Allogeneic stem cell transplantation as a curative therapeutic approach for VEXAS syndrome: a case report.

TO THE EDITOR: VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a newly described entity linked to somatic mutation of UBA1, encompassing inflammatory disorders and hematological malignancies. Patients experiments symptoms related to inflammatory manifestations on the skin, joints, lungs. Most patients are refractory to usual anti-inflammatory or immunosuppressive treatments. Half of them will develop hematological diseases, mostly myelodysplastic syndromes. VEXAS patients with hematological malignancies have a poor outcome and no curative option has been described so far. Because in the first reported cohort of VEXAS patients the UBA1 mutation was only found in hematopoietic stem cells but not in fibroblasts, we hypothesized that bone marrow transplantation would provide a cure for the disease. Here we report the case of a VEXAS patient who successfully received an allogeneic hematopoietic stem cell transplantation as a curative option.

[Erythrocytic parameters Sysmex in a case of severe haemolysis]. / Utilisation des paramètres érythrocytaires Sysmex dans un cas d'hémolyse sévère.

We are reporting a case of severe haemolytic anemia with cold agglutinins which combines several spurious determinations. It shows the usefulness of the new erythrocytic parameters of the XE 5000 Sysmex, specially: red blood cells with optical count (RBC-O), GR-He (intra-erythocytic hemoglobin) and R-MFV (most frequent volume). Optical red blood cells act as a substitute for red cells count instead of impedance red cells and R-MFV as a substitute for MCV (mean cell volume). The hematocrit (HCT) is corrected thanks to the following formula: HCT=(RBC-O X R- MFV)/1000. Free plasmatic hemoglobin is included in the measure of hemoglobin by the analyzer but is not available for tissue oxygenation. So, hemoglobin (HGB) has to be corrected by the means of GR- He thanks to the following formula: HGB=(GR He x RBC-O)/10.

[Assessment of an immature platelet fraction (IFP%) in the diagnosis of thrombocytopenia]. / Valeur du pourcentage de plaquettes réticulées dans le diagnostic étiologique d'une thrombopénie.

Reticulated platelets are young platelets containing mRNA. They reflect the rate of thrombopoesis. The aim of this study was to evaluate the reliability of the percentage of reticulated platelets (IPF%) as a diagnostic test for thrombocytopenia pathogenesis. IPF% was measured using XE 2100 Sysmex. An IPF% reference range in 52 healthy individuals was established as 1-4.5% with a median 2.2%. In all the 13 patients with idiopathic thrombocytopenic purpura IPF% was increased (median 11.8, range 5.3-54.3%). Only 7 out of 18 patients with disseminated intravascular coagulation had high IPF% (median 5.4%, range 2.9-14.1%). Surprisingly, IPF% was increased in 17 out of 22 patients with acute leukaemia (median 9.7%, range 0.9-41.9%). In CIVD, IPF% values correlated with the severity of the illness. Increased values in acute leukaemia could not be explained by non specific staining but by delayed maturation of reticulated platelets. A high IPF% does not substantiate hyperdestructive thrombocytopenia but a diagnosis of idiopathic thrombocytopenic purpura should be questioned if IPF% is not raised.

Clinical and molecular variability in congenital dyserythropoietic anaemia type I.

Congenital dyserythropoietic anaemia (CDA) type I is a rare, inherited disorder characterised by ineffective erythropoiesis and macrocytic anaemia. Complex bone disease has only occasionally been associated with this disease. CDA I is caused by mutations in the CDAN1 gene encoding for codanin-1. Our aim was to characterise the CDAN1 mutation in eight unrelated patients with sporadic CDA I, three of whom had complex bone disease. Six novel mutations in the CDAN1 gene were identified. In two patients, one mutation and in another, both mutations were elusive. No patient was homozygous for a null-type mutation. However, one patient with complex bone disease was homozygous for a splice-site mutation (IVS-12+5G>A). Western blotting revealed that codanin-1 synthesis was 65% less than the control. Five single nucleotide polymorphisms (SNPs) previously unreported in the literature or the SNP database were also identified. Although the absence of codanin-1 is probably lethal, the presence of 35% of the protein was compatible with life but was associated with severe clinical manifestations. However, in most patients studied, no correlation could be established between the expected levels of codanin-1 or the nature of the mutation and the severity of the clinical manifestations.

Evaluation of the Sysmex Xe-2100 hematology analyzer in hospital use.

The Sysmex XE-2100 (Sysmex Corp. Kobe, Japan) is a latest-generation hematology analyzer. Its optical and electrical measuring technology is improved by the addition of flux cytometry, fluorescence, and differential lysis. Its analytical performance in terms of precision, reproducibility, linearity, carryover, and time stability was found to be entirely satisfactory. In addition, the results of 500 complete blood counts and differentials correlated perfectly with those obtained by the Coulter STKS (Beckman Coulter, Villapointe, France). The comparison of 500 leukocyte differential count results analyzed in parallel with optical microscopy and the XE-2100 were surprising, and favorable to the XE-2100. This analyzer provides the user with an undeniable feeling of security concerning its reliability in detecting and identifying anomalies in the automated leukocyte differential count. With a sensitivity of 96%, a negative predictive value (NPV) of 98%, and a false-negative (FN) rate of 4%, the XE-2100 has perhaps reached the technological limits for a machine performing morphological recognition of normal and pathological blood cells.