Evaluating testicular tissue for future autotransplantation: focus on cancer cell contamination and presence of spermatogonia in tissue cryobanked for boys diagnosed with a hematological malignancy.

Study Question: What is the contamination rate by cancer cells and spermatogonia numbers in immature testicular tissue (ITT) harvested before the start of gonadotoxic therapy in boys with a hematological malignancy?

Summary Answer: Among our cohort of boys diagnosed with acute lymphoblastic leukemia (ALL) and lymphomas, 39% (n = 11/28) had cancer cells identified in their tissues at the time of diagnosis and all patients appeared to have reduced spermatogonia numbers compared to healthy reference cohorts.

What Is Known Already: Young boys affected by a hematological cancer are at risk of contamination of their testes by cancer cells but histological examination is unable to detect the presence of only a few cancer cells, which would preclude autotransplantation of cryobanked ITT for fertility restoration, and more sensitive detection techniques are thus required. Reduced numbers of spermatogonia in ITT in hematological cancer patients have been suggested based on results in a limited number of patients.

[Evaluation of blood cell morphology with the RBC Advanced Application: Which cut-offs are most needed for which specific abnormalities?].

The detection of erythrocyte morphological abnormalities is a valuable and sometimes overlooked element in the diagnostic management of anemias. The aim of this article is to evaluate the clinical performance of the different detection thresholds tested by our laboratory using the Cellavision RBC Advanced module, after manual reclassification by an experienced operator, and comparing them to the guidelines by the ICSH (International Council for Standardization in Haematology). We arbitrarily set thresholds at 1% for "critical" abnormalities (tear drop cells, target cells, schizocytes and spherocytes) except for sickle cells (threshold set at 0.

Short-term biological variation study of plasma hemophilia and thrombophilia parameters in a population of apparently healthy Caucasian adults.

Objectives: Biological variation (BV) data obtained in a standardized way is valuable to assess the analytical requirements and the utility of a reference interval. Our study aimed to determine the short-term BV of thrombophilia (protein S, protein C, activated protein C resistance (APCR) and factor VIII) and hemophilia (factors VIII, IX and XI) parameters in plasma. Coagulation factors V and XII were also evaluated.

Positive direct antiglobulin test in COVID-19 patients: Decision-making process.

In this unprecedented crisis of severe acute respiratory syndrome coronavirus 2 and its associated coronavirus disease 2019 (COVID-19), polymerase chain reaction and then serological testing platforms have been massively developed to face the important screening demand. Polymerase chain reaction and serological testing platforms are not the only actors impacted by the crisis, transfusion services are facing important difficulties. A positive direct antiglobulin test is frequently observed for patients encountering COVID-19.

Transcriptomic and genomic heterogeneity in blastic plasmacytoid dendritic cell neoplasms: from ontogeny to oncogenesis.

Oncogenesis and ontogeny of blastic plasmacytoid dendritic cell neoplasm (BPDCN) remain uncertain, between canonical plasmacytoid dendritic cells (pDCs) and AXL+ SIGLEC6+ DCs (AS-DCs). We compared 12 BPDCN to 164 acute leukemia by Affymetrix HG-U133 Plus 2.0 arrays: BPDCN were closer to B-cell acute lymphoblastic leukemia (ALL), with enrichment in pDC, B-cell signatures, vesicular transport, deubiquitination pathways, and AS-DC signatures, but only in some cases.

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.

Biological variation data and analytical specification goal estimates of the thrombin generation assay with and without thrombomodulin in healthy individuals.

Background: Evaluation of an individual's thrombin-generating capacity enables a global assessment of the coagulation cascade and is therefore thought to better reflect the clotting function of blood. However, the lack of standardization still hampers the use in routine clinical practice.

Methods: Nineteen healthy subjects were sampled once a week for 5 consecutive weeks.

Improvement in progressive multifocal leukoencephalopathy after pembrolizumab-induced immune reconstruction inflammatory syndrome in a patient with follicular lymphoma.

Progressive multifocal leukoencephalopathy (PML) may develop in follicular lymphoma patients treated with bendamustine-rituximab. In this report, treatment with pembrolizumab successfully inhibited the clinical progression of PML by promoting radiologically demonstrated immune restoration inflammatory syndrome (IRIS), allowing complete clearance of the virus. These findings may further support the use of pembrolizumab in PML with special consideration for the potential occurrence of IRIS.

A biological profile for diagnosis and outcome of COVID-19 patients.

Objectives As severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) pandemic is increasing its victims on a global scale with recurring outbreaks, it remains of outmost importance to rapidly identify people requiring an intensive care unit (ICU) hospitalization. The aim of this study was to identify Coronavirus Disease 2019 (COVID-19) biomarkers, to investigate their correlation with disease severity and to evaluate their usefulness for follow-up. Methods Fifty patients diagnosed with SARS-Cov-2 were included in March 2020.

How should we diagnose and treat blastic plasmacytoid dendritic cell neoplasm patients?

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive leukemia for which we developed a nationwide network to collect data from new cases diagnosed in France. In a retrospective, observational study of 86 patients (2000-2013), we described clinical and biological data focusing on morphologies and immunophenotype. We found expression of markers associated with plasmacytoid dendritic cell origin (HLA-DRhigh, CD303+, CD304+, and cTCL1+) plus CD4 and CD56 and frequent expression of isolated markers from the myeloid, B-, and T-lymphoid lineages, whereas specific markers (myeloperoxidase, CD14, cCD3, CD19, and cCD22) were not expressed.

Characterization of two new high-grade B-cell lymphoma cell lines with MYC and BCL2 rearrangements that are suitable for in vitro drug sensitivity studies.

High-grade B-cell lymphomas with MYC and BCL2 or BCL6 rearrangements are highly aggressive B-cell lymphomas called double-hit lymphomas (HGBL-DH). They are particularly refractory to standard treatments and carry a poor prognosis. Fragments of resected tumoral lymph nodes from two HGBL-DH patients were put in culture.

Reevaluation of ATR signaling in primary resting chronic lymphocytic leukemia cells: evidence for pro-survival or pro-apoptotic function.

ATM, primarily activated by DNA double-strand breaks, and ATR, activated by single-stranded DNA, are master regulators of the cellular response to DNA damage. In primary chronic lymphocytic leukemia (CLL) cells, ATR signaling is considered to be switched off due to ATR downregulation. Here, we hypothesized that ATR, though expressed at low protein level, could play a role in primary resting CLL cells after genotoxic stress.

Eliminating malignant cells from cryopreserved ovarian tissue is possible in leukaemia patients.

Reimplantation of cryopreserved ovarian tissue (OT) can successfully restore ovarian function in young cancer patients after gonadotoxic treatment. However, for patients with leukaemia, there is a risk of malignant cell transmission. Our objective was to evaluate minimal disseminated disease in OT from leukaemia patients and test a follicle isolation technique to obtain disease-free follicle suspensions.

Targeting DNA repair with aphidicolin sensitizes primary chronic lymphocytic leukemia cells to purine analogs.

Purine analogs are among the most effective chemotherapeutic drugs for the treatment of chronic lymphocytic leukemia (CLL). However, chemoresistance and toxicity limit their clinical use. Here, we report that the DNA polymerase inhibitor aphidicolin, which displayed negligible cytotoxicity as a single agent in primary CLL cells, markedly synergizes with fludarabine and cladribine via enhanced apoptosis.

Positive impacts of Patient Blood Management in total hip arthroplasty. Retrospective and prospective studies (N=700).

The study aimed to determine the impact of implementing a patient blood management (PBM) policy during total hip arthroplasty. Firstly, the authors collected retrospective data concerning blood consumption for all patients (N = 577) having undergone total hip arthroplasty between 2009 and 2011, other than for post-traumatic indications. During this period, no coherent blood management rules were in place.

A novel approach for BCR-ABL1 standardization to improve International Scale estimation.

Introduction: Standardization of BCR-ABL1 messenger RNA quantification by real-time PCR on the International Scale (IS) is critical for monitoring therapy response in chronic myelogenous leukaemia. Since 2006, BCR-ABL1 IS standardization is propagated along reference laboratories by calculating a laboratory-specific conversion factor (CF), co-ordinated in Europe through the European Treatment and Outcome Study project. Although this process has proven successful to some extent, it has not been achievable for all laboratories due to the complexity of the process and the stringent requirements in terms of numbers of samples to be exchanged.

Loss of mutL homolog-1 (MLH1) expression promotes acquisition of oncogenic and inhibitor-resistant point mutations in tyrosine kinases.

Genomic instability drives cancer progression by promoting genetic abnormalities that allow for the multi-step clonal selection of cells with growth advantages. We previously reported that the IL-9-dependent TS1 cell line sequentially acquired activating substitutions in JAK1 and JAK3 upon successive selections for growth factor independent and JAK inhibitor-resistant cells, suggestive of a defect in mutation avoidance mechanisms. In the first part of this paper, we discovered that the gene encoding mutL homolog-1 (MLH1), a key component of the DNA mismatch repair system, is silenced by promoter methylation in TS1 cells.

Genetic Risk Factors of Venous Thromboembolism in the East Algerian Population.

Many genetic risk factors have been identified for causing venous thromboembolism (VTE). Most of them affect the function of natural anticoagulant pathways, particularly the protein C system, although recent studies suggest a role of components of the hematopoietic pathway in the etiology of venous thrombosis. In this case-control study, we aimed to determine the frequency of prothrombin G20210A and factor V Leiden (FVL) G1691A polymorphisms and protein C, protein S, and antithrombin III deficiencies in the East Algerian population and to investigate whether these genetic factors are associated with VTE.

Evaluation of a human ovarian follicle isolation technique to obtain disease-free follicle suspensions before safely grafting to cancer patients.

Objective: To evaluate the safety of our follicle isolation procedure in a model of ovarian tissue artificially contaminated with cancer cells, then to improve the procedure to effectively eliminate malignant cells from follicle suspensions without altering viability.

Design: Prospective experimental study.

Setting: Gynecology research unit in a university hospital.

Management of pregnancy in paroxysmal nocturnal hemoglobinuria on long-term eculizumab.

Pregnancy in women with paroxysmal nocturnal hemoglobinuria (PNH) is associated with increased maternal and fetal complications, to such an extent that PNH has for long been considered a relative contraindication for pregnancy. The most serious life-threatening complications are venous thromboembolic events, the risk of which is increased by the hypercoagulable state related to pregnancy. Eculizumab, a C5 complement inhibitor, has revolutionized the treatment of PNH.

Is transplantation of a few leukemic cells inside an artificial ovary able to induce leukemia in an experimental model?

Purpose: To evaluate the tumor-inducing ability of a few leukemic cells xenotransplanted inside an artificial ovary.

Methods: Ten and 100 BV-173 leukemic cells were embedded in a fibrin matrix along with 50,000 human ovarian stromal cells, and grafted to the peritoneal bursa of 5 and 5 SCID mice respectively. Four mice grafted with 3x10(6) leukemic cells in fibrin served as positive controls.