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Dreuil-lès-Amiens, France

Gohring G.,Hannover Medical School | Giagounidis A.,Oncology and Clinical Immunology | Busche G.,Hannover Medical School | Hofmann W.,Hannover Medical School | And 4 more authors.
Haematologica | Year: 2011

In patients with low and intermediate risk myelodysplastic syndrome and deletion 5q (del(5q)) treated with lenalidomide, monitoring of cytogenetic response is mandatory, since patients without cytogenetic response have a significantly increased risk of progression. Therefore, we have reviewed cytogenetic data of 302 patients. Patients were analyzed by karyotyping and fluorescence in situ hybridization. In 85 patients, del(5q) was only detected by karyotyping. In 8 patients undergoing karyotypic evolution, the del(5q) and additional chromosomal aberrations were only detected by karyotyping. In 3 patients, del(5q) was only detected by fluorescence in situ hybridization, but not by karyotyping due to a low number of metaphases. Karyotyping was significantly more sensitive than fluorescence in situ hybridization in detecting the del(5q) clone. In conclusion, to optimize therapy control of myelodysplastic syndrome patients with del(5q) treated with lenalidomide and to identify cytogenetic non-response or progression as early as possible, fluorescence in situ hybridization alone is inadequate for evaluation. Karyotyping must be performed to optimally evaluate response. © 2011 Ferrata Storti Foundation. Source

Myelodysplastic syndromes (MDS) are associated with increased bone marrow vascularity and increased levels of various angiogenic factors including Vascular Endothelial Growth Factor (VEGF) which is implicated in the proliferation and survival of leukemic cells. Before the approval of hypomethylating agents in this indication, the GFM conducted a multicenter phase II trial testing the efficacy and tolerance of bevacizumab, a humanized monoclonal antibody against VEGF, in MDS with excess of marrow blasts and its impact on bone marrow angiogenesis. Twenty-one patients were enrolled (16 males and five females) with a median age of 70 years and 19 were evaluable for haematological response after treatment (5 mg/kg IV every 2 weeks for 12 weeks). WHO diagnosis at baseline was RAEB-1 (38%) and RAEB-2 (62%). Treatment was well tolerated and was associated with significant decrease of VEGF plasma level [median (low quartile-high quartile)] from 65.5 pg/ml [LQ (low-quartile)-HQ (high quartile), 35.3-87.3 to 30.4 pg/ml (LQ-HQ, 22.5-34.0 pg/ml)] (p < 0.01) and reduction of bone marrow angiogenesis from a median of 20 vessels/mm(3) (LQ-HQ, 16.5-33 vessels/mm(3)) to 15.5 vessels/mm(3) (LQ-HQ, 10-23.2 vessels/mm(3)) (p = 0.03). On the other hand, only one patient had a significant haematological response with achievement of RBC transfusion independence. Thus, although bevacizumab had a significant impact on VEGF levels and angiogenesis in our patients, very few responses were seen when this drug was used as single agent. Given its good tolerability profile, however, combination of bevacizumab with other drugs, especially hypomethylating agents, could be considered in MDS. Source

Fardet L.,Service de Medecine Interne | Lambotte O.,Service de Medecine Interne | Meynard J.-L.,Service de Maladies Infectieuses | Kamouh W.,Service de Medecine Interne | And 8 more authors.
AIDS | Year: 2010

OBJECTIVE: To describe features of reactive haemophagocytic syndrome (RHS) in HIV-1-infected adult patients. To compare characteristics of patients with malignancy-associated RHS and infection-associated RHS. DESIGN AND SETTING: Retrospective study in three departments of Infectious Diseases/Internal Medicine at three French tertiary centres. PATIENTS AND METHODS: Medical charts of HIV-1-infected adult patients and RHS seen between January 2006 and December 2007 were reviewed. Demographic, clinical and laboratory data obtained at the time of RHS episode were compared between patients with malignancy-associated RHS and infection-associated RHS using non-parametric tests. The overall survival was assessed using the Kaplan-Meier method. RESULTS: Fifty-eight HIV-1-infected patients were diagnosed with RHS [certain RHS n = 43, possible RHS n = 15, median (range) age 42 (23-85) years, men 76%]. At time of RHS, the median duration of HIV infection was 4 (0-22) years and 57% received HAART. The median CD4 lymphocyte count was 91 (2-387)/μl and 35% of patients had a plasma HIV-1 RNA less than 50 copies/ml. Underlying haemopathy/malignancy (Hodgkin lymphoma n = 10) or infection (tuberculosis n = 9, cytomegalovirus infection n = 5) were evidenced for 31 and 23 patients, respectively. Patients with haemopathy/malignancy-associated RHS presented more frequently with splenomegaly (97 vs. 70%, P < 0.01), lower aspartate aminotransferase (36 vs. 84 UI/l, P < 0.01) and lactate dehydrogenase (530 vs. 911 UI/l, P < 0.01) levels and CD8 cell count (234 vs. 588/μl, P < 0.01). Eighteen (31%) patients died. The overall survival was not statistically different between the two groups (P = 0.68). CONCLUSION: In the HAART era, RHS is frequently associated with underlying haemopathy/malignancy, especially Hodgkin lymphoma. The prognosis remains poor but seems, however, better than in the pre-HAART era. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins. Source

Dohner H.,University of Ulm | Estey E.H.,Seattle Cancer Center Alliance | Amadori S.,University of Rome Tor Vergata | Appelbaum F.R.,Fred Hutchinson Cancer Research Center | And 14 more authors.
Blood | Year: 2010

In 2003, an international working group last reported on recommendations for diagnosis, response assessment, and treatment outcomes in acute myeloid leukemia (AML). Since that time, considerable progress has been made in elucidating the molecular pathogenesis of the disease that has resulted in the identification of new diagnostic and prognostic markers. Furthermore, therapies are now being developed that target diseaseassociated molecular defects. Recent developments prompted an international expert panel to provide updated evidenceand expert opinion-based recommendations for the diagnosis and management of AML, that contain both minimal requirements for general practice as well as standards for clinical trials. A new standardized reporting system for correlation of cytogenetic and molecular genetic data with clinical data is proposed. © 2010 by The American Society of Hematology. Source

Ades L.,Service dHematologie Clinique | Santini V.,University of Florence
Bailliere's Best Practice and Research in Clinical Haematology | Year: 2013

Until recently, the treatment of higher risk myelodysplastic syndrome was based on [1] Intensive chemotherapy using anthracycline-AraC combinations, leading to a lower complete remission rates and a shorter CR duration compared with de novo AML [2], low dose chemotherapy with limited CR rate mainly restricted to patients with normal karyotype. Azacitidine was the first drug to significantly improve survival in higher risk MDS, although it is not curative. Thus, the survival improvement obtained with azacitidine must be the starting point for combination studies, and for utilization of this drug in other situations (before allo SCT, or after chemotherapy or allo SCT as maintenance treatment). © 2013 Elsevier Ltd. All rights reserved. Source

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