26 research outputs found

    Spontaneous remission of fully symptomatic visceral leishmaniasis

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    International audienceBackground: Visceral leishmaniasis (VL), i.e., infection with Leishmania sp. associated with high fever, weight loss, massive splenomegaly and markedly altered laboratory parameters, is generally fatal if untreated. The possibility of transient spontaneous remission of fully symptomatic visceral leishmaniasis (VL) has been mentioned but, to our knowledge) has never been documented. Case presentation: We report the first documented history of a patient with overt, confirmed VL experiencing a complete remission in the absence of any anti-leishmanial therapy. The diagnosis of VL at the time of the self-resolving episode was strongly suspected based on clinical presentation and presence of antileishmanial antibody, then unequivocally confirmed years later by the presence of an amastigote on a stored smear and the positive quantitative PCR with Leishmania-specific primers from the material scraped from this same slide Conclusion: This report demonstrates that complete spontaneous remission may occur in patients with overt, fully symptomatic VL. VL should therefore be considered in cases of self-resolving or relapsing episodes of fever of unknown origin. Confirmation should be based on both serological tests and specific PCR on a blood sample

    Long-term follow-up and second malignancies in 487 patients with hairy cell leukaemia

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    International audienceA large, multicentre, retrospective survey of patients with hairy cell leukaemia (HCL) was conducted in France to determine the frequency of second malignancies and to analyse the long-term effects of the established purine nucleoside analogues (PNAs), cladribine and pentostatin. The survey retrospectively reviewed the medical history of patients and their immediate family, clinical and biological presentation at the time of HCL diagnosis, treatment choice, response to treatment, time to relapse and cause of death. Data were collected for 487 patients with HCL. Of the patients included in the survey, 18% (88/487) had a familial history of cancers, 8% (41/487) presented with malignancies before HCL diagnosis and 10% (48/487) developed second malignancies after HCL was diagnosed. An excess incidence of second malignancies was observed, with a standardized incidence ratio (SIR) of 1·86 (95% confidence interval (CI): 1·34-2·51), with no significant difference between PNAs. For second haematological malignancies alone, the SIR was markedly increased at 5·32 (95% CI: 2·90-8·92). This study highlights the high frequency of cancers in HCL patients and their family members. The frequency of second malignancies is notably increased, particularly for haematological malignancies. The respective role of pentostatin and cladribine in the development of second malignancies is debatable

    Analysis of the ten-eleven translocation 2 (TET2) gene in familial myeloproliferative neoplasms.

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    International audienceThe JAK2(V617F) mutation does not elucidate the phenotypic variability observed in myeloproliferative neoplasm (MPN) families. A putative tumor suppressor gene, TET2, was recently implicated in MPN and myelodysplastic syndromes through the identification of acquired mutations affecting hematopoietic stem cells. The present study analyzed the TET2 gene in 61 MPN cases from 42 families. Fifteen distinct mutations were identified in 12 (20%) JAK2(V617F)-positive or -negative patients. In a patient with 2 TET2 mutations, the analysis of 5 blood samples at different phases of her disease showed the sequential occurrence of JAK2(V617F) and TET2 mutations concomitantly to the disease evolution. Analysis of familial segregation confirmed that TET2 mutations were not inherited but somatically acquired. TET2 mutations were mainly observed (10 of 12) in patients with primary myelofibrosis or patients with polycythemia vera or essential thrombocythemia who secondarily evolved toward myelofibrosis or acute myeloid leukemia

    HIV therapeutic vaccine enhances non-exhausted CD4(+) T cells in a randomised phase 2 trial

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    VAC-3S is a therapeutic vaccine comprising a highly conserved HIV-gp41 motif coupled with the CRM197 carrier protein. High levels of anti-3S antibodies (Abs) have been associated with improved protection of CD4(+) T-cell survival. A previous phase 1 study demonstrated the safety of VAC-3S. This multicentre, randomised, double-blind, placebo-controlled phase 2 clinical trial enroled between January 2014 and March 2015 HIV-1-infected patients under ART with plasma HIV RNA levels below 50 copies/mL and CD4 counts between 200 and 500 cells/mu L. Participants were immunised with 16, 32, or 64 mu g of VAC-3S, and compared to placebo. The primary outcome was immunogenicity assessed by changes from baseline of anti-3S Abs levels at week 12. Secondary outcomes included adverse events and the course of plasma HIV RNA level, CD4 count, CD4/CD8 ratio, inflammation and immune checkpoints from week 0 to week 48. Vaccination was well tolerated with no serious adverse events and induced a significant increase in anti-3S Ab response in vaccinated patients (p < 0.0001), compared to placebo. In high responders, the robust increased of CD4 count was associated with a significant and sustained reduction of PD-1 expression on CD4(+) T cells through week 48 (variance p = 0.0017). PD-1 expression was correlated with level of anti-3S Abs (p = 0.0092, r = -0.68) and expression of NKp44L (p < 0.0001; r = 0.54) in CD4(+) T cells. Our findings regarding the increase of non-exhausted CD4(+) T cells have potentially important application in personalised HIV vaccination for HIV-infected patients with high level of PD-1 to improve their T-cell immune function
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