Abstract
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.
Outcome of patients undergoing allogenic hematopoietic stem cell transplantation (allo-HSCT) has improved. To investigate if this improvement can be transposed to the ICU setting, we conducted a ...systematic review and meta-analysis to assess short-term mortality of critically ill allo-HSCT patients admitted to the ICU and to identify prognostic factors of mortality. Public-domain electronic databases, including Medline via PubMed and the Cochrane Library were searched. All full-text articles written-English studies published from 2006 to 2016, including allo-HSCT adults transferred to the ICU were included. Eighteen studies were selected, including 2342 patients. Overall estimated ICU mortality was 51.7%. Prognostic factors associated with an increased ICU mortality were mechanical ventilation (OR = 12.2, 95% CI = 6.2-23.7), vasopressors (OR = 6.3, 95% CI = 3.6-11.1), renal replacement therapy (OR = 4.2, 95% CI = 2.8-6.2), ICU admission for acute respiratory failure (OR = 2.2, 95% CI = 1.1-4.4), acute kidney injury (OR = 2.2, 95% CI = 1.3-4), and acute graft-versus-host disease (OR = 1.6, 95% CI = 1.1-2.3). Factors associated with an increased ICU survival were a single-organ failure (OR = 0.2, 95% CI = 0.1-0.4), neurological failure (OR = 0.4, 95% CI = 0.2-0.8), and reduced-intensity conditioning regimens (OR = 0.7, 95% CI = 0.5-0.9). Septic shock, underlying malignancy, disease status, donor, and graft source did not impact prognosis. Outcome has improved, supporting the usefulness of ICU management. Organ failures at ICU admission, organ support requirement, and GVHD are the main prognostic factors.
High-flow nasal cannula (HFNC) is increasingly used in critically ill cancer patients with acute respiratory failure (ARF) to avoid mechanical ventilation (MV). The objective was to assess prognostic ...factors associated with mortality in ICU cancer patients requiring MV after HFNC failure, and to identify predictive factors of intubation. We conducted a retrospective study from 2012-2016 in a cancer referral center. All consecutive onco-hematology adult patients admitted to the ICU treated with HFNC were included. HFNC failure was defined by intubation requirement. 202 patients were included, 104 successfully treated with HFNC and 98 requiring intubation. ICU and hospital mortality rates were 26.2% (n = 53) and 42.1% (n = 85) respectively, and 53.1% (n = 52) and 68.4% (n = 67) in patients requiring MV. Multivariate analysis identified 4 prognostic factors of hospital mortality after HFNC failure: complete/partial remission (OR = 0.2, 95%CI = 0.04-0.98, p<0.001) compared to patients with refractory/relapse disease (OR = 3.73, 95%CI = 1.08-12.86), intubation after day 3 (OR = 7.78, 95%CI = 1.44-41.96), number of pulmonary quadrants involved on chest X-ray (OR = 1.93, 95%CI = 1.14-3.26, p = 0.01) and SAPSII at ICU admission (OR = 1.06, 95%CI = 1-1.12, p = 0.019). Predictive factors of intubation were the absence of sepsis (sHR = 0.32, 95%CI = 0.12-0.74, p = 0.0087), Sp02<95% 15 minutes after HFNC initiation (sHR = 2.05, 95%CI = 1.32-3.18, p = 0.0014), number of quadrants on X-ray (sHR = 1.73, 95%CI = 1.46-2.06, p60% at HFNC initiation (sHR = 3.12, 95%CI = 2.06-4.74, p<0.001) and SAPSII at ICU admission (sHR = 1.03, 95%CI = 1.02-1.05, p<0.01). Duration of HFNC may be predictive of an excess mortality in ARF cancer patients. Early warning scores to predict HFNC failure are needed to identify patients who would benefit from early intubation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We retrospectively examined the results of a new chemo-free approach combining blinatumomab with ponatinib (blina/pona) in 26 relapsed/refractory Philadelphia positive (Ph+) acute lymphoblastic ...leukemia (ALL) patients. All but one achieved complete morphologic remission, and 23 achieved a complete molecular response. With a median follow-up of 34.4 months, the median overall (OS) and event-free (EFS) survivals were 20 and 15.3 months, respectively. After blina/pona, 8 patients underwent an allotransplant (allo), while among the 18 non-transplanted cases, 15 received ponatinib in maintenance. Fifteen relapse/progressions occurred with a significant difference between allo and non allo cases (12.5% vs 82.3%, p = 0.003). However, OS and EFS were similar between both groups. Finally, blina/pona was well tolerated with eight reversible neurologic events and three cytokine release syndromes. Prospective studies are needed to properly assess the safety, tolerability and efficacy of the combination therapy.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Venetoclax is a BH3-mimetics agent specifically interacting with the antiapoptotic protein BCL-2, facilitating cytochrome c release from mitochondria, subsequent caspases activation, and cell death. ...Utilization of venetoclax has profoundly changed the landscape of treatment for the poor-prognosis category of AML patients unfit for intensive chemotherapy. In the phase III VIALE-A study, Venetoclax, in combination with the hypomethylating agent azacitidine, showed a 65% overall response rate and 14.7-month overall survival, in comparison with 22% and 8 months in the control arm. These results led to the widespread use of venetoclax in this indication. Other combination regimens, consisting of low-intensity, intensive, or targeted therapies are currently under evaluation. Despite promising results, preventing relapses or resistance to venetoclax is still an unmet clinical need. Numerous studies have been conducted to identify and overcome venetoclax resistance in preclinical models or in clinical trials, including the inhibition of other antiapoptotic proteins, the induction of proapoptotic BH3-only proteins, and/or the targeting of the mitochondrial metabolism and machinery.
Acute myeloid leukemias secondary (sAML) to myeloproliferative neoplasms (MPN) have variable clinical courses and outcomes, but remain almost always fatal. Large cohorts of sAML to MPN are difficult ...to obtain and there is very little scientific literature or prospective trials for determining robust prognostic markers and efficient treatments. We analyzed event‐free survival (EFS) and overall survival (OS) of 73 patients with MPN who progressed to sAML, based on their epidemiological characteristics, the preexisting MPN, the different treatments received, the different prognostic groups and the responses achieved according to the ELN, and their mutational status determined by next‐generation DNA sequencing (NGS). For 24 patients, we were able to do a comparative NGS analysis at both MPN and sAML phase. After acute transformation EFS and OS were respectively of 2.9 months (range: 0‐48.1) and 4.7 months (range: 0.1‐58.8). No difference in EFS or OS regarding the previous MPN, the ELN2017 prognostic classification, the first‐line therapy or the response was found. After univariate analysis, three genes, TP53, SRSF2 and TET2, impacted pejoratively sAML prognosis at sAML time. In multivariate analysis, TP53 (P = .0001), TET2 (P = .011) and SRSF2 (P = .018) remained independent prognostic factors. Time to sAML transformation was shorter in SRSF2‐mutated patients (51.2 months, range: 14.7‐98) than in SRSF2‐unmutated patients (133.8 months, range: 12.6‐411.2) (P < .001). Conventional clinical factors (age, karyotype, ELN2017 prognostic classification, treatments received, treatments response, Allo‐SCT…) failed to predict the patients' outcome. Only the mutational status appeared relevant to predict patients' prognosis at sAML phase.
Summary
Hepatic dysfunction (HD) is common in patients with haematological malignancies. Hepatic haemophagocytosis (HH) was detected in >50% of liver biopsies taken when HD remained unresolved after ...standard examination. We aimed to explore the contribution of liver biopsy in patients with both haematological malignancies and HD, describe the population of patients with HH, assess the prognostic impact of HH, and investigate haemophagocytic syndrome diagnostic score (HScore) utility in patients with HH. Between 2016 and 2019, 116 consecutive liver biopsies (76 transjugular, 40 percutaneous) were taken in 110 patients with haematological malignancy and HD (hyperbilirubinaemia, elevated transaminases, and/or cholestasis) and without a clear diagnosis. Liver biopsies were safe and diagnostically efficient. Predominant diagnoses included: HH (56%), graft‐versus‐host disease (55%), associated infections (24%), sinusoidal obstruction syndrome (15%), and tumoral infiltration (8%). Of patients, 35% were critically ill and 74% were allogeneic haematopoietic stem cell transplantation recipients, while 1‐year overall survival (OS) was 35% with HH versus 58% without HH (p = 0.026). The 1‐year OS was 24% with a HScore of ≥169 versus 50% with a HScore of <169 (p = 0.019). Liver biopsies are feasible in and contribute significantly to haematology patients with HD. HH occurred frequently and was associated with a poor prognosis. Combined with liver biopsy, the HScore may be helpful in refining haemophagocytic syndrome diagnosis.
Background Acute respiratory failure (ARF) is a life-threatening complication in onco-hematology patients. Optimal ventilation strategy in immunocompromised patients has been highly controversial ...over the last decade. Data are lacking on patients presenting with ARF associating isolated cardiac dysfunction or in combination with another etiology. The aim of this study was to assess prognostic impact of initial ventilation strategy in onco-hematology patients presenting ARF with associated cardiac dysfunction. Methods We conducted an observational retrospective study in Institut Paoli-Calmettes, a cancer-referral center, assessing all critically ill cancer patients admitted to the ICU for a ARF with cardiac dysfunction. Results Between 2010-2017, 127 patients were admitted. ICU and hospital mortality were 29% and 57%. Initial ventilation strategy was invasive mechanical ventilation (MV) in 21%. Others ventilation strategies were noninvasive ventilation (NIV) in 50%, associated with oxygen in 21% and high flow nasal oxygen (HFNO) in 29%, HFNO alone in 6% and standard oxygen in 23%. During ICU stay, 48% of patients required intubation. Multivariate analysis identified 3 independent factors associated with ICU mortality: SAPSII at admission (OR = 1.07/point, 95%CI = 1.03-1.11, p<0.001), invasive fungal infection (OR = 7.65, 95%CI = 1.7-34.6, p = 0.008) and initial ventilation strategy (p = 0.015). Compared to NIV, HFNO alone and standard oxygen alone were associated with an increased ICU mortality, with respective OR of 19.56 (p = 0.01) and 10.72 (p = 0.01). We realized a propensity score analysis including 40 matched patients, 20 in the NIV arm and 20 receiving others ventilation strategies, excluding initial MV patients. ICU mortality was lower in patients treated with NIV (10%), versus 50% in the other arm (p = 0.037). Conclusion In onco-hematology patients admitted for ARF with associated cardiac dysfunction, severity at ICU admission, invasive fungal infections and initial ventilation strategy were independently associated with ICU mortality. NIV was a protective factor on ICU mortality.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Prophylactic platelet transfusions (PT) aim to reduce bleeding. We assessed whether restrictive PT compared to prophylactic strategy could apply in ICU.
We conducted a retrospective monocentric study ...including patients >18 yo with haematological malignancy admitted to the ICU with thrombocytopenia <20 G/L between 2018 and 2021. Patients were classified in 2 groups according transfusion strategy applied during the first 3 days: prophylactic or restrictive transfusion.
180 patients were included, 87 and 93 in the restrictive and prophylactic groups respectively. After propensity-score analysis, 2 groups of 54 matched patients were analyzed. Restrictive strategy led to a significant reduction in PT with incidence rate for 100-ICU-patients-days of 34.9 and 49.9, incidence rate ratio = 0.699 0.5–0.9, p = 0.006, representing a 31% decrease. Decreased PT persisted until day 28 with platelet concentrates transfusions-free days at day 28 of 21 13–25 and 16.5 10.2–21 in the 2 groups (p = 0.04). Restrictive strategy did not result in higher grade ≥ 2 bleeding. Transfusion efficiency was low with similar number of days with platelet <10 or < 20 G/L regardless of strategy. Platelet transfusion strategy was not associated with 28-day mortality. Platelet nadir <5G/L was associated with day-28 mortality with HR = 1.882 1.011–3.055, p = 0.046.
A restrictive PT strategy appears feasible in the ICU.
•A restrictive platelet transfusion strategy in ICU reduces the use of platelet concentrates in haematology patients•This strategy is not associated with a greater occurrence of grade ≥ 2 bleeding•This strategy is not associated with short-term mortality
ObjectivesAcute myeloid leukaemia (AML) and high-risk myelodysplastic syndromes (MDS) are often treated with intensive chemotherapy followed by allogeneic haematopoietic stem cell transplantation ...(allo-HSCT). The pretransplant treatment results in a general deterioration of the patient’s health and quality of life. Furthermore, allo-HSCT can be responsible for significant toxicity with risks of graft-versus-host disease (GvHD). Developing strategies to prevent physical deconditioning, undernutrition and psychological distress could help maintain a satisfactory general state of health before transplantation and thus limit these deleterious effects. This protocol evaluates the feasibility and adherence to a personalised prehabilitation programme, which can be modulated and assisted by connected objects, provided from the diagnosis to the allo-HSCT.Methods and analysisThis multicentre interventional study will include 50 patients treated for AML or high-risk MDS with intensive chemotherapy and eligible for allo-HSCT. The intervention consists of a coached, supervised or self-directed physical activity programme, organised during the hospitalisation phases and periods at home. At the same time, patients will receive a weekly dietary follow-up. The whole intervention is controlled and modulated through the use of a dedicated application and connected objects allowing adaptation and individualisation. The rate of participation in the prescribed physical activity sessions will assess the feasibility of this study. In addition, the evolution of physical capacities (Short Physical Performance Battery, grip and quadriceps strengths), psychosocial parameters (Functional Assessment of Cancer Therapy - Leukaemia, Functional Assessment of Cancer Therapy - Fatigue, subjective well-being, Hospital Anxiety and Depression Scale, self-efficacy, Coach-Athlete Relationship Questionnaire, interviews) and clinical status (weight, lean body mass, survival rate, number of infections, days of hospitalisation, GvHD) will be evaluated.Ethics and disseminationThe study procedures have been approved by the National Ethics Committee (21.00223.000003). Consent is given in person by each participant. The information collected on the participants contains only a non-identifiable study identifier. The results of this protocol will be published in a scientific paper and communicated to the medical staff of the medical centre.Trial registration numberNCT03595787.
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