In an intention-to-treat analysis, the post-ASCT CR rate was higher with VTD than with TD (46% vs 24%, P ‫؍‬ .004) or with VBMCP/ VBAD/B (46% vs 38%, P ‫؍‬ .1). Patients with high-risk cytogenetics had a shorter PFS and overall survival in the overall series and in all treatment groups. In conclusion, VTD resulted in a higher preand posttransplantation CR rate and in a significantly longer PFS although it was not able to overcome the poor prognosis of high-risk cytogenetics. Our results support the use of VTD as a highly effective induction regimen prior to ASCT. The study was registered with http://www.clinicaltrials.gov (NCT00461747) and Eudra CT (no.

We have analyzed the applicability, sensitivity and prognostic value of allele-specific oligonucleotide real-time quantitative PCR (ASO RQ-PCR) as a method for minimal residual disease (MRD) assessment in patients with multiple myeloma (MM), comparing the results with those of multiparameter flow cytometry (MFC). A total of 170 patients enrolled in three consecutive Spanish trials achieving at least partial response after treatment were included. Lack of clonality detection (n=31), unsuccessful sequencing (n=17) and suboptimal ASO performance (n=51) limited the applicability of PCR to 42% of cases. MRD was finally investigated in 103 patients (including 32 previously studied) with persistent disease identified by PCR and MFC in 54% and 46% of cases, respectively. A significant correlation in MRD quantitation by both the techniques was noted (r=0.881, P<0.001), being reflective of treatment intensity. Patients with <10(-4) residual tumor cells showed longer progression-free survival (PFS) compared with the rest (not reached (NR) vs 31 months, P=0.002), with similar results observed with MFC. Among complete responders (n=62), PCR discriminated two risk groups with different PFS (49 vs 26 months, P=0.001) and overall survival (NR vs 60 months, P=0.008). Thus, although less applicable than MFC, ASO RQ-PCR is a powerful technique to assess treatment efficacy and risk stratification in MM.

The study of host-parasite relationships involving vector-borne parasites requires understanding interactions between parasites and vectors. The capacity of haemosporidians to infect insects has clear evolutionary consequences for the transmission of diseases. Here, we investigated (i) the associations between blood parasites, biting midges and birds and (ii) the potential specificity between biting midge and haemosporidian haplotypes. A total of 629 parous biting midges Culicoides and 224 wild birds (belonging to seven species) from a locality of central Spain were individually examined for the presence of Haemoproteus and Plasmodium parasites by sequencing a fragment of cytochrome B. Biting midges were identified morphologically and characterized on the basis of a fragment of the cytochrome c oxidase (COI) gene. Overall, 12 Haemoproteus and three Plasmodium haplotypes were isolated and sequenced. Among them, 10 haplotypes were exclusively isolated from biting midges, three haplotypes only from birds and two haplotypes from both biting midges and birds. Biting midge haplotypes showed both specific and generalist relationships with Haemoproteus haplotypes but only generalist relationships with Plasmodium haplotypes. Several C. festivipennis and C. kibunesis haplotypes established significant coevolutionary links with Haemoproteus haplotypes. These results shed light on the specificity of interactions between vectors and blood parasites.

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IntroductionWhile blood parasites are common in many birds in the wild, some groups seem to be much less affected. Seabirds, in particular, have often been reported free from blood parasites, even in the presence of potential vectors.ResultsFrom a literature review of hemosporidian prevalence in seabirds, we collated a dataset of 60 species, in which at least 15 individuals had been examined. These data were included in phylogenetically controlled statistical analyses of hemosporidian prevalence in relation to ecological and life-history parameters. Haemoproteus parasites were common in frigatebirds and gulls, while Hepatozoon occurred in albatrosses and storm petrels, and Plasmodium mainly in penguins. The prevalence of Haemoproteus showed a geographical signal, being lower in species with distribution towards polar environments. Interspecific differences in Plasmodium prevalence were explained by variables that relate to the exposure to parasites, suggesting that prevalence is higher in burrow nesters with long fledgling periods. Measures of Plasmodium, but not Haemoproteus prevalences were influenced by the method, with PCR-based data resulting in higher prevalence estimates.ConclusionsOur analyses suggest that, as in other avian taxa, phylogenetic, ecological and life-history parameters determine the prevalence of hemosporidian parasites in seabirds. We discuss how these relationships should be further explored in future studies.