Body mass index affects imatinib exposure: Real-world evidence from TDM with adaptive dosing.

Background: Imatinib is the treatment of elderly or frail patients with chronic myeloid leukemia (CML). Trough levels of around 1000 ng/ml are considered as the target exposure.

Objectives: We searched for baseline parameters associated with imatinib pharmacokinetics, and studied the clinical impact of subsequent adaptive dosing.

Reactive oxygen species and aldehyde dehydrogenase 1A as prognosis and theragnostic biomarker in acute myeloid leukaemia patients.

Acute myeloid leukaemia (AML) remains a major unmet medical, despite recent progress in targeted molecular therapies. One aspect of leukaemic cell resistance to chemotherapy is the development of clones with increased capacity to respond to cellular stress and the production of reactive oxygen species (ROS), thanks in particular to a high aldehyde dehydrogenases (ALDH) 1A1/2 activity. At diagnosis, ROS level and ALDH1A1/2 activity in AML patients BM are correlated with the different ELN 2022 prognostic groups and overall survival (OS).

Poor prognosis of SRSF2 gene mutations in patients treated with VEN-AZA for newly diagnosed acute myeloid leukemia.

Mutations in spliceosome genes (SRSF2, SF3B1, U2AF1, ZRSR2) correlate with inferior outcomes in patients treated with intensive chemotherapy for Acute Myeloid Leukemia. However, their prognostic impact in patients treated with less intensive protocols is not well known. This study aimed to evaluate the impact of Spliceosome mutations in patients treated with Venetoclax and Azacitidine for newly diagnosed AML.

Persistent COVID-19: A Case Report of an Immunocompromised Patient and a Literature Review.

Introduction: Immunocompromised patients can show prolonged shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and persistent symptoms, which is called persistent COVID-19.

Case Presentation: We report a case of an immunocompromised patient who was treated for mantle cell lymphoma and was suffering from B-cell depletion. The patient developed persistent COVID-19, which was confirmed by real-time polymerase chain reaction (RT-PCR) tests in only sputum and bronchoalveolar fluid which remained positive for at least 112 days.

Single-Cell Transcriptome Analysis of Acute Myeloid Leukemia Cells Using Methanol Fixation and Cryopreservation.

Introduction: The application of single-cell RNA sequencing has greatly improved our understanding of various cellular and molecular mechanisms involved in physiological and pathophysiological processes. However, obtaining living cells for this technique can be difficult under certain conditions. To solve this problem, the methanol fixation method appeared as a promising alternative for routine clinical use.

Cytidine deaminase status as a marker of response to azacytidine treatment in MDS and AML patients.

Azacitidine (Aza) is a mainstay of treatment for patients with acute myeloid leukaemia (AML) ineligible for induction chemotherapy and other high-risk myelodysplastic syndromes (MDS). Only half of patients respond, and almost all will eventually relapse. There are no predictive markers of response to Aza.

The Contribution of Multiplexing Single Cell RNA Sequencing in Acute Myeloid Leukemia.

Decades ago, the treatment for acute myeloid leukemia relied on cytarabine and anthracycline. However, advancements in medical research have introduced targeted therapies, initially employing monoclonal antibodies such as ant-CD52 and anti-CD123, and subsequently utilizing specific inhibitors that target molecular mutations like anti-IDH1, IDH2, or FLT3. The challenge lies in determining the role of these therapeutic options, considering the inherent tumor heterogeneity associated with leukemia diagnosis and the clonal drift that this type of tumor can undergo.

Anti-Jo-1 autoantibodies: biomarkers of severity and evolution of the disease in antisynthetase syndrome.

Background: Anti-Jo-1 autoantibodies represent essential markers in the diagnosis of antisynthetase syndrome (ASS). In this retrospective study, we aimed to investigate whether their concentrations and fluctuations could both respectively reflect the severity and evolution of ASS.

Methods: Between 2015 and 2020, clinical and biological features of ASS patients with at least one positive measure of anti-Jo-1 autoantibody were collected.

Impact of Next-Generation Sequencing in Diagnosis, Prognosis and Therapeutic Management of Acute Myeloid Leukemia/Myelodysplastic Neoplasms.

For decades, the diagnosis, prognosis and thus, the treatment of acute myeloblastic leukemias and myelodysplastic neoplasms has been mainly based on morphological aspects, as evidenced by the French-American-British classification. The morphological aspects correspond quite well, in a certain number of particular cases, to particular evolutionary properties, such as acute myelomonoblastic leukemias with eosinophils or acute promyelocytic leukemias. Advances in biology, particularly "classical" cytogenetics (karyotype) and molecular cytogenetics (in situ hybridization), have made it possible to associate certain morphological features with particular molecular abnormalities, such as the pericentric inversion of chromosome 16 and translocation t(15;17) in the two preceding examples.

Cytological Diagnosis of Classic Myeloproliferative Neoplasms at the Age of Molecular Biology.

Myeloproliferative neoplasms (MPN) are clonal hematopoietic stem cell-derived disorders characterized by uncontrolled proliferation of differentiated myeloid cells. Two main groups of MPN, -positive (Chronic Myeloid Leukemia) and -negative (Polycythemia Vera, Essential Thrombocytosis, Primary Myelofibrosis) are distinguished. For many years, cytomorphologic and histologic features were the only proof of MPN and attempted to distinguish the different entities of the subgroup -negative MPN.

Determination of 5-azacitidine in human plasma by LC-MS/MS: application to pharmacokinetics pilot study in MDS/AML patients.

Purpose: Azacitidine (Vidaza®, AZA) is a mainstay for treating acute myeloid leukemia (AML) in patients unfit for standard induction and other myelodysplastic syndromes (MDS). However, only half of the patients usually respond to this drug and almost all patients will eventually relapse. Predictive markers for response to AZA are yet to be identified.

Impact of Molecular Biology in Diagnosis, Prognosis, and Therapeutic Management of -Negative Myeloproliferative Neoplasm.

-negative myeloproliferative neoplasms (MPNs) include three major subgroups-polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF)-which are characterized by aberrant hematopoietic proliferation with an increased risk of leukemic transformation. Besides the driver mutations, which are , more than twenty additional mutations have been identified through the use of next-generation sequencing (NGS), which can be involved with pathways that regulate epigenetic modifications, RNA splicing, or DNA repair. The aim of this short review is to highlight the impact of molecular biology on the diagnosis, prognosis, and therapeutic management of patients with PV, ET, and PMF.

Successful treatment with adapted high dose methotrexate in a hemodialysis patient with primary central nervous system lymphoma: 100mg/m seems sufficient.

High dose methotrexate (HD-MTX) based chemoimmunotherapy is a central part of the standard approach to treatment of primary central nervous system lymphoma (PCNSL). Renal dysfunction leads to delayed MTX complete elimination and critical MTX concentration. Despite the recommendations, hemodialysis status should not exclude HD-MTX.

Successful treatment with adapted high dose methotrexate in a hemodialysis patient with primary central nervous system lymphoma: 100mg/m seems sufficient.

High dose methotrexate (HD-MTX) based chemoimmunotherapy is a central part of the standard approach to treatment of primary central nervous system lymphoma (PCNSL). Renal dysfunction leads to delayed MTX complete elimination and critical MTX concentration. Despite the recommendations, hemodialysis status should not exclude HD-MTX.

Functional status in older patients with cancer.

Background: Functional Status (FS) is an important domain in Comprehensive Geriatric Assessment (CGA) and is most often evaluated using the Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL) scales separately.

Method And Objectives: This secondary analysis of a previous prospective cohort study was conducted between September 2015 and May 2018 at Marseille University Hospital, France, on 613 cancer outpatients aged ≥70 years. The first objective of this study was to determine the prevalence of FS impairment in older outpatients with cancer using a combination of the information collected with the ADL and short IADL scales.

The contribution of single-cell analysis of acute leukemia in the therapeutic strategy.

After decades during which the treatment of acute myeloblastic leukemia was limited to variations around a skeleton of cytarabine/anthracycline, targeted therapies appeared. These therapies, first based on monoclonal antibodies, also rely on specific inhibitors of various molecular abnormalities. A significant but modest prognosis improvement has been observed thanks to these new treatments that are limited by a high rate of relapse, due to the intrinsic chemo and immune-resistance of leukemia stem cell, together with the acquisition of these resistances by clonal evolution.

Phase I Trial of Prophylactic Donor-Derived IL-2-Activated NK Cell Infusion after Allogeneic Hematopoietic Stem Cell Transplantation from a Matched Sibling Donor.

: NK cell-based immunotherapy to prevent relapse after allogeneic transplantation is an appealing strategy because NK cells can provide strong antitumor effect without inducing graft-versus-host disease (GVHD). Thus, we designed a phase-I clinical trial evaluating the safety of a prophylactic donor-derived ex vivo IL-2 activated NK cell (IL-2 NK) infusion after allo-HSCT for patients with hematologic malignancies. : Donor NK cells were purified and cultured ex vivo with IL-2 before infusion, at three dose levels.