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Background: In this study, we primarily sought to assess the ability of flow cytometry to predict early clinical deterioration and overall survival in patients with sepsis admitted in the ED and ICU.Methods: Patients admitted for community-acquired acute sepsis from 11 hospital centers were eligible. Early (day 7) and late (day 28) deaths were notified. Levels of CD64pos granulocytes, CD16pos monocytes, CD16dim immature granulocytes (IGs), and T and B lymphocytes were assessed by flow cytometry using an identical, cross-validated, robust, and simple consensus standardized protocol in each center.Results: Among 1,062 patients screened, 781 patients with confirmed sepsis were studied (age, 67 ± 48 years; Simplified Acute Physiology Score II, 36 ± 17; Sequential Organ Failure Assessment, 5 ± 4). Patients were divided into three groups (sepsis, severe sepsis, and septic shock) on day 0 and on day 2. On day 0, patients with sepsis exhibited increased levels of CD64pos granulocytes, CD16pos monocytes, and IGs with T-cell lymphopenia. Clinical severity was associated with higher percentages of IGs and deeper T-cell lymphopenia. IG percentages tended to be higher in patients whose clinical status worsened on day 2 (35.1 ± 35.6 vs 43.5 ± 35.2, P = .07). Increased IG percentages were also related to occurrence of new organ failures on day 2. Increased IG percentages, especially when associated with T-cell lymphopenia, were independently associated with early (P < .01) and late (P < .01) death.Conclusions: Increased circulating IGs at the acute phase of sepsis are linked to clinical worsening, especially when associated with T-cell lymphopenia. Early flow cytometry could help clinicians to target patients at high risk of clinical deterioration.Trial Registry: ClinicalTrials.gov; No.: NCT01995448; URL: www.clinicaltrials.gov. [ABSTRACT FROM AUTHOR]

Calreticulin (CALR) mutations have recently been reported in 70–84% of JAK2V617F-negative myeloproliferative neoplasms (MPN), and this detection has become necessary to improve the diagnosis of MPN. In a large single-centre cohort of 298 patients suffering from Essential Thrombocythemia (ET), the JAK2V617F, CALR and MPL mutations were noted in 179 (60%), 56 (18.5%) and 13 (4.5%) respectively. For the detection of the CALR mutations, three methods were compared in parallel: high-resolution melting-curve analysis (HRM), product-sizing analysis and Sanger sequencing. The sensitivity for the HRM, product-sizing analysis and Sanger sequencing was 96.4%, 98.2% and 89.3% respectively, whereas the specificity was 96.3%, 100% and 100%. In our cohort, the product-sizing analysis was the most sensitive method and was the easiest to interpret, while the HRM was sometimes difficult to interpret. In contrast, when large series of samples were tested, HRM provided results more quickly than did the other methods, which required more time. Finally, the sequencing method, which is the reference method, had the lowest sensitivity but can be used to describe the type of mutation precisely. Altogether, our results suggest that in routine laboratory practice, product-sizing analysis is globally similar to HRM for the detection of CALR mutations, and that both may be used as first-line screening tests. If the results are positive, Sanger sequencing can be used to confirm the mutation and to determine its type. Product-sizing analysis provides sensitive and specific results, moreover, with the quantitative measurement of CALR, which might be useful to monitor specific treatments. [ABSTRACT FROM AUTHOR]

The article discusses the Acute Leukemia French Association (ALFA)-0701 study which analyzes the positive impact of the level of blast CD33 expression to gemtuzumab ozogamicin (GO) in patients with acute myeloid leukemia. The in vitro result which shows the clear relationship between CD33 expression and GO efficacy and the evaluation of CD33 expression as a continuous covariable and highest response rates were reported for patients with CD33 expression in phase 2 study are mentioned.

Immune thrombocytopenla (ITP) Is art autoimmune disease with a complex pathogenesis. As in many B cell-related autoimmune diseases, rltuximab (RTX) has been shown to Increase platelet counts in some ITP patients. From an immunologic standpoint, the mode of action of RTX and the reasons underlying its limited efficacy have yet to be elucidated. Because spienectomy is a cornerstone treatment of 1TP, the immune effect of fIX on this major secondary iymphoid organ was investigated in 18 spleens removed from ITP patients who were treated or not with fIX. Spleens from ITP individuals had follicular hyperplasia consistent with secondary follicles. RTX therapy resulted in complete B.cell depletion In the blood and a significant reduction In splenic B cells, but these patients did not achieve remission. Moreover, whereas the percentage of circulating regulatory T cells (Tregs) was similar to that in controls, splenic Tregs were reduced in ITP patients. Interestingly, the ratio of prolnf lammatory Thi cells to suppressive Tregs was increased in the spleens of patients who failed RTX therapy. These results indicate that although B cells are involved In ITP pathogenesis, RTX-Induced total B-cell depletion is not correlated with its therapeutic effects, which suggests additional immune-mediated mechanisms of action of this drug. [ABSTRACT FROM AUTHOR]