to improve the management of these aggressive tumors., (Copyright © 2017 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2017
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10. BCL2 expression but not MYC and BCL2 coexpression predicts survival in elderly patients with diffuse large B-cell lymphoma independently of cell of origin in the phase 3 LNH03-6B trial.
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Petrella T, Copie-Bergman C, Brière J, Delarue R, Jardin F, Ruminy P, Thieblemont C, Figeac M, Canioni D, Feugier P, Fabiani B, Leroy K, Parrens M, André M, Haioun C, Salles GA, Gaulard P, Tilly H, Jais JP, and Molina TJ
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- Aged, Aged, 80 and over, Antibodies, Monoclonal, Murine-Derived administration & dosage, Antibodies, Monoclonal, Murine-Derived adverse effects, Antineoplastic Combined Chemotherapy Protocols adverse effects, Biomarkers, Tumor genetics, Cyclophosphamide administration & dosage, Cyclophosphamide adverse effects, Disease-Free Survival, Doxorubicin administration & dosage, Doxorubicin adverse effects, Female, Gene Expression Regulation, Neoplastic drug effects, Humans, Lymphoma, Large B-Cell, Diffuse genetics, Lymphoma, Large B-Cell, Diffuse pathology, Male, Middle Aged, Prednisone administration & dosage, Prednisone adverse effects, Prognosis, Risk Factors, Rituximab, Treatment Outcome, Vincristine administration & dosage, Vincristine adverse effects, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Lymphoma, Large B-Cell, Diffuse drug therapy, Proto-Oncogene Proteins c-bcl-2 genetics, Proto-Oncogene Proteins c-myc genetics
- Abstract
Background: Our aim was to evaluate whether the cell of origin (COO) as defined by the Hans algorithm and MYC/BCL2 coexpression, which are the two main biological risk factors in elderly patients treated with rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisolone (R-CHOP), maintain their prognostic value in a large prospective clinical trial., Patients and Methods: We evaluated 285 paraffin-embedded samples from patients (60-80 years of age) enrolled in the Lymphoma Study Association trial LNH03-6B who were treated with R-CHOP. We correlated the COO defined by the transcriptome according to the Wright algorithm with that defined by the Hans algorithm in a subset of 62 tumors with available frozen tissue samples., Results: The non-germinal center B-cell-like phenotype according to the Hans algorithm and BCL2 expression (but not MYC and BCL2 coexpression) predicted worse progression-free survival [hazard ratio (HR)=1.78, P = 0.003 and HR = 1.79, P = 0.003, respectively] and overall survival (HR = 1.85, P = 0.005 and HR = 1.67, P = 0.02, respectively) independently of the International Prognostic Index. The correlation between the Hans algorithm and the Wright algorithm was 91%, with an almost perfect concordance according to a kappa test (0.81)., Conclusions: Our results suggest that immunohistochemically defined COO remains a useful tool for predicting prognosis in diffuse large B-cell lymphoma when performed under optimized standardized conditions and that BCL2 expression may help to identify elderly patients at risk for relapse and who could potentially respond to anti-BCL2 targeted agents. In this prospective phase III trial, the coexpression of MYC and BCL2 does not appear to predict worse survival., Clinical Trial Number: NCT00144755., (© The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
- Published
- 2017
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11. MYC-IG rearrangements are negative predictors of survival in DLBCL patients treated with immunochemotherapy: a GELA/LYSA study.
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Copie-Bergman C, Cuillière-Dartigues P, Baia M, Briere J, Delarue R, Canioni D, Salles G, Parrens M, Belhadj K, Fabiani B, Recher C, Petrella T, Ketterer N, Peyrade F, Haioun C, Nagel I, Siebert R, Jardin F, Leroy K, Jais JP, Tilly H, Molina TJ, and Gaulard P
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- Adolescent, Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Murine-Derived administration & dosage, Cyclophosphamide administration & dosage, Disease-Free Survival, Doxorubicin administration & dosage, Female, Humans, Male, Middle Aged, Prednisone administration & dosage, Rituximab, Survival Rate, Vincristine administration & dosage, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Gene Rearrangement, Immunoglobulins genetics, Immunoglobulins metabolism, Lymphoma, Large B-Cell, Diffuse drug therapy, Lymphoma, Large B-Cell, Diffuse genetics, Lymphoma, Large B-Cell, Diffuse metabolism, Lymphoma, Large B-Cell, Diffuse mortality, Proto-Oncogene Proteins c-myc genetics, Proto-Oncogene Proteins c-myc metabolism, Translocation, Genetic
- Abstract
Diffuse large B-cell lymphoma (DLBCL) with MYC rearrangement (MYC-R) carries an unfavorable outcome. We explored the prognostic value of the MYC translocation partner gene in a series of MYC-R de novo DLBCL patients enrolled in first-line prospective clinical trials (Groupe d'Etudes des Lymphomes de l'Adulte/Lymphoma Study Association) and treated with rituximab-anthracycline-based chemotherapy. A total of 774 DLBCL cases characterized for cell of origin by the Hans classifier were analyzed using fluorescence in situ hybridization with BCL2, BCL6, MYC, immunoglobulin (IG)K, and IGL break-apart and IGH/MYC, IGK/MYC, and IGL/MYC fusion probes. MYC-R was observed in 51/574 (8.9%) evaluable DLBCL cases. MYC-R cases were predominantly of the germinal center B-cell-like subtype 37/51 (74%) with no distinctive morphologic and phenotypic features. Nineteen cases were MYC single-hit and 32 cases were MYC double-hit (MYC plus BCL2 and/or BCL6) DLBCL. MYC translocation partner was an IG gene in 24 cases (MYC-IG) and a non-IG gene (MYC-non-IG) in 26 of 50 evaluable cases. Noteworthy, MYC-IG patients had shorter overall survival (OS) (P = .0002) compared with MYC-negative patients, whereas no survival difference was observed between MYC-non-IG and MYC-negative patients. In multivariate analyses, MYC-IG predicted poor progression-free survival (P = .0051) and OS (P = .0006) independently from the International Prognostic Index and the Hans classifier. In conclusion, we show in this prospective randomized trial that the adverse prognostic impact of MYC-R is correlated to the MYC-IG translocation partner gene in DLBCL patients treated with immunochemotherapy. These results may have an important impact on the clinical management of DLBCL patients with MYC-R who should be routinely characterized according to MYC partner gene. These trials are individually registered at www.clinicaltrials.gov as #NCT00144807, #NCT01087424, #NCT00169143, #NCT00144755, #NCT00140660, #NCT00140595, and #NCT00135499., (© 2015 by The American Society of Hematology.)
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- 2015
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12. Accurate Classification of Germinal Center B-Cell-Like/Activated B-Cell-Like Diffuse Large B-Cell Lymphoma Using a Simple and Rapid Reverse Transcriptase-Multiplex Ligation-Dependent Probe Amplification Assay: A CALYM Study.
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Mareschal S, Ruminy P, Bagacean C, Marchand V, Cornic M, Jais JP, Figeac M, Picquenot JM, Molina TJ, Fest T, Salles G, Haioun C, Leroy K, Tilly H, and Jardin F
- Abstract
Diffuse large B-cell lymphoma, the most common non-Hodgkin lymphoma, is subdivided into germinal center B-cell-like and activated B-cell-like subtypes. Unfortunately, these lymphomas are difficult to differentiate in routine diagnosis, impeding the development of treatments. Patients with these lymphomas can benefit from specific therapies. We therefore developed a simple and rapid classifier based on a reverse transcriptase multiplex ligation-dependent probe amplification assay and 14 gene signatures. Compared with the Affymetrix U133+2 gold standard, all 46 samples (95% CI, 92%-100%) of a validation cohort classified by both techniques were attributed to the expected subtype. Similarly, 93% of the 55 samples (95% CI, 82%-98%) of a second independent series characterized with a mid-throughput gene expression profiling method were classified correctly. Unclassifiable sample proportions reached 13.2% and 13.8% in these cohorts, comparable with the frequency originally reported. The developed assay was also sensitive enough to obtain reliable results from formalin-fixed, paraffin-embedded samples and flexible enough to include prognostic factors such as MYC/BCL2 co-expression. Finally, in a series of 135 patients, both overall (P = 0.01) and progression-free (P = 0.004) survival differences between the two subtypes were confirmed. Because the multiplex ligation-dependent probe amplification method is already in use and requires only common instruments and reagents, it could easily be applied to clinical trial patient stratification to help in treatment decisions., (Copyright © 2015 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2015
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13. Defective anti-polysaccharide response and splenic marginal zone disorganization in ALPS patients.
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Neven B, Bruneau J, Stolzenberg MC, Meyts I, Magerus-Chatinet A, Moens L, Lanzarotti N, Weller S, Amiranoff D, Florkin B, Bader-Meunier B, Leverger G, Ferster A, Chantrain C, Blanche S, Picard C, Molina TJ, Brousse N, Durandy A, Rizzi M, Bossuyt X, Fischer A, and Rieux-Laucat F
- Subjects
- Adolescent, Adult, Animals, Autoimmune Lymphoproliferative Syndrome epidemiology, Autoimmune Lymphoproliferative Syndrome surgery, Child, Child, Preschool, Humans, Infant, Infant, Newborn, Mice, Mice, Transgenic, Spleen surgery, Splenectomy adverse effects, Splenectomy statistics & numerical data, Streptococcal Infections epidemiology, Streptococcal Infections immunology, Streptococcus pneumoniae growth & development, Streptococcus pneumoniae immunology, Young Adult, Antibody Formation, Autoimmune Lymphoproliferative Syndrome immunology, Autoimmune Lymphoproliferative Syndrome pathology, Lipopolysaccharides immunology, Spleen immunology, Spleen pathology
- Abstract
Autoimmune lymphoproliferative syndrome (ALPS) caused by impaired FAS-mediated apoptosis of lymphocytes is characterized by lymphoproliferation, autoimmunity, but also an increased risk of invasive bacterial infection, notably following splenectomy. We surveyed a cohort of 100 ALPS patients (including 33 splenectomized) and found that 12 (10 splenectomized) had experienced 23 invasive bacterial infections mainly caused by Streptococcus pneumoniae. This vulnerability was associated with evidence of defective B-cell function characterized by low serum immunoglobulin (Ig) M, low IgM antibody production in response to S pneumoniae following nonconjugated immunization, and low blood memory B-cells counts (including marginal zone [MZ] B-cell counts). This immunodeficiency strongly correlated with intensity of lymphoproliferation. Spleen sections from 9 ALPS patients revealed double-negative T-cell (DN-T) infiltration of the MZ, which was depleted of B cells. MZ in ALPS patients contained an abnormally thick layer of MAdCAM-1((+)) stromal cells and an excess of DN-Ts. DN-Ts were shown to express MAdCAM-1 ligand, the α4β7 integrin. These observations suggest that accumulating DN-Ts are trapped within stromal cell meshwork and interfere with correct localization of MZ B cells. Similar observations were made in spleens of fas-deficient mice. Our data revealed an unexpected mechanism by which ALPS results in anti-polysaccharide IgM antibody production-specific defect. Splenectomy should be avoided., (© 2014 by The American Society of Hematology.)
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- 2014
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14. ITMIG consensus statement on the use of the WHO histological classification of thymoma and thymic carcinoma: refined definitions, histological criteria, and reporting.
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Marx A, Ströbel P, Badve SS, Chalabreysse L, Chan JK, Chen G, de Leval L, Detterbeck F, Girard N, Huang J, Kurrer MO, Lauriola L, Marino M, Matsuno Y, Molina TJ, Mukai K, Nicholson AG, Nonaka D, Rieker R, Rosai J, Ruffini E, and Travis WD
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- Antigens, CD20 analysis, CD5 Antigens analysis, Carcinoma chemistry, Glucose Transporter Type 1 analysis, Humans, Mucin-1 analysis, Proto-Oncogene Proteins c-kit analysis, Reproducibility of Results, Thymoma chemistry, Thymus Neoplasms chemistry, World Health Organization, Carcinoma pathology, Thymoma pathology, Thymus Neoplasms pathology
- Abstract
Introduction: The 2004 version of the World Health Organization classification subdivides thymic epithelial tumors into A, AB, B1, B2, and B3 (and rare other) thymomas and thymic carcinomas (TC). Due to a morphological continuum between some thymoma subtypes and some morphological overlap between thymomas and TC, a variable proportion of cases may pose problems in classification, contributing to the poor interobserver reproducibility in some studies., Methods: To overcome this problem, hematoxylin-eosin-stained and immunohistochemically processed sections of prototypic, "borderland," and "combined" thymomas and TC (n = 72) were studied by 18 pathologists at an international consensus slide workshop supported by the International Thymic Malignancy Interest Group., Results: Consensus was achieved on refined criteria for decision making at the A/AB borderland, the distinction between B1, B2, and B3 thymomas and the separation of B3 thymomas from TCs. "Atypical type A thymoma" is tentatively proposed as a new type A thymoma variant. New reporting strategies for tumors with more than one histological pattern are proposed., Conclusion: These guidelines can set the stage for reproducibility studies and the design of a clinically meaningful grading system for thymic epithelial tumors.
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- 2014
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15. Diffuse large B-cell lymphoma of Waldeyer's ring has distinct clinicopathologic features: a GELA study.
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de Leval L, Bonnet C, Copie-Bergman C, Seidel L, Baia M, Brière J, Molina TJ, Fabiani B, Petrella T, Bosq J, Gisselbrecht C, Siebert R, Tilly H, Haioun C, Fillet G, and Gaulard P
- Subjects
- Anthracyclines therapeutic use, B-Lymphocytes metabolism, B-Lymphocytes pathology, DNA-Binding Proteins metabolism, Disease-Free Survival, Female, Humans, Interferon Regulatory Factors metabolism, Lymphoma, Large B-Cell, Diffuse drug therapy, Lymphoma, Large B-Cell, Diffuse mortality, Male, Middle Aged, Pharyngeal Neoplasms drug therapy, Pharyngeal Neoplasms mortality, Proto-Oncogene Proteins c-bcl-2 metabolism, Proto-Oncogene Proteins c-bcl-6, Proto-Oncogene Proteins c-myc metabolism, Lymphoma, Large B-Cell, Diffuse pathology, Pharyngeal Neoplasms pathology
- Abstract
Background: Diffuse large B-cell lymphomas (DLBCLs) arising in specific extranodal sites have peculiar clinicopathologic features., Patients and Methods: We analyzed a cohort of 187 primary Waldeyer's ring (WR) DLBCLs retrieved from GELA protocols using anthracyclin-based polychemotherapy., Results: Most patients (92%) had stage I-II disease. A germinal center B-cell-like (GCB) immunophenotype was observed in 61%, and BCL2 expression in 55%, of WR DLBCLs. BCL2, BCL6, IRF4 and MYC breakpoints were observed in, respectively, 3 of 42 (7%), 9 of 36 (25%), 2 of 26 (8%) and 4 of 40 (10%) contributive cases. A variable follicular pattern was evidenced in 30 of 68 (44%) large biopsy specimens. The 5-year progression-free survival (PFS) and the overall survival (OS) of 153 WR DLBCL patients with survival information were 69.5% and 77.8%, respectively. The GCB immunophenotype correlated with a better OS (P = 0.0015), while BCL2 expression predicted a worse OS (P = 0.037), an effect overcome by the GCB/non-GCB classification. Compared with matched nodal DLBCLs, WR DLBCLs with no age-adjusted international prognostic index factor disclosed a better 5-year PFS rate (77.5% versus 70.7%; P = 0.03)., Conclusions: WR DLBCLs display distinct clinicopathologic features compared with conventional DLBCLs, with usual localized-stage disease, common follicular features and a high frequency of GCB immunophenotype contrasting with a low rate of BCL2 rearrangements. In addition, they seem to be associated with a better outcome than their nodal counterpart.
- Published
- 2012
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16. Intensified chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab for the treatment of diffuse large B-cell lymphoma (LNH03-2B): an open-label randomised phase 3 trial.
- Author
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Récher C, Coiffier B, Haioun C, Molina TJ, Fermé C, Casasnovas O, Thiéblemont C, Bosly A, Laurent G, Morschhauser F, Ghesquières H, Jardin F, Bologna S, Fruchart C, Corront B, Gabarre J, Bonnet C, Janvier M, Canioni D, Jais JP, Salles G, and Tilly H
- Subjects
- Adolescent, Adult, Antineoplastic Combined Chemotherapy Protocols adverse effects, Bleomycin administration & dosage, Bleomycin adverse effects, Cyclophosphamide administration & dosage, Cyclophosphamide adverse effects, Disease-Free Survival, Dose-Response Relationship, Drug, Doxorubicin administration & dosage, Doxorubicin adverse effects, Drug Administration Schedule, Female, Follow-Up Studies, Humans, Lymphoma, Large B-Cell, Diffuse diagnosis, Male, Maximum Tolerated Dose, Middle Aged, Prednisolone, Prednisone administration & dosage, Prednisone adverse effects, Prospective Studies, Risk Assessment, Rituximab, Severity of Illness Index, Survival Analysis, Treatment Outcome, Vincristine, Vindesine administration & dosage, Vindesine adverse effects, Young Adult, Antibodies, Monoclonal, Murine-Derived administration & dosage, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Lymphoma, Large B-Cell, Diffuse drug therapy, Lymphoma, Large B-Cell, Diffuse mortality
- Abstract
Background: The outcome of diffuse large B-cell lymphoma has been substantially improved by the addition of the anti-CD20 monoclonal antibody rituximab to chemotherapy regimens. We aimed to assess, in patients aged 18-59 years, the potential survival benefit provided by a dose-intensive immunochemotherapy regimen plus rituximab compared with standard treatment plus rituximab., Methods: We did an open-label randomised trial comparing dose-intensive rituximab, doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone (R-ACVBP) with subsequent consolidation versus standard rituximab, doxorubicin, cyclophosphamide, vincristine, and prednisone (R-CHOP). Random assignment was done with a computer-assisted randomisation-allocation sequence with a block size of four. Patients were aged 18-59 years with untreated diffuse large B-cell lymphoma and an age-adjusted international prognostic index equal to 1. Our primary endpoint was event-free survival. Our analyses of efficacy and safety were of the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00140595., Findings: One patient withdrew consent before treatment and 54 did not complete treatment. After a median follow-up of 44 months, our 3-year estimate of event-free survival was 81% (95% CI 75-86) in the R-ACVBP group and 67% (59-73) in the R-CHOP group (hazard ratio [HR] 0·56, 95% CI 0·38-0·83; p=0·0035). 3-year estimates of progression-free survival (87% [95% CI, 81-91] vs 73% [66-79]; HR 0·48 [0·30-0·76]; p=0·0015) and overall survival (92% [87-95] vs 84% [77-89]; HR 0·44 [0·28-0·81]; p=0·0071) were also increased in the R-ACVBP group. 82 (42%) of 196 patients in the R-ACVBP group experienced a serious adverse event compared with 28 (15%) of 183 in the R-CHOP group. Grade 3-4 haematological toxic effects were more common in the R-ACVBP group, with a higher proportion of patients experiencing a febrile neutropenic episode (38% [75 of 196] vs 9% [16 of 183])., Interpretation: Compared with standard R-CHOP, intensified immunochemotherapy with R-ACVBP significantly improves survival of patients aged 18-59 years with diffuse large B-cell lymphoma with low-intermediate risk according to the International Prognostic Index. Haematological toxic effects of the intensive regimen were raised but manageable., Funding: Groupe d'Etudes des Lymphomes de l'Adulte and Amgen., (Copyright © 2011 Elsevier Ltd. All rights reserved.)
- Published
- 2011
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17. Dacarbazine promotes stromal remodeling and lymphocyte infiltration in cutaneous melanoma lesions.
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Nardin A, Wong WC, Tow C, Molina TJ, Tissier F, Audebourg A, Garcette M, Caignard A, Avril MF, Abastado JP, and Prévost-Blondel A
- Subjects
- Adult, Aged, Aged, 80 and over, Antineoplastic Agents, Alkylating pharmacology, Biopsy, Disease Progression, Extracellular Matrix drug effects, Extracellular Matrix pathology, Female, Gene Expression Regulation, Neoplastic drug effects, Humans, In Vitro Techniques, Kaplan-Meier Estimate, Lymphocytes pathology, Male, Melanoma genetics, Melanoma mortality, Melanoma secondary, Middle Aged, Osteonectin genetics, Osteonectin metabolism, Skin Neoplasms genetics, Skin Neoplasms mortality, Skin Neoplasms pathology, Stromal Cells pathology, Young Adult, Dacarbazine pharmacology, Lymphocytes drug effects, Melanoma drug therapy, Skin Neoplasms drug therapy, Stromal Cells drug effects, Tumor Microenvironment drug effects
- Abstract
Dacarbazine (DTIC) is the standard first-line drug for advanced stage melanoma, but it induces objective clinical responses in only 15% of patients. This study was designed to identify molecular changes specifically induced by treatment in chemo-sensitive lesions. Using global transcriptome analysis and immunohistochemistry, we analyzed cutaneous metastases resected from patients with melanoma before and after DTIC treatment. The treatment induced similar functional changes in different lesions from the same patient. Stromal and immune response-related genes were the most frequently upregulated, particularly in lesions that responded to treatment by stabilizing or regressing. T-cell infiltration and enhanced major histocompatibility complex class II expression were observed in a subset of patients. Stable, chemo-sensitive lesions exhibited activation of genetic programs related to extracellular matrix remodeling, including increased expression of secreted protein acidic and rich in cysteine (SPARC) by tumor cells. These events were associated with local response to treatment and with superior survival in our group of patients. In contrast, SPARC expression was downregulated in lesions resistant to DTIC. Thus, chemotherapy drugs originally selected for their direct cytotoxicity to tumor cells may also influence disease progression by inducing changes in the tumor microenvironment.
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- 2011
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18. Diffuse large B-cell lymphomas with CDKN2A deletion have a distinct gene expression signature and a poor prognosis under R-CHOP treatment: a GELA study.
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Jardin F, Jais JP, Molina TJ, Parmentier F, Picquenot JM, Ruminy P, Tilly H, Bastard C, Salles GA, Feugier P, Thieblemont C, Gisselbrecht C, de Reynies A, Coiffier B, Haioun C, and Leroy K
- Subjects
- Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal administration & dosage, Antibodies, Monoclonal, Murine-Derived, Cyclophosphamide administration & dosage, Doxorubicin administration & dosage, Female, Humans, Lymphoma, Large B-Cell, Diffuse diagnosis, Male, Middle Aged, Prednisone administration & dosage, Prognosis, Proto-Oncogene Proteins c-bcl-2 genetics, Proto-Oncogene Proteins c-myc genetics, Proto-Oncogene Proteins c-rel genetics, Retinoblastoma Protein genetics, Rituximab, Sequence Deletion, Tumor Suppressor Protein p53 genetics, Vincristine administration & dosage, Young Adult, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Cyclin-Dependent Kinase Inhibitor p16 genetics, Gene Expression Profiling, Lymphoma, Large B-Cell, Diffuse drug therapy, Lymphoma, Large B-Cell, Diffuse genetics
- Abstract
Genomic alterations play a crucial role in the development and progression of diffuse large B-cell lymphomas (DLBCLs). We determined gene copy number alterations (GCNAs) of TP53, CDKN2A, CDKN1B, BCL2, MYC, REL, and RB1 with a single polymerase chain reaction (PCR) assay (quantitative multiplex PCR of short fragments [QMPSF]) in a cohort of 114 patients with DLBCL to assess their prognostic value and relationship with the gene expression profile. Losses of TP53 and CDKN2A, observed in 8% and 35% of patients, respectively, were significantly associated with a shorter survival after rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) treatment, independently of the International Prognostic Index and of the cell of origin. Analysis of the 9p21 genomic region indicated that transcripts encoding p14ARF and p16INK4A were both disrupted in most patients with CDKN2A deletion. These patients predominantly had an activated B-cell profile and showed a specific gene expression signature, characterized by dysregulation of the RB/E2F pathway, activation of cellular metabolism, and decreased immune and inflammatory responses. These features may constitute the molecular basis sustaining the unfavorable outcome and chemoresistance of this DLBCL subgroup. Detection of TP53 and CDKN2A loss by QMPSF is a powerful tool that could be used for patient stratification in future clinical trials.
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- 2010
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19. Plasmacytoid dendritic cells accumulate in spleens from chronically HIV-infected patients but barely participate in interferon-alpha expression.
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Nascimbeni M, Perié L, Chorro L, Diocou S, Kreitmann L, Louis S, Garderet L, Fabiani B, Berger A, Schmitz J, Marie JP, Molina TJ, Pacanowski J, Viard JP, Oksenhendler E, Beq S, Abehsira-Amar O, Cheynier R, and Hosmalin A
- Subjects
- Antiretroviral Therapy, Highly Active, CD4-Positive T-Lymphocytes drug effects, CD4-Positive T-Lymphocytes immunology, CD4-Positive T-Lymphocytes virology, Chronic Disease, Endocytosis, Flow Cytometry, Fluorescent Antibody Technique, HIV Infections drug therapy, HIV Infections virology, Humans, Inflammation Mediators metabolism, Interferon-alpha antagonists & inhibitors, Phenotype, Dendritic Cells physiology, HIV Infections immunology, HIV-1 physiology, Interferon-alpha biosynthesis, Spleen immunology
- Abstract
We characterized the localization, phenotype, and some functions of plasmacytoid dendritic cells (pDCs) in the human spleen. pDCs were localized in the marginal zone and the periarteriolar region. Some were also found in the red pulp. pDCs were immature by phenotypic labeling, consistently with their capacity to internalize Dextran in a functional assay. In spleens from HIV-infected patients with thrombocytopenic purpura, these characteristics were unaffected. However, an accumulation of pDCs, but not myeloid dendritic cells (mDCs), was observed in some HIV+ patients, correlating with high proviral loads. Moreover, although undetectable in most HIV- patients, interferon-alpha (IFN-alpha) production was evidenced in situ and by flow cytometry in most HIV+ patients. IFN-alpha was located in the marginal zone. Surprisingly, IFN-alpha colocalized only with few pDCs, but rather with other cells, including T and B lymphocytes, mDCs, and macrophages. Therefore, pDCs accumulated in spleens from HIV+ patients with high proviral loads, but they did not seem to be the main IFN-alpha producers.
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- 2009
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20. Retention of Plasmodium falciparum ring-infected erythrocytes in the slow, open microcirculation of the human spleen.
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Safeukui I, Correas JM, Brousse V, Hirt D, Deplaine G, Mulé S, Lesurtel M, Goasguen N, Sauvanet A, Couvelard A, Kerneis S, Khun H, Vigan-Womas I, Ottone C, Molina TJ, Tréluyer JM, Mercereau-Puijalon O, Milon G, David PH, and Buffet PA
- Subjects
- Animals, Blood Flow Velocity, Humans, In Vitro Techniques, Perfusion, Regional Blood Flow, Spleen parasitology, Erythrocytes parasitology, Microcirculation parasitology, Plasmodium falciparum, Spleen blood supply
- Abstract
The current paradigm in Plasmodium falciparum malaria pathogenesis states that young, ring-infected erythrocytes (rings) circulate in peripheral blood and that mature stages are sequestered in the vasculature, avoiding clearance by the spleen. Through ex vivo perfusion of human spleens, we examined the interaction of this unique blood-filtering organ with P falciparum-infected erythrocytes. As predicted, mature stages were retained. However, more than 50% of rings were also retained and accumulated upstream from endothelial sinus wall slits of the open, slow red pulp microcirculation. Ten percent of rings were retained at each spleen passage, a rate matching the proportion of blood flowing through the slow circulatory compartment established in parallel using spleen contrast-enhanced ultrasonography in healthy volunteers. Rings displayed a mildly but significantly reduced elongation index, consistent with a retention process, due to their altered mechanical properties. This raises the new paradigm of a heterogeneous ring population, the less deformable subset being retained in the spleen, thereby reducing the parasite biomass that will sequester in vital organs, influencing the risk of severe complications, such as cerebral malaria or severe anemia. Cryptic ring retention uncovers a new role for the spleen in the control of parasite density, opening novel intervention opportunities.
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- 2008
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21. Intensive conventional chemotherapy (ACVBP regimen) compared with standard CHOP for poor-prognosis aggressive non-Hodgkin lymphoma.
- Author
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Tilly H, Lepage E, Coiffier B, Blanc M, Herbrecht R, Bosly A, Attal M, Fillet G, Guettier C, Molina TJ, Gisselbrecht C, and Reyes F
- Subjects
- Aged, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Antineoplastic Combined Chemotherapy Protocols adverse effects, Bleomycin administration & dosage, Bleomycin adverse effects, Cyclophosphamide administration & dosage, Cyclophosphamide adverse effects, Disease-Free Survival, Doxorubicin administration & dosage, Doxorubicin adverse effects, Female, Humans, Life Tables, Male, Middle Aged, Prednisone administration & dosage, Prednisone adverse effects, Remission Induction, Survival Analysis, Survival Rate, Vincristine administration & dosage, Vincristine adverse effects, Vindesine administration & dosage, Vindesine adverse effects, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Lymphoma, Non-Hodgkin drug therapy
- Abstract
We conducted a randomized trial to compare the intensive conventional chemotherapy regimen ACVBP (doxorubicin, cyclophosphamide, vindesine, bleomycin, prednisone) with standard CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) in previously untreated patients with poor-risk aggressive lymphoma. Patients aged 61 to 69 years who had aggressive non-Hodgkin lymphoma with at least one prognostic factor of the age-adjusted international prognostic index (IPI) were included. ACVBP consisted of an induction phase of intensified chemotherapy and central nervous system (CNS) prophylaxis followed by a sequential consolidation phase. Of the 708 patients registered for the study, 635 were eligible. The rate of complete response was 58% in the ACVBP group and 56% in the CHOP group (P =.5). Treatment-related death occurred in 13% of the ACVBP group and 7% of the CHOP group (P =.014). At 5 years, the event-free survival was 39% in the ACVBP group and 29% in the CHOP group (P =.005). The overall survival was significantly longer for patients treated with ACVBP, at 5 years it was 46% compared with 38% for patients treated with CHOP (P =.036). CNS progressions or relapses were more frequent in the CHOP group (P =.004). Despite higher toxicity, the ACVBP regimen, used as first-line treatment for patients with poor-risk aggressive lymphoma, is superior to standard CHOP with regard to both event-free survival and overall survival.
- Published
- 2003
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22. Prognostic significance of survivin expression in diffuse large B-cell lymphomas.
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Adida C, Haioun C, Gaulard P, Lepage E, Morel P, Briere J, Dombret H, Reyes F, Diebold J, Gisselbrecht C, Salles G, Altieri DC, and Molina TJ
- Subjects
- Adolescent, Adult, Aged, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Follow-Up Studies, Humans, Immunohistochemistry, Inhibitor of Apoptosis Proteins, Lymphoma, Large B-Cell, Diffuse drug therapy, Lymphoma, Large B-Cell, Diffuse pathology, Middle Aged, Neoplasm Proteins, Prognosis, Randomized Controlled Trials as Topic, Survival Analysis, Survivin, Lymphoma, Large B-Cell, Diffuse metabolism, Microtubule-Associated Proteins, Protein Biosynthesis
- Abstract
Survivin is an inhibitor of apoptosis overexpressed in various human cancers but undetectable in normal differentiated tissues. A potential expression and prognostic significance of survivin was studied in 222 patients with diffuse large B-cell lymphomas (centroblastic, 96%; immunoblastic, 4%). All patients were enrolled between 1987 and 1993 (median follow-up, 7 years) in the LNH87 protocol of the Groupe d'Etudes des Lymphomes de l'Adulte (GELA) and treated either with the reference ACVBP arm (doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone)[AU3A] (n = 79) or other experimental anthracycline-containing regimens (n = 143). The characteristics of these patients were median age of 56 years; serum lactate dehydrogenase (LDH) greater than 1N, 60%; stage III-IV, 55%; performance status, according to the Eastern Cooperative Oncology Group (ECOG) scale, more than 1, 23%; extranodal sites more than 1, 29%; mass more than 10 cm, 44%; bone marrow involvement, 15%. Of the 222 patients studied, 134 (60%) revealed survivin expression in virtually all tumor cells by immunohistochemistry. The overall 5-year survival rate was significantly lower in patients with survivin expression than in those without (40% vs 54%, P =.02). Multivariate analysis incorporating prognostic factors from the International Prognostic Index (IPI) identified survivin expression as an independent predictive parameter on survival (P =.03, relative risk [RR] = 1.6) in addition to LDH (P =.02, RR = 1.6), stage (P =.03, RR = 1.7), and ECOG scale (P =.05, RR = 1.6). A second analysis incorporating IPI as a unique parameter demonstrated that survivin expression (P =.02, RR = 1.6) remained a prognostic factor for survival independently of IPI (P =.001, RR = 1.5). Survivin expression may be considered a new unfavorable prognostic factor of diffuse large B-cell lymphoma. (Blood. 2000;96:1921-1925)
- Published
- 2000
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