CD146 Molecule Expression in B Cells Acute Lymphoblastic Leukemia (B-ALLs): A Flow-Cytometric Marker for an Accurate Diagnostic Workup.

Background: B-lineage acute lymphoblastic leukemias (B-ALL) harboring the t(9;22)(q34;q11)/BCR::ABL1 rearrangement represent a category with previously dismal prognosis whose management and outcome dramatically changed thanks to the use of tyrosine kinase inhibitors (TKIs) usage and more recently full chemo-free approaches. The prompt identification of these cases represents an important clinical need. Objectives: We sought to identify an optimized cytofluorimetric diagnostic panel to predict the presence of Philadelphia chromosome (Ph) in B-ALL cases by the introduction of CD146 in our multiparametric flow cytometry (MFC) panels. Methods: We prospectively evaluated a total of 245 cases of newly diagnosed B-ALLs with a CD146 positivity threshold >10% referred to the Division of Hematology of 'Sapienza' University of Rome. We compared the results of CD146 expression percentage and its mean fluorescence intensity (MFI) between Ph+ ALLs, Ph-like ALLs, and molecularly negative ALLs. Results: Seventy-nine of the 245 B-ALL cases (32%) did not present mutations at molecular testing, with 144/245 (59%) resulting in Ph+ ALL and 19/245 (8%) Ph-like ALLs. Comparing the 3 groups, we found that Ph+ B-ALLs were characterized by higher expression percentage of myeloid markers such as CD13, CD33, and CD66c and low expression of CD38; Ph+ B-ALL showed a higher CD146 expression percentage and MFI when compared with both molecular negative B-ALL and Ph-like ALLs; neither the mean percentage of CD146 expression neither CD146 MFI were statically different between molecular negative B-ALL and Ph-like ALLs. Conclusions: Our data demonstrate the association between CD146 expression and Ph+ ALLs. CD146, along with myeloid markers, may help to identify a distinctive immunophenotypic pattern, useful for rapid identification in the diagnostic routine of this subtype of B-ALLs that benefits from a specific therapeutic approach.

True vs. false immune-mediated thrombotic thrombocytopenic purpura exacerbations: a clinical case in the caplacizumab era.

Acquired thrombotic thrombocytopenic purpura (aTTP) is a medical emergency requiring urgent plasma exchange and immunosuppressive agents. Recently, the therapeutic options have been expanded by the approval of a novel anti-von Willebrand factor (vWF) nanobody, caplacizumab, inhibiting vWF-platelet aggregation. Here, we present a rare case of a patient affected by immune-mediated TTP (iTTP) reporting ischemic stroke caused by a real iTTP exacerbation during caplacizumab administration and subsequent pancytopenia caused by cytomegalovirus (CMV) infection that mimicked another iTTP exacerbation. The case is a real-life example of a not-frequent iTTP exacerbation in the caplacizumab era and of the new management issues arising with the introduction of the new drugs in clinical practice, highlighting the need of new comprehensive response criteria and treatment guidelines.

A Non-Destructive Methodology for the Viscoelastic Characterization of Polymers: Toward the Identification of the Time-Temperature Superposition Shift Law.

Polymers find widespread applications in various industries, such as civil engineering, aerospace, and industrial machinery, contributing to vibration control, dampening, and insulation. To accurately design products that are able to predict their dynamic behavior in the virtual environment, it is essential to understand and reproduce their viscoelastic properties via material physical modeling. While Dynamic Mechanical Analysis (DMA) has traditionally been used, innovative non-destructive techniques are emerging for characterizing components and monitoring their performance without deconstructing them. In this context, the Time-Temperature Superposition Principle (TTSP) represents a powerful empirical procedure to extend a polymer's viscoelastic behavior across a wider frequency range. This study focuses on replicating an indentation test on viscoelastic materials using the non-destructive Viscoelasticity Evaluation System evolved (VESevo) tool. The primary objective is to derive a unique temperature-frequency relationship, referred to as a "shift law", using characteristic curves from this non-invasive approach. Encouragingly, modifying the device setup enabled us to replicate, virtually, three tests under identical initial conditions but with varying indentation frequencies. This highlights the tool's ability to conduct material testing across a range of frequencies. These findings set the stage for our upcoming experiment campaign, aiming to create an innovative shift algorithm from at least three distinct master curves at specific frequencies, offering a significant breakthrough in non-destructive polymer characterization with broad industrial potential.

Correspondence in reference to the previously published manuscript: Reduction of cycles of bendamustine plus rituximab therapy in the cases with good response for indolent B-cell lymphomas.

Takezaki et al. analyzed the outcome of 57 patients with indolent lymphomas treated with Bendamustine plus Rituximab (BR) according to the number of cycles received, showing that patients who discontinued BR after four cycles had similar outcomes compared to patients who received five or six cycles. Considering the similarities but also the differences between indolent lymphomas and chronic lymphocytic leukemia (CLL), we enriched the results obtained with a cohort of CLL patients treated with BR starting from the experience of the Lazio region group on CLL. Out of 115 patients, 97 (84%) received 4-6 cycles of BR, while 18 (16%) received 1-3 cycles. The outcome of the group of patients who received at least 4 cycles was superior in terms of response rate (ORR 96% vs. ORR 83%, p = 0.041; CR 58% vs. CR 28%, p = 0.052 respectively) and PFS [median PFS 52.6 (40.3-64.9) versus 26.2 (19.3-33.0) months, p < 0.001]. The number of patients undergoing 4 cycles of BR (4-cycles group) and 5-6 cycles (over-4-cycles group) was 9 and 88, respectively. Compared to analysis conducted by the Japanese group in indolent lymphomas, in CLL we did not observe any difference between the outcome of the 4-cycles group and the over-4-cycles group in terms of ORR (89% vs. 97%, p = 0.268) and in survival [median PFS 40.8 (13.7-67.8) versus 52.6 (38.7-66.5) months, p = 0.117]. Moreover, we observed that patients who achieved a clinical CR showed overlapping outcomes with patients who received more than 4 cycles [CR vs. non-CR median PFS not reached vs. 11.0 months; over-4-cycles group median PFS 52.6 months (40.3-64.9); p < 0.001]. Nowadays chemoimmunotherapy with BR is reserved to fit elderly CLL patients, and there are many chemo-free treatment options available; therefore, discontinuation after 4 cycles may be permissible in patients who obtained a CR in order to limit toxicity as much as possible.