The online version of this article has a Supplementary Appendix. BackgroundThe prognostic value of cytogenetic findings in chronic myelomonocytic leukemia is unclear. Our purpose was to evaluate the independent prognostic impact of cytogenetic abnormalities in a large series of patients with chronic myelomonocytic leukemia included in the database of the Spanish Registry of Myelodysplastic Syndromes. Design and MethodsWe studied 414 patients with chronic myelomonocytic leukemia according to WHO criteria and with a successful conventional cytogenetic analysis at diagnosis. Different patient and disease characteristics were examined by univariate and multivariate methods to establish their relationship with overall survival and evolution to acute myeloid leukemia. ResultsPatients with abnormal karyotype (110 patients, 27%) had poorer overall survival (P=0.001) and higher risk of acute myeloid leukemia evolution (P=0.010). Based on outcome analysis, three cytogenetic risk categories were identified: low risk (normal karyotype or loss of Y chromosome as a single anomaly), high risk (presence of trisomy 8 or abnormalities of chromosome 7, or complex karyotype), and intermediate risk (all other abnormalities). Overall survival at five years for patients in the low, intermediate, and high risk cytogenetic categories was 35%, 26%, and 4%, respectively (P<0.001). Multivariate analysis confirmed that this new CMMLspecific cytogenetic risk stratification was an independent prognostic variable for overall survival (P=0.001). Additionally, patients belonging to the high-risk cytogenetic category also had a higher risk of acute myeloid leukemia evolution on univariate (P=0.001) but not multivariate analysis. ConclusionsCytogenetic findings have a strong prognostic impact in patients with chronic myelomonocytic leukemia.Key words: chronic myelomonocytic leukemia, CMML, cytogenetic. leukemia. Haematologica 2011;96(3):375-383. doi:10.3324/haematol.2010 This is an open-access paper. Citation: Such E, Cervera J, Costa D, Solé F, Vallespí T, Luño E, Collado R, Calasanz MJ, Hernández-Rivas JM, Cigudosa JC, Nomdedeu B, Mallo M, Carbonell F, Bueno J, Ardanaz MT, Ramos F, Tormo M, Sancho-Tello R, del Cañizo C, Gómez V, Marco V, Xicoy B, Bonanad S, Pedro C, Bernal T, and Sanz GF. Cytogenetic risk stratification in chronic myelomonocytic Cytogenetic risk stratification in chronic myelomonocytic leukemia

2016) Complex karyotypes and KRAS and POT1 mutations impact outcome in CLL after chlorambucilbased chemotherapy or chemoimmunotherapy. Blood, 128, 395-404.

This cooperative study assessed prognostic factors for overall survival (OS) and risk of transformation to acute myeloid leukemia (AML) in 541 patients with de novo myelodysplastic syndrome (MDS) and deletion 5q. Additional chromosomal abnormalities were strongly related to different patients' characteristics. In multivariate analysis, the most important predictors of both OS and AML transformation risk were number of chromosomal abnormalities (Po0.001 for both outcomes), platelet count (Po0.001 and P ¼ 0.001, respectively) and proportion of bone marrow blasts (Po0.001 and P ¼ 0.016, respectively). The number of chromosomal abnormalities defined three risk categories for AML transformation (del(5q), del(5q) þ 1 and del(5q) þ X2 abnormalities) and two for OS (one group: del(5q) and del(5q) þ 1; and del(5q) þ X2 abnormalities, as the other one); with a median survival time of 58.0 and 6.8 months, respectively. Platelet count (P ¼ 0.001) and age (P ¼ 0.034) predicted OS in patients with '5qÀsyndrome'. This study demonstrates the importance of additional chromosomal abnormalities in MDS patients with deletion 5q, challenges the current '5qÀsyndrome' definition and constitutes a useful reference series to properly analyze the results of clinical trials in these patients.

After accounting for karyotype complexity, MK was not associated with OS or evolution to AML. In conclusion, these results demonstrate that the prognostic value of MK in MDS is not independent and is mainly the result of its strong association with number of chromosomal abnormalities.

Vibriosis due to Vibrio vulnificus serovar E (biotype 2) is one of the main causes of mortality in European eels cultured in Europe. The main objective of this study was to develop a vaccine and a vaccination procedure against this pathogen. With this aim, we tested several vaccine formulations (inactivated whole-cells with and without toxoids -inactivated extracellular products -from capsulated and uncapsulated strains, attenuated live vaccines and purified lipopolysaccharide [LPS]) on eels maintained under controlled laboratory conditions using different delivery routes (injection and immersion). To study the immune response we estimated antibody titers and bactericidal/bacteriostatic activity in mucus and serum. To evaluate protection, we calculated the relative percent survival (RPS) after intraperitoneal (i.p.) injection and bath challenge of the pathogen. The overall results indicate that: (1) capsular antigens seem to be essential for protective immunization; (2) vaccines confer the highest protection when administered by i.p. injection; (3) booster is needed to achieve good protection by immersion; (4) enriching the vaccine with toxoids enhances protection to optimal levels (RPS values around 70 to 100%, depending on the delivery route); and (5) the protective effect in serum and mucus depends on the route of administration and seems to be related to the production of specific antibodies. KEY WORDS: Vibrio vulnificus serovar E · Vibrio vulnificus biotype 2 · Eel vaccines · Vibrio vaccines · Vaccination by injection · Vaccination by prolonged immersion Resale or republication not permitted without written consent of the publisherDis Aquat Org 43: [91][92][93][94][95][96][97][98][99][100][101] 2000 Vibrio vulnificus serovar E is an opportunistic human pathogen (Amaro & Biosca 1996) which is able to survive and spread infection through water (Amaro et al. 1995).To make eel culture profitable, in both brackish and fresh water, alternative strategies are needed to solve the problem, and should focus mainly on preventative measures. The use of vaccines in aquaculture has been shown to successfully protect fish against bacterial diseases, such as vibriosis (caused by Listonella anguillarum [formerly Vibrio anguillarum] and V. ordalii ), edwardsiellosis, furunculosis, streptococcosis and pasteurellosis (Song et al. 1982, Austin 1983, Larsen 1988, Smith 1988, Dec et al. 1990, Roogers & Xu 1992, Magariños et al. 1994, Quentel & Ogier de Baulny 1995, Toranzo et al. 1995, Romalde et al. 1996, Gravningen et al. 1998. In particular, the success achieved in immunization against other vibrioses (Smith 1988) suggests that the best solution would be an effective vaccine against V. vulnificus. Although numerous vaccines against other vibrioses have been developed and licensed to date, no vaccine against V. vulnificus serovar E is available at present. The main objective of this study was to develop a vaccine and a vaccination procedure against this pathogen. With this aim, we tested several vaccine formulatio...