Phf6 truncating mutation drives leukemogenesis via disrupted epigenetic regulation in mice.

PHF6 Somatic Mutations and Their Functional Role in the Pathophysiology of Myelodysplastic Syndromes (MDS) and Acute Myeloid Leukemia (AML)

PHF6 - Somatic Mutations and Their Role in Pathophysiology of MDS and AML

The importance of genomic predictors for clinical outcome of hematological malignancies

Hereditary Predisposition to Acute Myeloid Leukemia in Older Adults.

Invasive aspergillosis (IA) continues to be a leading cause of morbidity and mortality in hematologic malignancy (HM) patients. We evaluated the prognostic factors for IA in HM patients. In this retrospective study, we included all HM patients diagnosed with proven or probable IA between June 1993 and June 2008. A total of 449 HM patients were analyzed, the majority of which (75%) had underlying leukemia. Multivariate logistic regression analysis showed that neutropenia for more than two weeks during IA, steroid use, and intensive care admission were independently associated with failure to respond to antifungal therapy, as well as increased IA-attributable mortality (all p-values < .01). Antifungal therapy with an antimold azole-containing regimen (voriconazole or posaconazole) was also independently associated with improved response to treatment, as well as decreased IA-attributable mortality (all p-values < .0001). Survival analysis showed that primary or salvage therapy with a regimen that contained antimold azoles was significantly associated with improved survival (p < .001). In HM patients, persistent neutropenia and the need for intensive care are associated with failure to respond to antifungal therapy. Use of novel antimold azoles, either as primary or salvage therapy, improves the overall outcome and IA-attributable death of HM patients with IA.

To compare end-of-life (EOL) care for solid tumor and hematologic malignancy (HM) patients. We collected data on the last 100 consecutive deceased HM and 100 consecutive deceased solid tumor patients who died prior to June 1st 2020, treated at a single center. We compared demographic parameters, cause of death as ascertained by review of medical records by two independent investigators, and EOL quality indicators including: place of death, use of chemotherapy or targeted/biologic treatment, emergency department visits as well as hospital, inpatient hospice and Intensive Care Unit admissions and the time spent as inpatient over the last 30 days of life; mechanical ventilation and use of blood products during the last 14 days of life. In comparison with solid tumor patients, HM patients more commonly died from treatment complications (13% vs. 1%) and unrelated causes (16% vs. 2%, p < .001 for all comparisons). HM patients died more frequently than solid tumor patients in the intensive care unit (14% vs. 7%) and the emergency department (9% vs. 0%) and less frequently in hospice (9% vs. 15%, p = .005 for all comparisons). In the 2 weeks prior to death HM patients were more likely than solid tumor patients to undergo mechanical ventilation (14% vs. 4%, p = .013), receive blood (47% vs. 27%, p = .003) and platelet transfusions (32% vs. 7%, p < .001); however, no statistical difference was found in use of either of chemotherapy (18% vs. 13%, p = .28) or targeted treatment (10% vs. 5%, p = .16). HM patients were more likely than solid tumor patients to undergo aggressive measures at EOL. Rarity of HM deaths, frequently caused by complications of treatment and unrelated causes, may affect treatment choices at EOL.

Impact and Function of Somatic PHF6 Mutations in Myeloid Neoplasms

Acute respiratory failure (ARF) is still the major cause of intensive care unit (ICU) admission for hematological malignancy (HM) patients although the advance in hematology and supportive care has greatly improved the prognosis. Clinicians have to make decisions whether the HM patients with ARF should be sent to ICU and which ventilation support should be administered. Based on the reported investigations related to management of HM patients with ARF, we propose a selection procedure to manage this population and recommend hematological ICU as the optimal setting to recuse these patients, where hematologists and intensivists can collaborate closely and improve the outcomes. Moreover, noninvasive ventilation (NIV) still has its own place for selected HM patients with ARF who have mild hypoxemia and reversible causes. It is also crucial to monitor the efficacy of NIV closely and switch to invasive mechanical ventilation at appropriate timing when NIV shows no apparent improvement. Otherwise, early IMV should be initiated to HM with ARF who have moderate and severe hypoxemia, adult respiratory distress syndrome, multiple organ dysfunction, and unstable hemodynamic. More studies are needed to elucidate the predictors of ICU mortality and ventilatory mode for HM patients with ARF.

BackgroundSeveral studies have shown that underlying cancer is a risk factor for progression of COVID-19 to severe illness and fatal outcome but there is very little data that specifies which underlying cancer puts this patient population at the highest risk. MethodsWe retrospectively collected de-identified data on 1115 cancer patients diagnosed with COVID-19 between January and November 2020, at 12 centers in Asia, Australia, Europe, North America, and South America. Patient characteristics including age, type of malignancy (hematologic malignancy [HM], lung cancer, and non-lung cancer were determined in association with severe illness as well as all-cause mortality within 30 days after COVID-19 diagnosis.ResultsBy multivariable logistic regression analysis, independent risk factors for 30-day mortality in cancer patients included age > 65 (OR 6.64; 95% CI 3.351to 12.55; p< 0.0001), ALC < 0.5 K/microliter (OR 2.10; 95% CI 1.16 to 3.79; p=0.014), and anemia at < 10g/dl (OR 2.41; 95% CI 1.30 to 4.44; p=0.005). Among cancer patients, the 30-day mortality rate was significantly higher in patients with lung cancer than in patients with non-lung cancer solid tumors, including those with lung metastases (22% vs 9%; p=0.001). Patients with HM tended to have higher 30-day mortality than patients with non-lung cancer solid tumors (13% vs 9% p=0.07) and tended to have a lower mortality rate than patients with lung cancer (p=0.07). Furthermore, HM patients were more likely to be lymphopenic and anemic at diagnosis as well as progress to LRTI and be placed on ventilatory support compared to non-lung cancer solid tumor patients ( p= or < 0.01). In addition, lung cancer and HM patients were more likely to develop hypoxia and require hospital admission than non-lung cancer solid tumor patients ( p=0.01). ConclusionLung cancer and HM patients are associated with the highest risk of progressing to severe disease and mortality in cancer patients with COVID-19. Hence, cancer patient population should be given the highest priority as far as prevention [vaccination with boosters if needed] as well as preemptive early therapy with monoclonal antibodies right after the onset of COVID-19.Disclosures Monica Slavin, MBBS,MD, F2G (Advisor or Review Panel member)Merck (Advisor or Review Panel member)Pfizer (Advisor or Review Panel member)

Background: The association between giant cell arteritis (GCA) and malignancies had been widely investigated with studies reporting conflicting results. Therefore, in this study, we aimed to investigate this association using a large nationwide electronic database. Methods: This study was designed as a retrospective cohort study including GCA patients first diagnosed between 2002–2017 and age, sex and enrollment time-matched controls. Follow-up began at the date of first GCA-diagnosis and continued until first diagnosis of malignancy, death or end of study follow-up. Results: The study enrolled 7213 GCA patients and 32,987 age- and sex-matched controls. The mean age of GCA diagnosis was 72.3 (SD 9.9) years and 69.1% were women. During the follow-up period, 659 (9.1%) of GCA patients were diagnosed with solid malignancies and 144 (2.0%) were diagnosed with hematologic malignancies. In cox-multivariate-analysis the risk of solid- malignancies (HR = 1.12 [95%CI: 1.02–1.22]), specifically renal neoplasms (HR = 1.60 [95%CI: 1.15–2.23]) and sarcomas (HR = 2.14 [95%CI: 1.41–3.24]), and the risk of hematologic malignancies (HR = 2.02 [95%CI: 1.66–2.47]), specifically acute leukemias (HR = 1.81 [95%CI: 1.06–3.07]), chronic leukemias (HR = 1.82 [95%CI: 1.19–2.77]), Hodgkin’s lymphomas (HR = 2.42 [95%CI: 1.12–5.20]), non-Hodgkin’s-lymphomas (HR = 1.66: [95%CI 1.21–2.29]) and multiple myeloma(HR = 2.40 [95%CI: 1.63–3.53]) were significantly increased in GCA patients compared to controls. Older age at GCA-diagnosis (HR = 1.36 [95%CI: 1.25–1.47]), male-gender (HR = 1.46 [95%CI: 1.24–1.72]), smoking (HR = 1.25 [95%CI: 1.04–1.51]) and medium-high socioeconomic status (HR = 1.27 [95%CI: 1.07–1.50]) were independently associated with solid malignancy while age (HR = 1.47 [95%CI: 1.22–1.77]) and male-gender (HR = 1.61 [95%CI: 1.14–2.29]) alone were independently associated with hematologic- malignancies. Conclusion: our study demonstrated higher incidence of hematologic and solid malignancies in GCA patients. Specifically, leukemia, lymphoma, multiple myeloma, kidney malignancies, and sarcomas. Age and male gender were independent risk factors for hematological malignancies among GCA patients, while for solid malignancies, smoking and SES were risk factors as well.

COVID-19 Immune Response in Hematologic Malignancies: Analysis of COVID-19 Anti-Spike Antibodies in Previously Infected and Uninfected Patients

Clinical characteristics and prognosis of bloodstream infections with carbapenem-resistant Gram-negative organisms in patients with hematological malignancies: A multicenter case-control study in China

End-of-Life Therapeutic Burden: A Comparative Study of Hematologic and Solid Tumor Malignancies

Outcomes and Risks of Allogeneic Hematopoietic Stem Cell Transplant for Hematological Malignancies in Patients with HIV Infection

Recurrent Gene Mutations in Pediatric Patients with AML By Targeted Sequencing ―the Jccg Study, JPLSG AML-05―