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BK virus (BKV) reactivation has been increasingly associated with the occurrence of late-onset hemorrhagic cystitis (HC) after allogeneic hematopoietic SCT (allo-HSCT) resulting in morbidity and sometimes mortality. We investigated the incidence, risk factors and outcome of BKV-HC in 323 consecutive adult patients undergoing allo-HSCT over a 5-year period. BK viremia values for HC staging were evaluated, as well as the medico-economic impact of the complication. Forty-three patients developed BKV-HC. In univariate analysis, young age ( P =0.028), unrelated donor ( P =0.0178), stem cell source ( P =0.0001), HLA mismatching ( P =0.0022) and BU in conditioning regimen ( P =0.01) were associated with a higher risk of developing BKV-HC. In multivariate analysis, patients receiving cord blood units (CBUs) ( P =0.0005) and peripheral blood stem cells ( P =0.011) represented high-risk subgroups for developing BKV-HC. BK viremia was directly correlated to HC severity ( P =0.011) with a 3 to 6-log peak being likely associated with grades 3 or 4 HC. No correlation was found between BKV-HC and acute graft versus host disease or mortality rate. Patients with BKV-HC required a significantly longer duration of hospitalization ( P <0.0001), more RBC ( P =0.0003) and platelet transfusions ( P <0.0001). Over the 5-year study period, the financial cost of the complication was evaluated at €2 376 076 ($3 088 899). Strategies to prevent the occurrence of late-onset BKV-HC after allo-HSCT are urgently needed, especially in CBU and peripheral blood stem cell recipients. BK viremia correlates with the severity of the disease. Prospective studies are required to test prophylactic approaches.

Nocardiosis is a life-threatening opportunistic infection in immunocompromised patients. Herein, we present successful adjunctive use of liposomal nebulized amikacin and tedizolid in a recipient of allogeneic hematopoietic stem cell transplantation infected with Nocardia nova complex who presented multiple complications to conventional therapeutic options.

Outcome of patients with primary refractory/relapsed (R/R) acute myeloid leukemia (AML) remains dismal. Herein, we present a retrospective monocentric study of 24 very high-risk AML patients who received a combination of fractionated gemtuzumab ozogamicin (GO) with intermediate-dose cytarabine and daunorubicin as salvage therapy. Median age was 55.3 years. Diagnostic was secondary AML for 33% of them. Seven patients had favorable risk, 8 had intermediate-1 or intermediate-2, and 6 had unfavorable risk of AML according to the European LeukemiaNet prognostic index. Complete remission was achieved in 50% of cases (46% in refractory and 55% in relapsed AML) without excessive toxicity. Thirteen patients could be referred for transplant. Only allogeneic hematopoietic stem cell transplantation provided a benefit in this patient cohort with a 1-year overall survival of 50.7 versus 18.1% in the absence of transplantation. Patients treated with reduced intensity conditioning (RIC) showed a longer survival as compared to those undergoing myeloablative conditioning regimen mainly because of decreased toxicity. Our data suggest that salvage therapy with fractionated GO combined with intermediate-dose cytarabine and daunorubicin in very high-risk patients may serve as a potential bridge therapy to RIC transplant.

The more and more frequent and widespread use of acyclovir (ACV), but also the increasing number of immunocompromised patients might induce an increase in HSV (Herpes Simplex Virus) resistance. HSV resistance to ACV is mainly associated with mutations in the thymidine kinase (TK) gene although mutations in the DNA polymerase can be observed. Up to now, resistance of HSV to ACV was a major concern for immunocompromised patients with a frequency between 2.5 and 10%. This study aimed to reassess HSV resistance to ACV, during a ten year period, in immunocompetent and in immunocompromised patients (bone marrow transplant patients, solid organ transplant, HIV positive patients, cancer patients). From 2002 to 2011, 1538 patients positive for HSV were tested for the susceptibility of their virus to ACV (1044 immunocompetent and 494 immunocompromised). In immunocompetent patients, prevalence of resistance remains under 0.5%, whatever the period studies. In immunocompromised patients, a significant increase can be observed, from 4.3% during 2002-2006 (11/255 patients) to 13.4% during 2007-2011 (32/239) (p = 0.0002). This significant increase is mainly observed among bone marrow transplant patients in which the prevalence is 10% (5/52) during 2002-2006 and 38% (30/79) during 2007-2011 (p = 0.0002), whereas other types of immune deficiencies do not show an increase (1.3% versus 2.9%, p = 0.2). New chemotherapy protocols (FLAMSA) and type of transplantation as blood cord transplant are part of the explanation. Genotyping of the resistant viruses (35 viruses) reveal mutations in the TK gene for 80% of them. Double population including resistant and susceptible viruses were recovered in 5 isolates (5/34 = 14%). Rapid diagnosis of HSV resistance, but also research on alternative treatment are more than ever of interest.

The more and more frequent and widespread use of acyclovir (ACV), but also the increasing number of immunocompromised patients might induce an increase in HSV (Herpes Simplex Virus) resistance. HSV resistance to ACV is mainly associated with mutations in the thymidine kinase (TK) gene although mutations in the DNA polymerase can be observed. Up to now, resistance of HSV to ACV was a major concern for immunocompromised patients with a frequency between 2.5 and 10%. This study aimed to reassess HSV resistance to ACV, during a ten year period, in immunocompetent and in immunocompromised patients (bone marrow transplant patients, solid organ transplant, HIV positive patients, cancer patients). From 2002 to 2011, 1538 patients positive for HSV were tested for the susceptibility of their virus to ACV (1044 immunocompetent and 494 immunocompromised). In immunocompetent patients, prevalence of resistance remains under 0.5%, whatever the period studies. In immunocompromised patients, a significant increase can be observed, from 4.3% during 2002–2006 (11/255 patients) to 13.4% during 2007–2011 (32/239) (p = 0.0002). This significant increase is mainly observed among bone marrow transplant patients in which the prevalence is 10% (5/52) during 2002–2006 and 38% (30/79) during 2007–2011 (p = 0.0002), whereas other types of immune deficiencies do not show an increase (1.3% versus 2.9%, p = 0.2). New chemotherapy protocols (FLAMSA) and type of transplantation as blood cord transplant are part of the explanation. Genotyping of the resistant viruses (35 viruses) reveal mutations in the TK gene for 80% of them. Double population including resistant and susceptible viruses were recovered in 5 isolates (5/34 = 14%). Rapid diagnosis of HSV resistance, but also research on alternative treatment are more than ever of interest.

Acute myeloid leukemia (AML) intensive chemotherapy combined with broad-spectrum antibiotics, leads to gut microbiota dysbiosis promoting pathological conditions and an increased incidence of complications. Here we report findings from a phase II single-arm, multicenter study evaluating autologous fecal microbiota transfer (AFMT) in 25 AML patients treated with intensive chemotherapy and antibiotics (ClinicalTrials.gov number: NCT02928523). The co-primary outcomes of the study are to evaluate the efficacy of AFMT in dysbiosis correction and multidrug-resistant bacteria eradication. The main secondary outcomes are to define a dysbiosis biosignature, to evaluate the effect of dysbiosis correction on patient clinical status, to assess the short and mid-term safety of AFMT in this immunocompromised population, and to evaluate the feasibility of the AFMT procedure and acceptability by the patient. Intensive induction chemotherapy induces a dramatic decrease of α-diversity indices, and a microbial dysbiosis with a significant shift of the microbial communities and domination of pro-inflammatory families. After AFMT treatment, α-diversity indices return to their initial mean levels and the similarity index shows the restoration of microbial communities. The trial meets pre-specified endpoints. AFMT appears to be safe and may be effective for gut microbiota restoration in AML patients receiving intensive chemotherapy and antibiotics, with an excellent gut microbiota reconstruction based on both richness and diversity indices at the species level. The combination of chemotherapy and broad-spectrum antibiotics induces gut microbiota (GM) dysbiosis in acute myeloid leukaemia (AML) leading to additional complications. Here, the authors report the efficacy in GM restoration and safety of autologous faecal microbiota transfer in treated AML patients in a phase II clinical trial.

Torque teno virus (TTV) has been proposed as a surrogate biomarker of T-cell function in allogeneic–haematopoietic–stem-cell transplantation (allo-HSCT). Conflicting data exists regarding the value of TTV to assess the degree of immunosuppression. The aim of the present study was to investigate the correlation between TTV viral load and immune function. Using samples from a prospective cohort composed of healthy-volunteers (HV) and allo-HSCT recipients at 6 months post-transplantation, we assessed the correlation between TTV viraemia and immune cell counts or T-cell proliferation capacity post-phytohaemagglutinin stimulation. TTV viraemia was detected in 68% of HV (n = 80) and 100% of allo-HSCT recipients (n = 41; p < 0.001); it was significantly higher in allo-HSCT recipients (3.9 vs. 2.1 Log copies/mL, p < 0.001). There was no correlation between T-cell function and CD3+T-cell count (rho: 0.002) suggesting that T-cell count can normalise without full functional recovery. Furthermore, no significant correlation was observed between TTV viraemia and absolute total/subset lymphocyte counts (rho: <0.13). The highest correlation was observed between TTV viral load and T-cell proliferation capacity (rho: −0.39). We therefore report an inverse correlation between T-cell function and TTV viraemia that is independent of T-cell count. Monitoring of TTV viraemia could be a fast suitable option to objectively assess the competence of immune function in at-risk populations.

Minimal residual disease (MRD) is now a powerful surrogate marker to assess the response to chemotherapy in acute myeloid leukemia (AML). DNMT3A mutation has been associated with adverse outcomes. In this study, we aimed to investigate the impact of DNMT3A status on NPM1 MRD predictive value for survival in a retrospective cohort of AML patients aged over 60 years old treated intensively. A total of 138 patients treated for NPM1-mutated AML in two French institutions were analyzed retrospectively. DNMT3A status did not influence the probability of having a ≥ 4log MRD1 reduction after induction. Only 20.4% of FLT3-ITD patients reached ≥ 4log MRD1 reduction compared to 47.5% in FLT3wt cases. A 4log reduction of NPM1 MRD was associated with a better outcome, even in FLT3-ITD mutated patients, independent of the allelic ratio. DNMT3A negative patients who reached a 4log reduction had a superior outcome to those who did not (HR = 0.23; p < 0.001). However, postinduction NPM1 MRD1 reduction was not predictive of OS and LFS in DNMT3Amut patients. These results confirm that post-induction NPM1 MRD1 is a reliable tool to assess disease outcome in elderly AML patients. However, the presence of DNMT3A also identifies a subgroup of patients at high risk of relapse.