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Abstract The use of peripheral blood (PB) or bone marrow (BM) stem cells graft in haploidentical hematopoietic stem cell transplantation with post-transplant cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis remains controversial. Moreover, the value of adding anti-thymoglobulin (ATG) to PTCy is unknown. A total of 1344 adult patients received an unmanipulated haploidentical transplant at 37 centers from 2012 to 2019 for hematologic malignancy. We compared the outcomes of patients according to the type of graft, using a propensity score analysis. In total population, grade II–IV and III–IV acute GVHD (aGVHD) were lower with BM than with PB. Grade III–IV aGVHD was lower with BM than with PB + ATG. All outcomes were similar in PB and PB + ATG groups. Then, in total population, adding ATG does not benefit the procedure. In acute leukemia, myelodysplastic syndrome and myeloproliferative syndrome (AL-MDS-MPS) subgroup receiving non-myeloablative conditioning, risk of relapse was twice greater with BM than with PB (51 vs. 22%, respectively). Conversely, risk of aGVHD was greater with PB (38% for aGVHD II–IV; 16% for aGVHD III–IV) than with BM (28% for aGVHD II–IV; 8% for aGVHD III–IV). In this subgroup with intensified conditioning regimen, risk of relapse became similar with PB and BM but risk of aGVHD III–IV remained higher with PB than with BM graft (HR = 2.0; range [1.17–3.43], p = 0.012).

Abstract Background The 4th European Conference on Infections in Leukemia recommends early adaptation of empirical antibiotic therapy (EAT) for febrile neutropenia in stable patients. Objectives To assess the efficacy of an antimicrobial stewardship (AMS) intervention promoting early de-escalation and discontinuation of EAT in high-risk neutropenic patients. Methods This before-after study was conducted in the hematology department of the University Hospital of Nice, France. The AMS intervention included the development of clinical decision support algorithms, a twice-weekly face-to-face review of all antibiotic prescriptions and monthly feedback on the intervention. The primary endpoint was overall antibiotic consumption during hospital stay, expressed as days of therapy (DOT). Results A total of 113 admissions were included: 56 during the pre-intervention period and 57 during the intervention period. Induction chemotherapy and conditioning for allogeneic stem cell transplantation were the most frequent reasons for admission. In the intervention period, there was a significant decrease in overall antibiotic consumption (median DOT 20 vs. 28 days, p = 0.006), carbapenem consumption (median DOT 5.5 vs. 9 days, p = 0.017) and anti-resistant Gram-positive agents consumption (median DOT 8 vs. 11.5 days, p = 0.017). We found no statistical difference in the rates of intensive care unit admission (9% in each period) and 30-day mortality (5% vs. 0%, p = 0.243). Compliance with de-escalation and discontinuation strategies was significantly higher in the intervention period (77% vs. 8%, p

Abstract Background of the study AML classification tools have been developed to stratify the risk at AML diagnosis. There is a need to evaluate these tools in the current therapeutic era. Cohort characteristics In this retrospective study, we compared five classifiers: ELN 2017, ELN 2022, ALFA classifier, Papaemmanuil et al. classifier, and Lindsley et al. classifier, in a real‐life cohort of 281 patients newly diagnosed for AML in Nice University Hospital. In our cohort median age was 68 years old, sex ratio was M/F 56%/44%, performance status was lower than 2 in 73.1% of patients, AML subtype was “De novo” in 71.5%, “secondary” in 22.4%, and “therapy‐related” in 6.0% of patients. Intensive chemotherapy was used in 53.0% of patients, and non‐intensive chemotherapy in 40.6% of patients. Molecular analysis was available in a large majority of patients and the main mutations found were NPM1 (22.7%), DNMT3A (17.4%), TP53 (13.1%), TET2 (12.4%), and FLT3‐ITD (12.4%). Results In our findings, the comparison of overall survival between the three prognostic groups in the global cohort was statistically significant in all classifiers: ELN 2017 p

Abstract Personalized medicine is a challenge for patients with acute myeloid leukemia (AML). The identification of several genetic mutations in several AML trials led to the creation of a personalized prognostic scoring algorithm known as the Knowledge Bank (KB). In this study, we assessed the prognostic value of this algorithm on a cohort of 167 real life AML patients. We compared KB predicted outcomes to real‐life outcomes. For patients younger than 60‐year‐old, OS was similar in favorable and intermediate ELN risk category. However, KB algorithm failed to predict OS for younger patients in the adverse ELN risk category and for patients older than 60 years old in the favorable ELN risk category. These discrepancies may be explained by the emergence of several new therapeutic options as well as the improvement of allogeneic stem cell transplantation (aHSCT) outcomes and supportive cares. Personalized medicine is a major challenge and predictions models are powerful tools to predict patient's outcome. However, the addition of new therapeutic options in the field of AML requires a prospective validation of these scoring systems to include recent therapeutic innovations.

Summary: Background: Failure of gastrointestinal acute graft-versus-host disease (GI-aGvHD) to respond to steroid therapy is associated with limited further therapeutic options. We aimed to assess the safety and efficacy of the first-in-human use of the pooled allogeneic faecal microbiota, MaaT013, for the treatment of steroid-refractory GI-aGvHD. Methods: This prospective, international, single-arm, phase 2a study reports clinical outcomes from a 24-patient cohort with grade III-IV, steroid refractory GI-aGvHD treated with the pooled allogeneic faecal microbiota MaaT013. MaaT013 involved pooling faecal matter from 3 to 8 screened donors then transplanting the pooled batches into patients to treat GI-aGVHD. The 24 patients were treated in the HERACLES study (Aug 2018 to Nov 2020) at 26 sites in Europe and an additional 52 patients were treated in a compassionate use/expanded access program (EAP) in France (July 2018 to April 2021). The primary endpoint was GI response at day 28, defined as the proportion of patients with GI-aGvHD who had a complete response (CR) or very good partial response (VGPR). GvHD grading and staging were assessed according to the revised Glucksberg criteria. Adverse events and severe adverse events were monitored for 6 months and 12 months, respectively. The HERACLES study was registered with ClinicalTrials.gov (NCT03359980). Findings: Compared with single donors, MaaT013 is characterised by higher microbial richness and reduced variability across batches. At day 28 (D28), the GI-overall response rate (ORR) was 38% in the prospective population, including 5 complete responses (CR), 2 very good partial responses (VGPR) and 2 partial responses (PR). In the EAP, the GI-ORR was 58% (17 CR, 9 VGPR and 4 PR). The 12-month overall survival (OS) was 25% in the prospective study and 38% in the EAP. Regarding safety, five infectious complications, including 3 sepsis, could not be excluded from being related to the study procedure in HERACLES. Shotgun sequencing analyses of the identified strains suggest that none were found in MaaT013. In the EAP, 18 pharmacovigilance cases were reported among 52 treated patients, including 11 bacteraemia/sepsis. In HERACLES, we observed in stools from responding patients at D28 a higher microbiota richness and increased levels of beneficial bacteria, in particular butyrate producers, along with increased levels of short-chain fatty acid and bile acids. In contrast, stools from non-responding (NR) patients displayed increased levels of pathogenic pro-inflammatory bacteria along with increased systemic inflammatory parameters. Interpretation: Overall, MaaT013 was safe in this population of highly immunocompromised patients and was associated with responses in some patients with GI-aGvHD and deserves further investigation. Funding: MaaT Pharma.

Regulatory T cells (Tregs) are key mediators of the immune system. MicroRNAs (miRNAs) are a family of ~22 nucleotide non-coding RNAs that are processed from longer precursors by the RNases Drosha and Dicer. miRNA regulates protein expression posttranscriptionally through mRNA destabilization or translational silencing. A critical role for miRNA in Treg function was initially discovered when both Dicer and Drosha knockout (KO) mice were found to develop a fatal autoimmune disease phenotypically similar to Foxp3 KO mice.