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Introduction: Elderly acute myeloid leukemia (AML) patients with poor‐risk cytogenetics have a poor outcome with intensive chemotherapy (IC). While Venetoclax (VEN) has changed the outcomes of elderly unfit patients treatment, it is unknown whether it could be effective in poor‐risk cytogenetics 60–75 years old patients. Materials and Methods: We included 60–75‐year‐old AML patients eligible to allogenic stem cell transplantation (allo‐SCT) treated with VEN (combined with azacitidine or with Cladribin and Aracytine) at Institut Paoli Calmettes, between 2020 and 2023 and compared this cohort with patients treated by IC between 2010 and 2019. Results: Twenty six patients were treated with VEN (17 in combination with azacitidine and 9 with Cladribin and Aracytine) and 90 were treated with IC. Thirteen patients (50%) had a TP53 mutation. The median time for leucocyte and platelet counts recovery was 26 days (range 0–103) and 26 days (range, 0–63). The median duration of the first hospitalization was 32 days (ranges, 7–79). The composite response rate was 69% (CR = 50%, CRi = 4%, MLFS = 15%). Allo‐SCT could be performed in 42% of cases. Median overall survival (OS) was 7.9 months (20.9 months in the group of patients who transitioned to allo‐SCT). We found no difference with the historical cohort of patients treated with IC except a trend toward less lower and upper tract gastro‐intestinal (GI) tract infections in the VEN group (respectively 8% vs 26%, p =.06; and 0% vs. 13% p =.06). Conclusion: VEN‐based treatment was found to be effective in high risk AML can be considered as an alternative to IC in patients aged 60–75 with adverse cytogenetics. [ABSTRACT FROM AUTHOR]

This document is a letter to the editor published in the journal Leukemia & Lymphoma. The letter discusses the long-term survival of patients with acute myeloid leukemia (AML) who have mutations in the nucleophosmin 1 (NPM1mut) gene. The study analyzed 179 newly diagnosed NPM1mut AML patients who were treated with intensive chemotherapy and had extensive molecular data available. The results showed that the presence of certain mutations, such as FLT3ITD and DNMT3AR882, significantly impacted overall survival. The study also identified a small group of patients who lived more than 5 years after AML diagnosis, and they were found to be younger and have fewer FLT3ITD mutations. [Extracted from the article]

This article discusses a case study of a 66-year-old man with acute myeloid leukemia who developed a disseminated Scedosporium invasive fungal infection. The patient initially presented with fatigue and fever and was diagnosed with AML-5b. He received intensive chemotherapy and developed complications including pulmonary lesions, enterocolitis, meningeal hemorrhage, and cutaneous lesions. Despite treatment with antifungals and antibiotics, the patient's condition worsened, and he ultimately died. The article highlights the challenges of diagnosing and treating rare fungal infections in hematology patients. [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]

Background: 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. Methods: 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. Results: 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, p<0.001), Fi02>60% 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). Conclusion: 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. [ABSTRACT FROM AUTHOR]

Simple Summary: The combination of venetoclax and azacititine (VEN–AZA) has recently been approved for the treatment of unfit newly diagnosed (ND) acute myeloid leukemia (AML) patients. Few data are available for the relapsed and/or refractory (R/R) AML group. We retrospectively compared the outcome of 39 R/R to 38 concomitant ND AML patients treated in our institution between 01/20 and 12/21. Response rates were lower in R/R AML (37% versus 56%); adverse cytogenetics was associated with treatment failure only in the R/R group (Relative Risk = 0.10, p = 0.005). ASXL1, IDH and SFSR2 mutations were associated with a trend in a higher response rate in the R/R group. Median leukemia-free survival was not different between the two groups (9.4 months and 10.3 months in the ND and R/R groups, respectively). In conclusion, VEN–AZA can be efficient as a salvage treatment for selected R/R AML patients. Venetoclax (VEN) belongs the BH3-mimetic class that selectively targets BCL-2, activating apoptosis. The combination of VEN and azacitidine (AZA) has changed the paradigm of treatment of newly diagnosed (ND) acute myeloid leukemia (AML) patients ineligible for intensive chemotherapy. There is scarce evidence for the use of VEN–AZA for relapsed or refractory (R/R) AML. We compared the outcome of 39 R/R AML and 38 ND AML patients treated between 01/20 and 12/21. The median age was 69 (22–86) and 73 (61–81) in the R/R and ND groups, respectively. Adverse cytogenetics were found in 36% of patients in the R/R group and 59% of patients in the ND group. Overall response rate was 37% in R/R AML, including 13% CR, 8% CRi, 3% PR and 13% MLFS, and 58% in the ND AML, including 32% CR, 13% CRi and 13% MLFS. Adverse cytogenetics was associated with treatment failure in the R/R group (Relative Risk = 0.13, p = 0.005). Median overall survival (OS) was 5.9 months in the R/R group and 9.4 months in the ND group. Median OS was 2.2 months in the adverse cytogenetics group versus 8.7 months in the intermediate cytogenetics group in the R/R group (p = 0.02). Median leukemia-free survival was not different between the two groups (9.4 months and 10.3 months), indicating that VEN–AZA can be an efficient salvage treatment for selected R/R AML patients. In conclusion, VEN–AZA is a promising treatment for ND AML and for selected R/R AML patients. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

We report the case of a patient with a history of Epstein-Barr virus-positive large B-cell lymphoma, who relapsed with an angioimmunoblastic T-cell lymphoma (AITL) associated with a chronic myelomonocytic leukaemia (CMML). We performed targeted next-generation sequencing on CMML and AITL DNA, which revealed mutations of TET2, DNMT3A, SRSF2, NRAS and IDH1, thus confirming that the spectrum of AITL mutations share similarities with myeloid disorders. The frequencies of TET2/DNMT3A and SRSF2 variants could support the hypothesis that TET2/DNMT3A mutations occurred in an early progenitor cell, which later progressed to both the AITL and CMML clones. Treatment with 5-azacytidine led to the complete remission of both diseases. Thus, targeting DNA methylation abnormalities in AITL may be an alternative strategy to chemotherapy. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

In 2005, the National Institutes of Health (NIH) proposed standard criteria for diagnosis, organ scoring and global assessment of chronic graft-versus-host disease (cGvHD) severity. We retrospectively reclassified cGvHD with NIH criteria in a monocentric cohort of 130 consecutive adult patients with hematological malignancies presenting cGvHD after receiving allo-hematopoietic stem cell transplant (HSCT) with a fludarabine-busulfan-antithymocyte globulin (ATG) conditioning regimen, among 313 consecutive HSCT recipients. We compared NIH and Seattle classifications to correlate severity and outcome. The follow up range was effectively 2-120 months. Forty-four percent developed Seattle-defined cGvHD (22% limited, 78% extensive forms). Using NIH criteria, there were 23%, 40% and 37% mild, moderate and severe forms, respectively, and 58%, 32% and 8% classic cGvHD, late acute GvHD and overlap syndrome. Five-year overall survival was 55% (49-61), and cumulative incidences of non-relapse mortality (NRM) and relapse/progression at 2 years were 19% (14-23) and 19% (14-24). NIH mild and moderate forms were associated with better survival compared to severe cGvHD (hazard ratio [HR] = 3.28, 95% confidence interval [CI]: 1.38-7.82, p = 0.007), due to higher NRM among patients with severe cGvHD (HR = 3.04, 95% CI: 1.05-8.78, p = 0.04) but comparable relapse risk ( p = NS). In conclusion, the NIH classification appears to be more accurate in predicting outcome mostly by the reclassification of old-defined extensive forms into NIH-defined moderate or severe. [ABSTRACT FROM AUTHOR]

ABSTRACT Acute myeloid leukemias (AMLs) are the hematological malignancies with the highest need for intensive care unit (ICU) admission due to their association with various life‐threatening situations. Limited data exist regarding the outcomes of elderly individuals with AML admitted to the ICU. However, current therapeutic protocols offer the potential for extended survival in this population. This retrospective, monocentric study focused on the outcomes of individuals aged ≥ 60 years admitted to the ICU for newly diagnosed AML. It included 139 patients admitted to the ICU at the Paoli‐Calmettes Institute between April 2010 and October 2020, during the initial phase of AML management. Patients were categorized into three groups based on the presence of biological criteria indicating “high risk” for complications (thrombocytopenia < 50 000/mm3 and leukocytosis > 50 000/mm3) and organ failure. Multiple logistic regression models were employed to identify predictive factors for in‐hospital and day 90 mortality, while Cox regression was used for 1‐year mortality. The rates of in‐hospital, day 90, and 1‐year mortality were 37%, 42%, and 60%, respectively. Variables associated with in‐hospital mortality included the Charlson Comorbidity Index, the need for invasive mechanical ventilation (MV), and multi‐organ failure. ELN17 risk was significantly associated with 1‐year mortality rates. This study demonstrates the benefits of ICU management for individuals aged ≥ 60 years during the initial phase of AML. It illustrates the effects of age, comorbidities, and the severity of organ failures on short‐term mortality and highlights the impact of classical prognostic markers on long‐term mortality. [ABSTRACT FROM AUTHOR]

Simple Summary: Venetoclax is a BH3-mimetics that specifically inhibits the antiapoptotic protein BCL-2. The drug has considerably expanded the treatment options of acute myeloid leukemia (AML) patients unfit for intensive treatment regimens. In recent phase III trials, combination of venetoclax with the hypomethylating agents azacitidine or with low dose cytarabine, was associated with a 48–65% response rate and a 7.2–14.7 months overall survival. Recent studies also suggest that the drug is highly efficient in combination with high-dose chemotherapy and targeted therapeutics, including IDH and FLT3 inhibitors. In this review, we summarize the molecular basis of BCL-2 inhibition in AML, the effect of venetoclax in preclinical models and clinical studies and discuss the main molecular pathways and therapeutic options for overcoming venetoclax resistance. Identifying new therapeutic strategies increasing BH3 mimetics activity and/or sensitizing toward apoptotic cell death will represent a major challenge for treating AML patients in the near future. 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. [ABSTRACT FROM AUTHOR]

Neutropenic enterocolitis (NE) is a diagnostic and therapeutic challenge associated with high mortality rates, with controversial opinions on its optimal management. Physicians are usually reluctant to select surgery as the first-choice treatment, concerns being raised regarding the potential risks associated with abdominal surgery during neutropenia. Nevertheless, no published studies comforted this idea, literature is scarce and surgery has never been compared to medical treatment. This review and meta-analysis aimed to determine the prognostic impact of abdominal surgery on outcome of neutropenic cancer patients presenting with NE, versus medical conservative treatment. This meta-analysis included studies analyzing cancer patients presenting with NE, treated with surgical or medical treatment, searched by PubMed and Cochrane databases (1983-2016), according to PRISMA recommendations. The endpoint was hospital mortality. Fixed-effects models were used. The meta-analysis included 20 studies (385 patients). Overall estimated mortality was 42.2% (95% CI = 40.2-44.2). Abdominal surgery was associated with a favorable outcome with an OR of 0.41 (95% CI = 0.23-0.74; p = 0.003). Pre-defined subgroups analysis showed that neither period of admission, underlying malignancy nor neutropenia during the surgical procedure, influenced this result. Surgery was not associated with an excess risk of mortality compared to medical treatment. Defining the optimal indications of surgical treatment is needed.Trial registration PROSPERO CRD42016048952 [ABSTRACT FROM AUTHOR]

In this article the authors discuss their study evaluating the Charlson Comorbidity Index (CCI), the Adult Comorbidity Evaluation-27 (ACE27) Index, and the Hemato-poietic Cell Transplantation-specific Comorbidity Index (HCT-CI) in elderly patients treated for acute lymphoblastic leukemia (ALL). Topics include the benefit/risk ratio of intensive chemotherapy in older ALL patients, induction chemotherapy, and maintenance treatment in ALL patients in remission.