Infantile pyknocytosis, a neonatal hemolytic anemia with Heinz bodies: A cohort study.

Infantile pyknocytosis (IP) is a rare, probably misestimated, cause of non-immune neonatal hemolytic anemia evolving in two phases: an initial phase with severe jaundice, followed by a second phase with hemolytic anemia, which may require neonatal intensive care. The diagnosis of IP is based on the transient presence on blood smear of hyperdense, contracted, and/or spiculated red blood cells (pyknocytes), associated with the spontaneous resolution of clinico-biological features and the exclusion of other causes. If the etiology remains undetermined, some contributing factors, such as oxidative stress, have been proposed. We report the description of 16 patients with IP aiming at clarifying the circumstances associated with the development of this acquired disorder. In the acute phase, the mean hemoglobin nadir and pyknocyte count were 7.8 g/dL and 11%, respectively, and strikingly, Heinz bodies were evident in 50% of the newborns, but in 100% after prolonged incubation (4 hours). A high proportion of Mediterranean or African ancestry was noted in newborns, as well as a significant number of peripartum events, such as respiratory distress. If the etiology of IP is certainly multifactorial, our series reinforces the role of oxidative stress, which may, at least in part, find origin in desaturation episodes in newborns.

White blood cells scattergram as a valuable tool for COVID-19 screening: A multicentric study.

INTRODUCTION: New tools have been developed to distinguish the COVID-19 diagnosis from other viral infections presenting similar symptomatology and mitigate the lack of sensitivity of molecular testing. We previously identified a specific "sandglass" aspect on the white blood cells (WBC) scattergram of COVID-19 patients, as a highly reliable COVID-19 screening test (sensitivity: 85.9%, specificity: 83.5% and positive predictive value: 94.3%). We then decided to validate our previous data in a multicentric study. METHODS: This retrospective study involved 817 patients with flu-like illness, among 20 centers, using the same CBC instrument (XN analyzer, SYSMEX, Japan). After training, one specialist per center independently evaluated, under the same conditions, the presence of the "sandglass" aspect of the WDF scattergram, likely representing plasmacytoid lymphocytes. RESULTS: Overall, this approach showed sensitivity: 59.0%, specificity: 72.9% and positive predictive value: 77.7%. Sensitivity improved with subgroup analysis, including in patients with lymphopenia (65.2%), patients presenting symptoms for more than 5 days (72.3%) and in patients with ARDS (70.1%). COVID-19 patients with larger plasmacytoid lymphocyte cluster (>15 cells) more often have severe outcomes (70% vs. 15% in the control group). CONCLUSION: Our findings confirm that the WBC scattergram analysis could be added to a diagnostic algorithm for screening and quickly categorizing symptomatic patients as either COVID-19 probable or improbable, especially during COVID-19 resurgence and overlapping with future influenza epidemics. The observed large size of the plasmacytoid lymphocytes cluster appears to be a hallmark of COVID-19 patients and was indicative of a severe outcome. Furthers studies are ongoing to evaluate the value of the new hematological parameters in combination with WDF analysis.

Hairy lymphoproliferations: a case report and review of the literature / Hémopathies à lymphocytes « chevelus ¼ : à propos d'un cas et revue de la littérature

Mature B-cell lymphoproliferation with hairy lymphocytes include Marginal Zone Splenic Lymphoma (SMZL), Hairy Cell Leukemia (HCL), Splenic Diffuse Red Pulp Lymphoma (SDRPL), and Variant Hairy Cell Leukemia (HCL-v), the two latter being provisional entities that appeared in the 2008 WHO classification. We report the case of a 75-year-old man who benefited from a diagnostic re-evaluation of his SMZL. The good clinical evolution, the flow cytometry investigation (HCL score < 3, SDRPL score > 3, strong CD180 and CD200/CD180 ratio < 0.5) and the histological assessment favored a SDRPL. This entity did not exist at the time of the diagnosis in 2006. The differential diagnosis between these diseases sometimes remains uneasy. Here are mentioned some practical clues to assess the diagnosis.

Les syndromes lymphoprolifératifs B matures avec des lymphocytes d'aspect « chevelus ¼ comprennent le lymphome splénique de la zone marginale splénique (SMZL), la leucémie à tricholeucocytes (HCL), le lymphome diffus de la pulpe rouge (SDRPL) et la leucémie à tricholeucocytes variante (HCL-v), ces deux dernières étant des entités provisoires apparues dans la classification OMS 2008. Nous rapportons le cas d'un homme de 75 ans qui a bénéficié d'une réévaluation diagnostique de son SMZL. En effet, la bonne évolution clinique, les données des explorations par cytométrie en flux (score HCL < score SDRPL > 3, CD180 fort et ratio CD200/CD180 < 0,5) et les données anatomopathologiques ont conclu à un SDRPL. Cette entité n'existait pas lors du diagnostic en 2006. Le diagnostic différentiel entre ces différentes pathologies n'étant pas toujours aisé, nous tenterons de donner quelques pistes pratiques pour conduire au diagnostic précis.

[Investigation of large granular lymphocytic leukemias: data from the laboratory of hematology at Nancy University Hospital, France]. / Investigation des leucémies à grands lymphocytes à grains : expérience d'un laboratoire d'hématologie.

Large granular lymphocytic leukemia (LGLL) is a rare clonal lymphoproliferative disorder from T or NK origin. PURPOSE: to report on the diagnostic and therapeutic management of LGLL investigated in the university hospital at Nancy, France. METHODS: retrospective (7 years) collection of clinical and biological data and patients' cohort analysis. RESULTS: Eight out of fifteen patients presented with neutropenia, including five profound neutropenia (neutrophils < 500 × 109/L). Four patients had an infection. Two patients have rheumatoid arthritis and an associated Felty's syndrome, one a Sweet syndrome. Two also suffered from chronic Lymphocytic Leukemia, and one from a diffuse large B-cell lymphoma. Twelve patients had LGLL-T and 3 had a chronic LGLL-NK. Eleven out of twelve patients had a clonal LGLL-T when polymerase chain reaction assessed. No KIR clonality was sought among the 3 LGL-NK patients. Five patients out of fifteen received immunosuppressive treatment. CONCLUSION: Although using simple and robust investigations, our series demonstrates a high heterogeneity in LGLL detection and assessment.

[Cancer in children with intellectual disabilities: Questioning and ethical issues]. / Cancer chez un enfant porteur de handicap intellectuel : questionnement et enjeux éthiques.

The Parents and Caregivers group in the face of ethics in pediatrics of the Île-de-France Ethics Area wondered about the association of the words Disability and Cancer by focusing on the study of the course of children with intellectual disability, treated for cancer. These situations are exceptional, the number of cases in France must not be more than fifty per year. We gathered the testimony of five families of children using a semi-directive survey taking up the journey from birth, announcement of the handicap, the diagnosis of cancer and its treatment. The verbatim show that each story is unique and rich in lessons, despite the feeling of "double penalty": "He did not deserve this, a handicap plus cancer is a lot for one person", "the shot moreover." A healthcare team was also interviewed and raised an additional question: "First, the double penalty… then, what's the point?" Through these testimonies, we sought to question the ethical principles of care, which can be shaken up in these extraordinary supported.

[Use of the multiparametric panel CD3/CD4/CD8/CD7/CD26/CD158k in the detection and use of flow cytometry of Sezary cells]. / Apport du panel multiparamétrique CD3 CD4 CD8 CD7 CD26 CD158k dans la détection et le suivi par cytométrie en flux des cellules de Sézary.

The Sezary syndrome has been defined by a triad combining erythrodermia, generalized lymphadenopathy, and the presence of circulating Sezary cells > 1 × 109/L characterized by a CD4+/CD8- phenotype with loss of one or more T antigens (mainly CD7 and/or CD26). We retrospectively reviewed the immunophenotypic profiles of 10 SS patients followed in our institution (University Hospital at Nancy, France). The application of the WHO criteria resulted in a diagnostic confirmation for 9 out of 10 cases. Since 2008, new diagnostic and staging criteria have been proposed, including the CD158k/KIR3DL2 receptor detection. The application of these new criteria to our cohort led us to notice a phenotypic heterogeneity of our cases but allowed to achieve a relevant diagnosis of Sezary syndrome in all cases, especially for patients with lymphopenia. The use of such a panel of monoclonal antibodies also optimized the follow-up of the patients.

NKX3.1 is a direct TAL1 target gene that mediates proliferation of TAL1-expressing human T cell acute lymphoblastic leukemia.

TAL1 (also known as SCL) is expressed in >40% of human T cell acute lymphoblastic leukemias (T-ALLs). TAL1 encodes a basic helix-loop-helix transcription factor that can interfere with the transcriptional activity of E2A and HEB during T cell leukemogenesis; however, the oncogenic pathways directly activated by TAL1 are not characterized. In this study, we show that, in human TAL1-expressing T-ALL cell lines, TAL1 directly activates NKX3.1, a tumor suppressor gene required for prostate stem cell maintenance. In human T-ALL cell lines, NKX3.1 gene activation is mediated by a TAL1-LMO-Ldb1 complex that is recruited by GATA-3 bound to an NKX3.1 gene promoter regulatory sequence. TAL1-induced NKX3.1 activation is associated with suppression of HP1-α (heterochromatin protein 1 α) binding and opening of chromatin on the NKX3.1 gene promoter. NKX3.1 is necessary for T-ALL proliferation, can partially restore proliferation in TAL1 knockdown cells, and directly regulates miR-17-92. In primary human TAL1-expressing leukemic cells, the NKX3.1 gene is expressed independently of the Notch pathway, and its inactivation impairs proliferation. Finally, TAL1 or NKX3.1 knockdown abrogates the ability of human T-ALL cells to efficiently induce leukemia development in mice. These results suggest that tumor suppressor or oncogenic activity of NKX3.1 depends on tissue expression.