Advantages of a genomic DNA-based NGS assay for detection of mutant NPM1 measurable residual disease in AML.

Mutations in the Nucleophosmin-1 (NPM1) gene are among the most common molecular aberrations in acute myeloid leukemia (AML). Various studies have established mutant NPM1 (mNPM1) as a faithful molecular measurable residual disease (MRD) marker with prognostic significance. Assessment of prognostic mNPM1 is included in the European LeukemiaNet (ELN) recommendations on MRD detection in AML.

Gut microbiome alterations at acute myeloid leukemia diagnosis are associated with muscle weakness and anorexia.

The gut microbiota makes critical contributions to host homeostasis, and its role in the treatment of acute myeloid leukemia (AML) has attracted attention. We investigated whether the gut microbiome is affected by AML, and whether such changes are associated with hallmarks of cachexia. Biological samples and clinical data were collected from 30 antibiotic- free AML patients at diagnosis and matched volunteers (1:1) in a multicenter, cross-sectional, prospective study.

Association between severe acute malnutrition in childhood and hematological disorders in adulthood: the Lwiro follow-up study in the Eastern Democratic Republic of the Congo.

Background: Despite growing evidence on the short-term deleterious effects of severe acute malnutrition (SAM) in childhood on hematopoiesis, little is known about the long-term hematological effects of SAM in low-income countries (LICs). Our study explored the association between childhood SAM and hematological disorders in adults 11 to 30 years after post-SAM nutritional rehabilitation.

Methods: This follow up study investigated 97 adults (mean age 32 years) treated for SAM during childhood in eastern Democratic Republic of the Congo (DRC) between 1988 and 2007.

Hypogammaglobulinemia, a new risk factor for hepatitis B virus reactivation : about two cases.

Reactivation of the hepatitis B virus (HBV) with immunosuppressive status has been well established, mainly due to medications such as immunosuppressive therapy like cytotoxic chemotherapy, rituximab and biologic therapy, immunosuppression after solid and bone-marrow transplantation or long-term corticosteroids therapy. We report here two cases of HBV reactivation due to global hypogammaglobulinemia. Regular HBV serologic screening and PCR for HBV-DNA should be applied for each patient with primary immunosuppressive status and history of chronic HBV infection.

Gut microbiota alterations induced by intensive chemotherapy in acute myeloid leukaemia patients are associated with gut barrier dysfunction and body weight loss.

Background & Aims: Acute myeloid leukaemia (AML) chemotherapy has been reported to impact gut microbiota composition. In this study, we investigated using a multi -omics strategy the changes in the gut microbiome induced by AML intense therapy and their association with gut barrier function and cachectic hallmarks.

Methods: 10 AML patients, allocated to standard induction chemotherapy (SIC), were recruited.

CYAD-01, an autologous NKG2D-based CAR T-cell therapy, in relapsed or refractory acute myeloid leukaemia and myelodysplastic syndromes or multiple myeloma (THINK): haematological cohorts of the dose escalation segment of a phase 1 trial.

Background: CYAD-01 is an autologous chimeric antigen receptor (CAR) T-cell product based on the natural killer (NK) group 2D (NKG2D) receptor, which binds eight ligands that are overexpressed in a wide range of haematological malignancies but are largely absent on non-neoplastic cells. Initial clinical evaluation of a single infusion of CYAD-01 at a low dose in patients with relapsed or refractory acute myeloid leukaemia, myelodysplastic syndromes, and multiple myeloma supported the feasibility of the approach and prompted further evaluation of CYAD-01. The aim of the present study was to determine the safety and recommended phase 2 dosing of CYAD-01 administered without preconditioning or bridging chemotherapy.

Case report: Chronic neutrophilic leukemia associated with monoclonal gammopathies. A case series and review of genetic characteristics and practical management.

Chronic neutrophilic leukemia (CNL) is a rare but potentially aggressive negative myeloproliferative neoplasm, characterized by sustained mature, neutrophilic leukocytosis. The discovery of key driver mutations in the colony-stimulating-factor-3 receptor () gene resulted in the updated World Health Organization (WHO) diagnostic criteria in 2016. A significant number of CNL cases have been associated with plasma cell dyscrasias, predominantly multiple myeloma (MM) and monoclonal gammopathy of unknown significance (MGUS).

Secreted mutant calreticulins as rogue cytokines in myeloproliferative neoplasms.

Mutant calreticulin (CALR) proteins resulting from a -1/+2 frameshifting mutation of the CALR exon 9 carry a novel C-terminal amino acid sequence and drive the development of myeloproliferative neoplasms (MPNs). Mutant CALRs were shown to interact with and activate the thrombopoietin receptor (TpoR/MPL) in the same cell. We report that mutant CALR proteins are secreted and can be found in patient plasma at levels up to 160 ng/mL, with a mean of 25.

Therapeutic activity of GARP:TGF-β1 blockade in murine primary myelofibrosis.

Primary myelofibrosis (PMF) is a myeloproliferative neoplasm characterized by the clonal expansion of myeloid cells, notably megakaryocytes (MKs), and an aberrant cytokine production leading to bone marrow (BM) fibrosis and insufficiency. Current treatment options are limited. TGF-β1, a profibrotic and immunosuppressive cytokine, is involved in PMF pathogenesis.

Prognostic Value of -Internal Tandem Duplication Residual Disease in Acute Myeloid Leukemia.

Purpose: The applicability of -internal tandem duplications (-ITD) for assessing measurable residual disease (MRD) in acute myeloid leukemia (AML) in complete remission (CR) has been hampered by patient-specific duplications and potential instability of -ITD during relapse. Here, we comprehensively investigated the impact of next-generation sequencing (NGS)-based -ITD MRD detection on treatment outcome in a cohort of patients with newly diagnosed AML in relation to established prognostic factors at diagnosis and other MRD measurements, ie, mutant and multiparameter flow cytometry.

Methods: In 161 patients with de novo -ITD AML, NGS was performed at diagnosis and in CR after intensive remission induction treatment.

Phase 3 trial of gilteritinib plus azacitidine vs azacitidine for newly diagnosed FLT3mut+ AML ineligible for intensive chemotherapy.

Treatment results for patients with newly diagnosed FMS-like tyrosine kinase 3 (FLT3)-mutated (FLT3mut+) acute myeloid leukemia (AML) ineligible for intensive chemotherapy are disappointing. This multicenter, open-label, phase 3 trial randomized (2:1) untreated adults with FLT3mut+ AML ineligible for intensive induction chemotherapy to receive gilteritinib (120 mg/d orally) and azacitidine (GIL + AZA) or azacitidine (AZA) alone. The primary end point was overall survival (OS).

Targets in MPNs and potential therapeutics.

Philadelphia-negative classical Myeloproliferative Neoplasms (MPNs), including Polycythemia Vera (PV), Essential Thrombocythemia (ET) and Primary Myelofibrosis (PMF), are clonal hemopathies that emerge in the hematopoietic stem cell (HSC) compartment. MPN driver mutations are restricted to specific exons (14 and 12) of Janus kinase 2 (JAK2), thrombopoietin receptor (MPL/TPOR) and calreticulin (CALR) genes, are involved directly in clonal myeloproliferation and generate the MPN phenotype. As a result, an increased number of fully functional erythrocytes, platelets and leukocytes is observed in the peripheral blood.

Updated recommendations on the use of ruxolitinib for the treatment of myelofibrosis.

Objectives: Myelofibrosis is a rare bone marrow disorder associated with a high symptom burden, poor prognosis, and shortened survival. While allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment for myelofibrosis, the only approved and reimbursed pharmacotherapy for non-HSCT candidates in Belgium is ruxolitinib.

Methods: These updated recommendations are based on a consensus reached during two meetings and provide guidance for ruxolitinib administration in myelofibrosis patients considering the particularities of Belgian reimbursement criteria.

MiR-15a-5p Confers Chemoresistance in Acute Myeloid Leukemia by Inhibiting Autophagy Induced by Daunorubicin.

Anthracyclines remain a cornerstone of induction chemotherapy for acute myeloid leukemia (AML). Refractory or relapsed disease due to chemotherapy resistance is a major obstacle in AML management. MicroRNAs (miRNAs) have been observed to be involved in chemoresistance.

Clinical outcomes in patients with Philadelphia chromosome-positive leukemia treated with ponatinib in routine clinical practice-data from a Belgian registry.

Data on clinical use of ponatinib are limited. This prospective registry aimed to evaluate outcomes of ponatinib treatment in routine practice over 3 years (2016-2019) in Belgium (NCT03678454). Patients with chronic myeloid leukemia (CML) or Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) were treated with ponatinib per current label.

miR-15a-5p and miR-21-5p contribute to chemoresistance in cytogenetically normal acute myeloid leukaemia by targeting PDCD4, ARL2 and BTG2.

Cytarabine and daunorubicin are old drugs commonly used in the treatment of acute myeloid leukaemia (AML). Refractory or relapsed disease because of chemotherapy resistance is a major issue. microRNAs (miRNAs) were incriminated in resistance.

Azacitidine and Venetoclax in Previously Untreated Acute Myeloid Leukemia.

Background: Older patients with acute myeloid leukemia (AML) have a dismal prognosis, even after treatment with a hypomethylating agent. Azacitidine added to venetoclax had promising efficacy in a previous phase 1b study.

Methods: We randomly assigned previously untreated patients with confirmed AML who were ineligible for standard induction therapy because of coexisting conditions, because they were 75 years of age or older, or both to azacitidine plus either venetoclax or placebo.