46 research outputs found
Detection of t(11;14) using interphase molecular cytogenetics in mantle cell lymphoma and atypical chronic lymphocytic leukemia
The chromosomal translocation t(11;14)(q13;q32) fuses the IGH and CCND1 genes and leads to cyclin D1 overexpression. This genetic abnormality is the hallmark of mantle cell lymphoma (MCL), but is also found in some cases of atypical chronic lymphocytic leukemia (CLL), characterized by a poor outcome. For an unequivocal assessment of this specific chromosomal rearrangement on interphase cells, we developed a set of probes for fluorescence in situ hybridization (FISH). Northern blotting was performed for analysis of the cyclin D1 expression in 18 patients. Thirty-eight patients, with either a typical MCL leukemic phase (17 patients) or atypical CLL with an MCL-type immunophenotype, i.e., CD19+, CD5+, CD23(-/low), CD79b/sIgM(D)++, and FMC7+ (21 patients), were analyzed by dual-color interphase FISH. We selected an IGH-specific BAC probe (covering the JH and first constant regions) and a commercially available CCND1 probe. An IGH-CCND1 fusion was detected in 28 of the 38 patients (17 typical MCL and 11 cases with CLL). Cyclin D1 was not overexpressed in two patients with typical MCL and an IGH- CCND1 fusion. In view of the poor prognosis associated with MCL and t(11;14)- positive CLL, we conclude that this set of probes is a valuable and reliable tool for a rapid diagnosis of these entities
Long-term outcomes after reduced-intensity conditioning allogeneic stem cell transplantation for low-grade lymphoma: a survey by the French Society of Bone Marrow Graft Transplantation and Cellular Therapy (SFGM-TC).
International audienceBACKGROUND AND OBJECTIVES: High-dose chemotherapy with allogeneic stem cell transplantation (SCT) has proven to be a successful treatment for low-grade lymphoma (LGL), but is associated with considerable transplant-related mortality (TRM). In an effort to reduce toxic mortality while maintaining the graft-versus-leukemia effect, allogeneic SCT has been combined with a reduced-intensity conditioning (RIC) regimen. The aim of this study was to determine the outcome of patients with LGL treated with RIC allogeneic SCT. DESIGN AND METHODS: This retrospective multicenter study included 73 patients with relapsed or refractory LGL allografted after a RIC regimen between 1998 and 2005 whose data were recorded in a French registry. RESULTS: Patients received a median of three lines of therapy prior to RIC allogeneic SCT. The most widely used conditioning regimens were fludarabine + busulfan + antithymocyte globulin (n=43) and fludarabine + total body irradiation (n=21). Prior to allografting, patients were in complete response (CR; n=21), partial response (PR; n=33) or had chemoresistant disease (n=19). The median follow-up was 37 months (range, 16 to 77 months). In patients in CR, PR and chemoresistant disease, the 3-year overall survival rates were 66%, 64% and 32%, respectively, while the 3-year event-free survival rates were 66%, 52% and 32%, respectively. The 3-year cumulative incidences of TRM were 32%, 28% and 63%, respectively. The incidence of relapse was 9.6%. INTERPRETATION AND CONCLUSIONS: Although associated with significant TRM, RIC allogeneic SCT in advanced chemosensitive disease leads to long-term survival
STAT5-and hypoxia-dependent upregulation of AXL
Internal tandem duplication in Fms-like tyrosine kinase 3 (FLT3-ITD) is the most frequent mutation observed in acute myeloid leukemia (AML) and correlates with poor prognosis. FLT3 tyrosine kinase inhibitors are promising for targeted therapy. Here, we investigated mechanisms dampening the response to the FLT3 inhibitor quizartinib, which is specific to the hematopoietic niche. Using AML primary samples and cell lines, we demonstrate that convergent signals from the hematopoietic microenvironment drive FLT3-ITD cell resistance to quizartinib through the expression and activation of the tyrosine kinase receptor AXL. Indeed, cytokines sustained phosphorylation of the transcription factor STAT5 in quizartinib-treated cells, which enhanced AXL expression by direct binding of a conserved motif in its genomic sequence. Likewise, hypoxia, another well-known hematopoietic niche hallmark, also enhanced AXL expression. Finally, in a xenograft mouse model, inhibition of AXL significantly increased the response of FLT3-ITD cells to quizartinib exclusively within a bone marrow environment. These data highlight a new bypass mechanism specific to the hematopoietic niche that hampers the response to quizartinib through combined upregulation of AXL activity. Targeting this signaling offers the prospect of a new therapy to eradicate resistant FLT3-ITD leukemic cells hidden within their specific microenvironment, thereby preventing relapses from FLT3-ITD clones
Comparison of matched sibling donors versus unrelated donors in allogeneic stem cell transplantation for primary refractory acute myeloid leukemia: a study on behalf of the Acute Leukemia Working Party of the EBMT
L'asparaginase dans le traitement de la leucémie aiguë lymphoblastique de l'enfant
La Leucémie aiguë lymphoblastique représente 30% des cancers de l'enfant. L'asparaginase, découverte en 1961, a été intégrée dans les protocoles de traitement de cette maladie et a permis d'augmenter considérablement les taux de survie. Malgré son mode d'action spécifique, la premiÚre forme d'asparaginase, issue d'Escherichia coli, a engendré des effets secondaires. C'est pourquoi les chercheurs ont développé 2 autres formes : l'une issue d'une autre bactérie, Erwinia carotovora, l'autre une forme chimiquement modifiée de la forme native, la pegaspargase. De nombreuses études ont été et sont encore menées afin de trouver les meilleurs protocoles pour optimiser l'efficacité et diminuer les toxicités des 3 formes mais aussi pour déterminer la forme la plus appropriée à utiliser.NANTES-BU Médecine pharmacie (441092101) / SudocSudocFranceF
AUTOGREFFE DANS LA MALADIE DE HODGKIN (EXPERIENCE MONOCENTRIQUE SUR 15 ANS (DES HEMATOLOGIE CLINIQUE))
NANTES-BU MĂ©decine pharmacie (441092101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF
Place de l'allogreffe de cellules souches hématopoïÚtiques dans le traitement du myélome multiple (l'expérience nantaise à propos de 23 cas)
Nous avons Ă©tudiĂ© l'ensemble des allogreffes rĂ©alisĂ©es Ă Nantes pour myĂ©lome multiple entre mars 1988 et octobre 2000 (n=23) et comparĂ© cette sĂ©rie rĂ©trospective Ă une cohorte de patients autogreffĂ©s Ă Nantes durant la mĂȘme pĂ©riode (n=55). La date du dernier suivi a Ă©tĂ© fixĂ© au 30 juin 2001. Notre Ă©tude montre l'intĂ©rĂȘt de proposer une allogreffe Ă un patient jeune atteint de myĂ©lome multiple aprĂšs le minimum de traitement (<=<2 lignes, p=0,009) et avant mĂȘme la rĂ©alisation d'une autogreffe (p=0,009 La survie globale est comparable aprĂšs allogreffe (mĂ©diane 20 mois) et autogreffe (mĂ©diane 27 mois) (p=0,5) mais la survie sans rechute est significativement prolongĂ©e aprĂšs allogreffe pour les patients en rĂ©ponse (mĂ©diane non atteinte versus 5 mois, p=0,006). La mortalitĂ© liĂ©e au traitement demeure le problĂšme principal de l'allogreffe, impliquant le dĂ©veloppement et l'Ă©mergence de nouvelles approches thĂ©rapeutiques, ainsi que de modalitĂ©s visant Ă rĂ©duire la toxicitĂ© de l'allogreffe, comme la rĂ©alisation de greffes Ă conditionnement attĂ©nuĂ©, dont les rĂ©sultats prĂ©liminaires semblent prometteurs.NANTES-BU MĂ©decine pharmacie (441092101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF
Etude des facteurs de risque de GVH chronique aprÚs allogreffe de cellules souches hématopoïétiques à conditionnement atténué
BORDEAUX2-BU Santé (330632101) / SudocSudocFranceF
NEPHROTOXICITE DES TRAITEMENTS PREVENTIFS ET/OU CURATIFS DES COMPLICATIONS DE L'ALLOGREFFE DE MOELLE OSSEUSE ET INTERET DE L'UTILISATION DES FORMES LIPOSOMALES (EVALUATION PROSPECTIVE CHEZ 31 PATIENTS NANTAIS)
NANTES-BU MĂ©decine pharmacie (441092101) / SudocSudocFranceF
JACIE fĂȘte son dixiĂšme anniversaire
JACIE (Joint accreditation committee for ISCT Europe and EBMT) est un systĂšme de management de la qualitĂ© Ă©laborĂ© Ă lâĂ©chelle europĂ©enne sous lâĂ©gide de deux sociĂ©tĂ©s savantes. LâoriginalitĂ© de cette dĂ©marche est quâelle sâapplique Ă lâensemble des principaux acteurs : services cliniques et plateaux hospitaliers mĂ©dicotechniques et biologiques (responsables du prĂ©lĂšvement de cellules et de lâingĂ©nierie cellulaire) contribuant Ă une procĂ©dure thĂ©rapeutique complexe, la greffe de cellules hĂ©matopoĂŻĂ©tiques. LedĂ©ploiement de JACIE a dĂ©butĂ© il y a dix ans. Une analyse rĂ©trospective rĂ©cente du registre europĂ©en des greffes de cellules hĂ©matopoĂŻĂ©tiques autologues et allogĂ©niques montre que lâun des facteurs influençant positivement la survie globale des patients allogreffĂ©s est le fait de recevoir lâallogreffe dans le cadre dâun programme de soins accrĂ©ditĂ© JACIE. Il sâagit dâune des premiĂšres dĂ©monstrations, Ă large Ă©chelle, de lâutilitĂ© dâune dĂ©marche de management de la qualitĂ© pour amĂ©liorer le taux de succĂšs dâune procĂ©dure thĂ©rapeutique complexe