Allogreffe d'unités de sang placentaire et infections virales émergentes (exemple)

La cystite hémorragique à BK viras (CH-BKV) est une complication sévère et de plus en plus fréquente des allogreffes de cellules souches hématopoïétiques (CSH) avec un impact sur la morbi-mortalité. Nous avons analysé l'incidence, les facteurs de risque et les conséquences de l'apparition de CHBKV parmi 323 patients adultes allogreffés de CSH sur une période de cinq ans. Nous avons recherché une corrélation entre les virémies quantitatives et la sévérité de la CHBKV, nous avons décrit les traitements réalisés en nous focalisant sur l'utilisation du cidofovir et nous avons examiné le devenir, ainsi que l'impact médico-économique de la survenue de cette complication. Quarante-trois patients ont développé une CH-BKV avec une incidence en augmentation au cours des années 2009 et 2011. En analyse univariée, l'âge jeune (p=0.028), un donneur non apparenté (p=O.Ol78), la source des CSH (p=O.OOOl), un mismatch HLA (p=0.0022) et l'utilisation de busilvex dans le conditionnement (p=O.Ol) sont associés à une augmentation du risque de CHBKV. En analyse multivariée, les patients receveurs d'unités de sang placentaire (p=O,OOOS) et de cellules souches périphériques (p=O,O 11) représentent les sous-groupes les plus à risque de CHBK V. La virémie quantitative du BKV est était directement corrélée à la sévérité de la CHBKV (p=O,Oll). Nous ne retrouvons pas de relation entre l'apparition d'une CHBKV, l'existence d'une maladie du greffon contre l'hôte aiguë et d'impact sur la survie globale. Les patients atteints de CHBKV sont hospitalisés significativement plus longtemps que les autres (50 vs 40 jours; p<O,OOOl) et requièrent de transfusions globulaires et plaquettaires significativement plus nombreuses (12 vs 6; p=0,0003 et 20 vs 7; p<O,OOOl, respectivement) ce qui entraîne un impact médico-économique majeur. Des stratégies de prévention de la CHBKV sont urgentes, particulièrement pour les patients receveurs de sang placentaire et de cellules souches périphériques. La virémie quantitative pourrait être utile dans la surveillance de l'apparition de cette complication. Des études prospectives sont nécessaires pour tester des approches prophylactiquesLYON1-BU Santé (693882101) / SudocSudocFranceF

Qualitative, Exploratory, and Multidimensional Study of Telepresence Robots for Overcoming Social Isolation of Children and Adolescents Hospitalized in Onco-Hematology

Online Ahead of Print:October 30, 2019International audiencePurpose: Treatment of pediatric cancers and hematological malignancies requires long periods of isolation in a sterile room. To promote family connections, telepresence robots have been made available in the homes of hospitalized patients. Our aim was to evaluate the perceived benefits and difficulties encountered by users and their families in terms of family dynamics. We also evaluated the presence of the robot on the medical caregivers' therapeutic relationship and organization of daily care. Methods: An observational study was undertaken with semistructured face-to-face interviews of 17 patients (aged 7 to 25 years) and their parents conducted by a psychologist on day +15 after provision of the robot and then after the patients had gone home, as well as face-to-face interviews of 15 caregivers by a philosopher before the robots were made available and at day +21. Results: One of the main perceived benefits expressed by the patients was maintenance of a connection with their siblings and retention of their role in the family. For parents, the device provided reassurance of being able to stay in touch with their child. The nursing staff indicated that the devices allowed them to develop more than a professional relationship with the child and to interact with their extended family. Limitations of the virtual nature of the nursing staff/family relationship were also noted, such as potential frustration for patients when they witness things that they cannot access and a degree of concern for the parents during periods of disconnection. Conclusions: This study revealed an overall perceived benefit for patients, their families, and caregivers. It also highlighted relevant issues and it provides guidelines for broader application of such devices

Class I/Class II HLA Evolutionary Divergence Ratio Is an Independent Marker Associated With Disease-Free and Overall Survival After Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia

International audienceClass I Human Leukocyte Antigen (HLA) evolutionary divergence (HED) is a metric which reflects immunopeptidome diversity and has been associated with immune checkpoint inhibitor responses in solid tumors. Its impact and interest in allogeneic hematopoietic stem cell transplantation (HCT) have not yet been thoroughly studied. This study analyzed the clinical and immune impact of class I and II HED in 492 acute myeloid leukemia (AML) recipients undergoing HCT. The overall cohort was divided into a training (n=338) and a testing (n=132) set. Univariate cox screening found a positive impact of a high class I HED and a negative impact of a high class II HED on both disease-free (DFS) and overall survival (OS). These results were combined in a unique marker, class I/class II HED ratio, and assessed in the testing cohort. The final multivariate cox model confirmed the positive impact of a high versus low class I/class II HED ratio on both DFS (Hazard Ratio (HR) 0.41 [95% CI 0.2-0.83]; p=0.01) and OS (HR 0.34 [0.19-0.59]; p&lt;0.001), independently of HLA matching and other HCT parameters. No significant association was found between the ratio and graft-versus-host disease (GvHD) nor with neutrophil and platelet recovery. A high class I HED was associated with a tendency for an increase in NK, CD8 T-cell, and B cell recovery at 12 months. These results introduce HED as an original and independent prognosis marker reflecting immunopeptidome diversity and alloreactivity after HCT

Cidofovir in the Treatment of BK Virus-Associated Hemorrhagic Cystitis after Allogeneic Hematopoietic Stem Cell Transplantation

International audienceAfter allogeneic hematopoietic stem cell transplantation (HSCT), BK virus-associated hemorrhagic cystitis (BKV-HC) is a common complication. Although supportive measures have been the standard of care for many years, several studies suggested the efficacy of cidofovir. The aim of this study was to assess the safety profile and efficacy of cidofovir. A retrospective study was conducted on all patients treated with cidofovir in our HSCT unit between March 2011 and May 2013. Data for efficacy (partial [PR] or complete response [CR]), prescription (dose, frequency, number of doses, and administration route), and toxicity were collected from published reports and medical files. Renal toxicity was evaluated using creatinine clearance calculated with the Cockcroft and Gault formula. A parallel literature search using PubMed (last search, May 2015) was performed. From March 2011 to June 2013, 27 of 181 patients undergoing allogeneic HSCT in our department received cidofovir for BKV-HC: 24 (88.9%) intravenously, 1 intravesically, and 2 via both routes. Mean dose was 5 mg/kg per administration, for a median of 4 injections (range, 1 to 11), from twice a week to once every 2 weeks. CR was achieved in 22 patients (81.5%), PR in 2, and no response in 2 patients. Eight patients presented renal failure (29.6%): 6 moderate (creatinine clearance \\textless 60 mL/min) and 2 severe (creatinine clearance \\textless 30 mLmin). Mean decrease in creatinine clearance after cidofovir was 27% (35 mL/min; range, 2 to 159). In 3 cases renal insufficiency and hematologic toxicity led to discontinuation of treatment or switch to intravesical instillation. For 3 patients cidofovir dose was reduced because of nephrotoxicity. Thirteen studies have reported on the use of cidofovir for BKV-HC (204 patients) since 2005. Intravenous cidofovir was used for 91.3% of patients, with doses ranging from .5 to 5 mg/kg. The main toxicity reported was renal failure (9% to 50% in 9 studies). Between 60% and 100% of CRs were observed independently of cidofovir dose or administration route. Cidofovir is an effective therapy for BKV-HC but requires very precise renal function management to avoid toxicity. Cidofovir treatment modalities (high dose, intravesical instillation, or low dose

HHV-6 infection after allogeneic hematopoietic stem cell transplantation: From chromosomal integration to viral co-infections and T-cell reconstitution patterns

International audienceOBJECTIVES: Human herpes virus 6 (HHV-6) can reactivate after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and may be associated with significant clinical manifestations. METHODS: Case control study of HHV-6 infections after allo-HSCT. Chromosomal integration (ciHHV-6) for viral loads \\textgreater/= 5.5-log10 copies/mL was investigated. Viral co-infections, T-cell recovery, risk factors and outcome were compared in HHV-6- and non-HHV-6-infected patients. Antiviral treatment strategies were reviewed. RESULTS: Among 366 adult allo-HSCT recipients, 75 HHV-6 infections occurred. Three (4%) recipients were ciHHV-6. HHV-6 infections were associated with CMV (p = 0.05; sdHR 1.73, CI 0.99-3.02) and/or BKV infections (p \\textless 0.0001; sdHR 4.63, CI 2.04-10.53) but not EBV reactivation (p = 0.34). A slower CD8+ T-cells recovery was observed until 6 months after allo-HSCT in the HHV-6-infected group (p \\textless 0.001), independently of acute and/or chronic graft-versus-host disease. The overall probability of survival after allo-HSCT was diminished for active HHV-6-infected patients (p = 0.0326). Cord blood unit recipients had a higher risk of developing HHV-6 infection compared to bone marrow recipients (p = 0.0007; sdHR 3.82, CI 1.76-8.27). Anti-HHV-6 treatment achieved complete response in only 2/3 of the cases. CONCLUSIONS: In this series of allo-HSCT recipients, 4% were ciHHV-6, active HHV-6 infection was likely associated with CMV and BKV co-reactivations, delayed CD8+ T-cell recovery and poorer outcom

The odyssee study: prevention of dysbiosis complications with autologous fecal microbiota transfer (fmt) in acute myeloid leukemia (aml) patients undergoing intensive treatment: results of a prospective multicenter trial

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Gut microbiota diversity after autologous fecal microbiota transfer in acute myeloid leukemia patients

International audienceAcute 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