Place de la mutation JAK2 V617F dans le diagnostic de syndrome myéloprolifératif chez les patients de syndrome Budd-Chiari et de thrombose portale

Dans la littérature, 50% des syndromes de Budd-Chiari (SBC) et 30% des thromboses de la veine porte (TVP) seraient secondaires à un syndrome myéloprolifératif (SMP). Le diagnostic de SMP est difficile, basé sur la biopsie ostéo-médullaire (BOM) et la culture des progéniteurs érythroïdes médullaires, examens invasifs. Cette étude multicentrique de 104 SBC et 137 TVP a évalué l apport diagnostique et pronostique de la recherche de la mutation V617F de la tyrosine kinase JAK2, récemment découverte dans les SMP. Selon les résultats de BOM et de culture, 29% des patients avaient un SMP, 41% non et 31% des résultats discordants. La mutation JAK2 a été recherchée par RT-PCR chez tous les patients. JAK2 V617F a été trouvée chez 39% des patients, 45,2% des SBC et 34,3% des TVP. Elle était corrélée à la présence d un SMP sur la BOM et à la présence de colonies érythroblastiques spontanées (p<0.0001) et était présente chez 83.8% des BOM+, 18.5% des BOM- et 58% des cas discordants entre la BOM et la culture des progéniteurs. Comparée avec la BOM, la mutation de JAK2 permet d augmenter la fréquence de diagnostic de SMP de 13% pour toute la cohorte, de 18% dans les SBC et de 9% dans les TVP. Le statut mutationnel de JAK2 n avait pas d influence sur les survies globales et sans évènements (SSE), dans les groupes de SBC et de TVP. Cependant, dans les SBC, les scores pronostiques indiquaient une atteinte hépatique plus sévère en cas de mutation de JAK2. De même, la SSE des SBC avec un SMP sous-jacent était significativement plus courte. Nous proposons d intégrer la recherche de la mutation de JAK2 comme premier test diagnostique de SMP dans le contexte des thromboses splanchniques.PARIS6-Bibl.Pitié-Salpêtrie (751132101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Evolving characteristics and outcome of secondary acute promyelocytic leukemia (APL): A prospective analysis by the French-Belgian-Swiss APL group.

BACKGROUND: Reports of patients with secondary acute promyelocytic leukemia (APL) have increased in recent years, particularly for those who received treatment with mitoxantrone, and retrospective studies have suggested that their characteristics and outcomes were similar to those of patients with de novo APL. METHODS: The authors investigated patients with de novo and secondary APL who were included in the ongoing APL-2006 trial. Patients with secondary APL who were included in that trial also were compared with a previous retrospective cohort of patients with secondary APL. RESULTS: In the APL-2006 trial, 42 of 280 patients (15%) had secondary APL. Compared with the retrospective cohort, patients with secondary APL in the APL-2006 trial had a lower incidence of prior breast carcinoma (35.7% vs 57%; P = .03) and a higher incidence of prior prostate carcinoma (26.2% vs 4.7%; P &lt; .001). Treatment of the primary tumor in the APL-2006 trial less frequently included combined radiochemotherapy (28.6% vs 47.2%; P = .044) and no mitoxantrone (0% vs 46.7%; P = .016) but more frequently included anthracyclines (53.3% vs 38.3%; P = .015). In the APL-2006 trial, patients who had secondary APL, compared with those who had de novo APL, were older (mean, 60.2 years vs 48.7 years, respectively; P &lt; .0001) but had a similar complete response rate (97.6% vs 90.3%, respectively), cumulative incidence of relapse (0% vs 1.8%, respectively), and overall survival (92.3% vs 90.9%, respectively) at 18 months. CONCLUSIONS: Although the incidence of secondary APL appears to be stable over time, evolving strategies for the treatment of primary cancers have reduced its occurrence among breast cancer patients but have increased its incidence among patients with prostate cancer. The current results confirm prospectively that patients with secondary APL have characteristics and outcomes similar to those of patients with de novo APL. Cancer 2015;121:2393-2399. © 2015 American Cancer Society

Carfilzomib Weekly Plus Melphalan and Prednisone in Newly Diagnosed Elderly Multiple Myeloma (IFM 2012-03) / 57th Annual Meeting of the American-Society-of-Hematology - Orlando, FL

WOS:000368020103223International audienceConference: 57th Annual Meeting of the American-Society-of-Hematology - Orlando, FL - DEC 05-08, 201

The impact of JAK2 and MPL mutations on diagnosis and prognosis of splanchnic vein thrombosis: A report on 241 cases

Myeloproliferative diseases (MPDs) represent the commonest cause of splanchnic vein thrombosis (SVT), including Budd- Chiari syndrome (BCS) and portal vein thrombosis (PVT), but their diagnosis is hampered by changes secondary to portal hypertension, while their influence in the outcome of SVT remains unclear. We assessed the diagnostic and prognostic value of JAK2 and MPL515 mutations in 241 SVT patients (104 BCS, 137 PVT). JAK2V617F was found in 45% of BCS and 34% of PVT, while JAK2 exon 12 and MPL515 mutations were not detected. JAK2V617F was found in 96.5% of patients with bone marrow (BM) changes specific for MPD and endogenous erythoid colonies, but also in 58% of those with only one feature and in 7% of those with neither feature. Stratifying MPD diagnosis first on JAK2V617F detection would have avoided BM investigations in 40% of the patients. In BCS, presence of MPD carried significantly poorer baseline prognostic features, required hepatic decompression procedures earlier, but had no impact on 5-year survival. Our results suggest that JAK2V617F testing should replace BM investigations as initial test for MPD in patients with SVT. Underlying MPD is associated with severe forms of BCS, but current therapy appears to offset deleterious effects of MPD on the medium-term outcome