No abstract

Patients diagnosed with acute leukemia (AL) have a weakened immune system. Infections acquired by these patients are cause for concern and especially worrisome when Gram-negative multidrug-resistant (MDR) bacteria are involved, as they are difficult to treat, especially in the case of ESBL- and/or carbapenemase-producing Enterobacterales. Culture-based approaches have been relied on over the past decades as the method of choice for the early detection of gut colonization by MDR Gram-negative bacteria. However, various studies have indicated its limited sensitivity, underlining the need for new screening procedures in onco-hematological patients. Here, we evaluated a shotgun metagenomics approach to detect ESBL- and/or carbapenemase-producing Enterobacterales in the gut of 28 patients who had recovered from AL, which were previously colonized by these bacteria but cured at the time of sampling, as judged by culture-based methods. No ESBL or carbapenemase determinants were detected among the many resistance genes found by the metagenomics approach, supporting that patients were truly decolonized, with considerable consequences for their future clinical management. Due to the relatively low number of patients available for the present investigation, further studies should be conducted to support the utility and applicability of metagenomics for the routine screening of MDR bacteria in onco-hematological patients.

BackgroundCPX‐351 is approved for the treatment of therapy related acute myeloid leukemia (t‐AML) and AML with myelodysplastic related changes (MRC‐AML). The benefits of this treatment over standard chemotherapy has not been addressed in well matched cohorts of real‐life patients.MethodsRetrospective analysis of AML patients treated with CPX‐351 as per routine practice. A propensity score matching (PSM) was used to compare their main outcomes with those observed in a matched cohort among 765 historical patients receiving intensive chemotherapy (IC), all of them reported to the PETHEMA epidemiologic registry.ResultsMedian age of 79 patients treated with CPX‐351 was 67 years old (interquartile range 62–71), 53 were MRC‐AML. The complete remission (CR) rate or CR without recovery (CRi) after 1 or 2 cycles of CPX‐351 was 52%, 60‐days mortality 18%, measurable residual disease <0.1% in 54% (12 out of 22) of them. Stem cell transplant (SCT) was performed in 27 patients (34%), median OS was 10.3 months, and 3‐year relapse incidence was 50%. Using PSM, we obtained two comparable cohorts treated with CPX‐351 (n = 52) or IC (n = 99), without significant differences in CR/CRi (60% vs. 54%) and median OS (10.3 months vs. 9.1 months), although more patients were bridged to SCT in the CPX‐351 group (35% vs. 12%). The results were confirmed when only 3 + 7 patients were included in the historical cohort. In multivariable analyses, SCT was associated with better OS (HR 0.33 95% CI: 0.18–0.59), p < 0.001.ConclusionLarger post‐authorization studies may provide evidence of the clinical benefits of CPX‐351 for AML in the real‐life setting.

Background: Background: FLT3 mutation is associated with adverse prognosis in AML (ELN2017, Dohner et al, Blood 2017) and Intensive chemotherapy (IC) has been the standard of treatment for FLT3 mutated AML for decades. Midostaurin (Midos) has been approved in combination with IC for FLT3-mutated AML based on an improvement in overall survival noted in the RATIFY phase 3 trial (Stone et al, N Engl J Med 2017) Aims: Aims: The aims of this study are to analyze safety and effectiveness of Midos plus IC in FLT3 AML, to validate RATIFY results in a "real-world" setting and to identify risk factors. Methods: Methods: We carried out a retrospective multicenter study (MDA-AML-2018-06) in 27 Spanish centers. Inclusion criteria: age >18 years, FLT3-mutated AML diagnosis according to WHO criteria and start of treatment with midostaurin in combination with IC between June 2016 and June 2021. We evaluated the response according to 2017 ELN criteria, toxicity according to CTCAE v4.0 and overall survival (OS) by Kaplan-Meier. Statistical analysis was performed using SPSS program version 20.0. Results:Results: A total of 175patients (pt) were included (93 female), median age 53 (18-76), of them 111were younger than 60yrs and 110pts had ECOG<2. ELN2017 stratification was favorable in 53pt; Intermediate: 72pt; adverse in 26pt. Median WBC count 44.500/µL (0.4-395.000). A total of 133pts had FLF3-ITD mutation and of them 74pt with ratio ≥0.5. Safety: Total Midos cycles 548 (median 2), 20 pt (11.5%) suffered QT prolongation, 26pt (14,8%) Midos interruption and 10pt (5.7%) Midos reduction. There were no deaths related to Midos. Effectiveness: 144 (81.4%) pt achieved CR after Induction1or2, of them 76pt were consolidated with alloSCT, 24pt received maintenance and 41pt proceed to W&W. Median OS for the whole population was not reached and the 24months OS was 68%. In our experience ELN2917 classification and ECOG<2 identify groups with differences in OS (p0.019 and p0.04 respectively). Age <60vs≥60 resulted in no differences for OS. We observed significant differences for maintenance versus W&W (p=0.001) in favorable and intermediate risk patients. Comparing maintenance vs alloSCT we observe no differences in the Intermediate ELN2017 group.