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Severe haematological diseases and lymphoid malignancies require bone marrow (BM)-suppressive treatments. Knowledge regarding the impact of BM-suppressive treatments on children's memory T cells is very limited. Memory T cells play a crucial role in defending against herpesviruses, which is particularly relevant in paediatric cancer care. We studied 53 children in total; 34 with cancer and 2 with severe haematological disorders, with some receiving BM-suppressive treatment with or without allogeneic-haematopoietic stem cell transplantation (allo-HSCT), alongside 17 healthy controls. We focused on peripheral blood proportions of memory T-cell subsets using flow cytometry and analysed cytokine-secreting T cells with a four-parameter FluoroSpot assay in response to T-cell mitogen and varicella zoster virus (VZV) peptides. Patients on BM-suppressive treatment showed increased clusters of differentiation (CD)4+ and CD8+ effector memory (TEM)/terminally differentiated effector (TEFF) T cells compared to the healthy controls. They also exhibited, amongst other things, when compared to the healthy controls, a reduced total number of cytokine-secreting cells, by means of interferon (IFN)-γ, interleukin (IL)-17A, IL-10, and IL-22, following mitogen activation. A diminished IFN-γ response among the children with BM-suppressive treatment was observed upon VZV-peptide stimulation, compared to the healthy children. Collectively, the findings herein indicate that the children who are undergoing or have finished BM-suppressive treatment display qualitative differences in their T-cell memory compartment, potentially increasing their susceptibility to severe viral infections and impacting their immunotherapy, which relies on the functional ability of autologous T cells.

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Papillary thyroid cancer (PTC) is the most common endocrine malignancy. 10% to 15% of individuals show familial clustering with three or more affected members, but the factors underlying this risk are unknown. In a group of recently studied individuals with POT1 pathogenic variants and ultra-long telomere length, PTC was the second most common solid tumor. We tested whether variants in POT1 and four other telomere-maintenance genes associated with familial cancer underlie PTC susceptibility. Among 470 individuals, we identified pathogenic or likely pathogenic variants in three genes encoding telomere-binding proteins: POT1, TINF2, and ACD. They were found in 4.5% and 1.5% of familial and unselected cases, respectively. Individuals harboring these variants had ultra-long telomere length, and 15 of 18 (83%) developed other cancers, of which melanoma, lymphoma, and sarcoma were most common. Among individuals with PTC and melanoma, 22% carried a deleterious germline variant, suggesting that a long telomere syndrome might be clinically recognizable. Successive generations had longer telomere length than their parents and, at times, developed more cancers at younger ages. Tumor sequencing identified a single oncogenic driver, BRAF p.Val600Glu, in 10 of 10 tumors studied, but no telomere-maintenance mechanism, including at the TERT promoter. These data identify a syndromic subset of PTCs with locus heterogeneity and telomere lengthening as a convergent mechanism. They suggest these germline variants lower the threshold to cancer by obviating the need for an acquired telomere-maintenance mechanism in addition to sustaining the longevity of oncogenic mutations.

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BACKGROUND: Venous thromboembolism (VTE) is a cause of increased morbidity and mortality in cancer patients. VTE is the second leading cause of death in cancer patients. Risk assessment models have been developed to identify patients at risk of VTE for thromboprophylaxis. Risk scores of patients in our environment have not been adequately investigated. OBJECTIVE: The study evaluates the association of thrombotic risk assessment scores (using the modified Khorana risk assessment tool) and soluble P-selectin levels with thrombotic events in patients with lymphoid cancer. METHODS: This is a comparative cross-sectional study conducted at Nnamdi Azikiwe University Teaching Hospital (NAUTH, Nnewi, Anambra State). Forty-five patients with lymphoid malignancy and 45 apparently healthy subjects participated in the study. The modified Khorana risk assessment score was used to assess cancer-associated thrombotic risk. Blood sample was collected for soluble P-selectin estimation. Data were analyzed with SPSS version 23. RESULTS: The age of subjects with lymphoid neoplasm and controls were 49.1±15.8 years, and 49.6±11.1 years respectively (p = 0.548). Subjects with lymphoid neoplasm consist of 26 (57.8%) males and 19 (42.2%) females while the controls consist of 25 (55.6%) males and 20 (44.4%) females. Non-Hodgkin's lymphoma was the most frequent of lymphoid neoplasm (18, 40.0%), followed by multiple myeloma (10, 22%), CLL (9, 20%), ALL (6, 13.0%) and Hodgkin's lymphoma (2, 4.0%). Thirty-five (77.8%) subjects with lymphoid neoplasm had intermediate risk scores and 10 (22.2%) had high-risk scores. Nineteen (42.2%) of the controls had intermediate risk and 26 (57.8%) low risk. The differences in proportion were statistically significant (p < 0.001). The median (IQR) levels of soluble P-selectin were significantly higher in patients with lymphoid neoplasm (12.2 vs. 7.0ng/mL, p <0.001). Three (6.6%) patients with lymphoid malignancies had deep vein thrombosis confirmed by a Doppler ultrasound scan. CONCLUSION: Lymphoid malignancy is associated with relatively higher thrombotic risk scores, sP-selectin levels, and venous thromboembolic events. CONTEXTE: La thromboembolie veineuse (TEV) est une cause de morbidité et de mortalité accrues chez les patients atteints de cancer. La TEV est la deuxième cause de décès chez les patients atteints de cancer. Des modèles d'évaluation des risques ont été mis au point pour identifier les patients présentant un risque de TEV en vue d'une thromboprophylaxie. Les scores de risque des patients dans notre environnement n'ont pas été étudiés de manière adéquate. OBJECTIF: L'étude évalue l'association des scores d'évaluation du risque thrombotique (en utilisant l'outil modifié d'évaluation du risque de Khorana) et des niveaux de P-sélectine soluble avec les événements thrombotiques chez les patients atteints d'un cancer lymphoïde. MÉTHODES: Il s'agit d'une étude transversale comparative menée au Nnamdi Azikiwe University Teaching Hospital (NAUTH, Nnewi, État d'Anambra). Quarante-cinq patients atteints d'un cancer lymphoïde et 45 sujets apparemment sains ont participé à l'étude. Le score modifié d'évaluation du risque de Khorana a été utilisé pour évaluer le risque thrombotique associé au cancer. Un échantillon de sang a été prélevé pour l'estimation de la P-sélectine soluble. Les données ont été analysées avec SPSS version 23. RÉSULTATS: L'âge des sujets atteints de néoplasme lymphoïde et des témoins était respectivement de 49,1±15,8 ans et 49,6±11,1 ans (p = 0,548). Les sujets atteints de néoplasme lymphoïde sont 26 (57,8 %) hommes et 19 (42,2 %) femmes, tandis que les témoins sont 25 (55,6 %) hommes et 20 (44,4 %) femmes. Le lymphome non hodgkinien était le néoplasme lymphoïde le plus fréquent (18, 40 %), suivi du myélome multiple (10, 22 %), de la LLC (9, 20 %), de la LAL (6, 13 %) et du lymphome hodgkinien (2, 4 %). Trente-cinq (77,8 %) sujets atteints de néoplasmes lymphoïdes présentaient un score de risque intermédiaire et 10 (22,2 %) un score de risque élevé. Dix-neuf (42,2 %) des témoins présentaient un risque intermédiaire et 26 (57,8 %) un risque faible. Les différences de proportion étaient statistiquement significatives (p < 0,001). Les niveaux médians (IQR) de P-sélectine soluble étaient significativement plus élevés chez les patients atteints de néoplasme lymphoïde (12,2 vs. 7,0 ng/mL, p <0,001). Trois (6,6 %) patients atteints de tumeurs lymphoïdes ont présenté une thrombose veineuse profonde confirmée par une échographie Doppler. CONCLUSION: Les tumeurs malignes lymphoïdes sont associées à des scores de risque thrombotique, des taux de sP-sélectine et des événements thromboemboliques veineux relativement plus élevés. Mots-clés: Malignité lymphoïde, Thrombose, P-sélectine soluble, Scores d'évaluation du risqué.

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Vaccines having aided in escaping the majority of the population from immunological naïvety, our strategies are now shifting towards an increased focus on identifying and protecting the extremely vulnerable. We here describe the results of testing 12 patients, those with lymphoid malignancies having been targeted their B-cells for therapy with rituximab-containing regimens or a Bruton tyrosine kinase inhibitor, for anti-SARS-CoV-2 spike antibodies after receiving the BNT162b2 mRNA vaccine doses. The interval from last dosing of B-cell depletion therapy to SARS-CoV-2 vaccination was at median 5.3 (range 3.1-6.6) months. Using the 'seroprotection' threshold of 775 [BAU/mL] for the anti-spike antibody titer, our finding points out the crucial unresponsiveness of the targeted population with 0/12 (0%) achieving 'seroprotection'. Although IgG seroconversion was observed in 4/12 (33%), supporting the overall benefit of vaccination, the figures still point out a potential need for optimization of practice. IgA was further less responsive (unsuccessful 'seroconversion' in 11/12 (92%)), implicating an underlying class switch defect. Those with depletion on B-cells are caught at a dilemma between, being too early and too late on receiving SARS-CoV-2 vaccines. They wish to get over their immunological naïvety at the earliest, while, in order to assure quality immune memory, are also required to hold the patience for their B-cells to repopulate. Although it remains an issue whether intensified vaccine schedules and/or regimens will lead to stronger immunogenicity or more effective boosters for non-responders, we shall take advantage of every increasing evidence in order to optimize current options.

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Chimeric antigen receptor (CAR) T-cell therapy has emerged recently as a standard of care treatment for patients with relapsed or refractory acute lymphoblastic leukemia (ALL) and several subtypes of B-cell non-Hodgkin lymphoma (NHL). However, its use remains limited to highly specialized centers, given the complexity of its administration and its associated toxicities. We previously reported our experience in using a novel Sleeping Beauty (SB) CD19-specific CAR T-cell therapy in the peri-transplant setting, where it exhibited an excellent safety profile with encouraging survival outcomes. We have since modified the SB CD19 CAR construct to improve its efficacy and shorten its manufacturing time. We report here the phase 1 clinical trial safety results. Fourteen heavily treated patients with relapsed/refractory ALL and NHL were infused. Overall, no serious adverse events were directly attributed to the study treatment. Three patients developed grades 1-2 cytokine release syndrome and none of the study patients experienced neurotoxicity. All dose levels were well tolerated and no dose-limiting toxicities were reported. For efficacy, 3 of 8 (38%) patients with ALL achieved CR/CRi (complete remission with incomplete count recovery) and 1 (13%) patient had sustained molecular disease positivity. Of the 4 patients with DLBCL, 2 (50%) achieved CR. The SB-based CAR constructs allow manufacturing of targeted CAR T-cell therapies that are safe, cost-effective and with encouraging antitumor activity.

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Patients with lymphoid malignancies are at a higher risk of coronavirus disease 2019 (COVID-19) infection due to their immunocompromised state and results in higher mortality rates in these patients. Anti-CD 20 therapy is one of the leading causes of immunosuppression that worsens in COVID-19 cases. COVID-19 vaccines, on the other hand, appear to be less beneficial to these patients. App-ropriate treatment and recommendations are required for these COVID-19 patients with lymphoid malignancies.

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BACKGROUND: The majority of patients with large B-cell lymphoma treated with axicabtagene ciloleucel (axi-cel), an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, develop cytokine release syndrome (CRS). Whether the lack of development of CRS with axi-cel is associated with inferior lymphoma outcomes is unknown. Additionally, relationship between CRS grade and lymphoma outcome is not well established. METHODS: The US Lymphoma CAR T Consortium includes seventeen US academic centers that contribute data independently of manufacturers. We analyzed the modified intent-to-treat population of 275 patients receiving axi-cel in two different ways: 1) Two group analysis comparing no CRS with any grade CRS; 2) Three group analysis comparing grade 0 CRS with grade 1 to 2 CRS, and grade 3-5 CRS. RESULTS: In this large multi-center observational cohort of 275 patients receiving axi-cel, 9% (n = 24) did not develop CRS, 84% (n = 232) developed grade 1-2 CRS, and 7% (n = 19) developed grade 3 to 5 CRS. Patients without CRS, compared with those having any grade CRS, had similar overall response rates (ORR), lower complete response (CR) rates and inferior progression free survival (PFS) with no statistically significant difference in overall survival (OS). Patients experiencing grade 1 to 2 CRS had superior CR rate and PFS, as compared to those without CRS or with grade 3 to 5 CRS. Grade 3 to 5 CRS was associated with a worse OS. CONCLUSION: Overall, durable responses were seen in patients that did not develop CRS, however grade 1 to 2 CRS was associated with better outcomes while those with grade 3 to 5 experienced the worse outcomes.

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I will have a couple of comments on the issues elaborated in the article titled as 'Impact of COVID-19 in patients with lymphoid malignancies'. First, the author did not emphasize and overlook the prolonged persistence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in coronavirus disease 2019 (COVID-19) patients with hematological malignancies. Second, the rise of a chronic lymphoid leukemia clone in COVID-19 was not mentioned by the authors. Third, achieving a complete remission in asymptomatic COVID-19 patients with follicular lymphoma in partial remission after bendamustine-based therapy is not specific to this lymphoma subtype. Fourth, follicular lymphoma does not always undergo complete remission with SARS-CoV-2 infection. Our aim is to help the authors to discuss and clarify these issues a little more in COVID-19 patients with hematological malignancies.

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It is widely accepted that the tumor microenvironment plays an important role in the progression of lymphoid malignancies. Interaction between the tumor and its surrounding immune cells is considered a potential therapeutic target. For example, anti-programmed cell death 1 (PD-1) antibody stimulates the surrounding exhausted immune cells to release PD-1/PD-L1, thereby leading to the regression of PD-L1-positive tumors. Recently, biological phenomena, such as trogocytosis and exosome-mediated transport were demonstrated to be involved in establishing and maintaining the tumor microenvironment. We found that trogocytosis-mediated PD-L1/L2 transfer from tumor cells to monocytes/macrophages is involved in immune dysfunction in classic Hodgkin lymphoma. Exosomes derived from Epstein-Barr virus (EBV)-associated lymphoma cells induce lymphoma tumorigenesis by transferring the EBV-coding microRNAs from the infected cells to macrophages. In this review, we summarized these biological phenomena based on our findings.

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The cytokine interleukin-7 (IL-7) and its receptor are critical for lymphoid cell development. The loss of IL-7 signaling causes severe combined immunodeficiency, whereas gain-of-function alterations in the pathway contribute to malignant transformation of lymphocytes. Binding of IL-7 to the IL-7 receptor results in the activation of the JAK-STAT, PI3K-AKT and Ras-MAPK pathways, each contributing to survival, cell cycle progression, proliferation and differentiation. Here, we discuss the role of deregulated IL-7 signaling in lymphoid malignancies of B- and T-cell origin. Especially in T-cell leukemia, more specifically in T-cell acute lymphoblastic leukemia and T-cell prolymphocytic leukemia, a high frequency of mutations in components of the IL-7 signaling pathway are found, including alterations in IL7R, IL2RG, JAK1, JAK3, STAT5B, PTPN2, PTPRC and DNM2 genes.

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BACKGROUND: In the present systematic literature review, we sought to describe the burden and treatment practices of adult acute lymphoblastic leukemia (ALL) in India, which reflect the realities and outcomes in a middle-income country. MATERIALS AND METHODS: We conducted a search for reported studies using terms such as "adult ALL," "epidemiology," and "treatment" in the Medline, Embase, Cochrane, and other database sources. We obtained 249 articles and 18 conference abstracts reported until December 2019. A total of 40 studies were selected to qualitatively summarize the data. RESULTS: The proportion of ALL among adult patients diagnosed with acute leukemia at reporting institutions from 16 Indian studies ranged from 7.3% to 57.8%. Most studies were performed in Northern India (n = 12), had a male preponderance (range, 57%-80%), and had a predominance of B-ALL (range, 65.2%-75.9%). The treatment protocols used for ALL included MCP-841, BFM (Berlin-Frankfurt-Münster)-90, chemotherapy plus a tyrosine kinase inhibitor, GMALL (German Multicenter Study Group for Adult Acute Lymphoblastic Leukemia), and hyper-CVAD (cyclophosphamide, vincristine, doxorubicin, dexamethasone). The complete remission rates and median overall survival for these protocols ranged from 46.7% to 91.4% and 7 to 46 months, respectively. The overall relapse rates were 24.3% to 57.1% within median time of 9 to 24 months, with bone marrow the most frequent relapse site. After relapse, most patients had chosen palliative therapy (range, 78.7%-96.0%). The major treatment-related toxicities included neutropenia, myelosuppression, and infection. CONCLUSIONS: The results from Indian studies on adult ALL are heterogeneous, reporting a diverse incidence and poor overall outcomes using varied non-contemporaneous treatment protocols adapted from the developed world. A comprehensive countrywide approach to diagnosis, treatment, and follow-up and the potential incorporation of novel therapies could improve the prognosis and outcomes of adult ALL in India.

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BACKGROUND AND AIMS: Hyperglycemia and glucose test abnormalities are problems during the treatment of patients with lymphoid malignancy, caused by corticosteroid therapy. However, its long-term complications or risk of developing diabetes are not available. METHODS: Two hundred patients with lymphoid hematologic malignancy were recruited and followed up for median of 47 months. The underlying hematologic malignancy includes Hodgkin's disease (HD), Non-Hodgkin's Lymphoma (NHL), Chronic Lymphocytic Leukemia(CLL), Multiple Myeloma (MM) and Acute Lymphocytic Leukemia (ALL). Fasting blood sugar, glucose tolerance test and lipid profiles were measured before each chemotherapy cycle and every 3 months after. This study was designed to evaluate patients for long-term follow up of glucose tests abnormalities. RESULTS: The mean age of the non-diabetic patients was significantly lower than that of diabetics and patients with fasting glucose disorder (p < 0.001). The prevalence of diabetes and impaired FBS and GTT was higher in NHL (9%), CLL (6.5%) and MM (1.5%), respectively. For lipid profiles, the highest levels of cholesterol and triglycerides were observed in multiple myeloma and the lowest in Hodgkin's lymphoma (P:0.004). CONCLUSIONS: The most important factor for steroid-induced diabetes is age, which was more prevalent with age increase (P < 0.001). Glucocorticoid-induced diabetes is common in multiple myeloma and then in chronic lymphocytic leukemia and non-Hodgkin's lymphoma in comparison with Hodgkin's lymphoma and acute lymphoblastic leukemia.

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OBJECTIVES: To investigate concordance in survival time among first-degree relatives with lymphoid malignancies. METHODS: By linkage of national Swedish registers, we identified 66 430 patients diagnosed with a lymphoid malignancy 1958-2016 with information on first-degree relationships and follow-up until 2017. Among these, we identified pairs of first-degree relatives with any (N = 3326) or a similar (N = 690) lymphoid malignancy subtype. We defined survival in the first-degree relative as good, expected, or poor based on tertiles of deviance residuals from a multivariable Cox regression model. Next, we used Cox regression to estimate hazard ratios (HR) of death with 95% confidence intervals (CI) among patients, using the survival of their first-degree relative as exposure and adjusting for confounders. RESULTS: There was no concordance in survival among first-degree relatives with any lymphoid malignancy (HRgood  = 1.00 (reference), HRExpected  = 1.02, 95% CI: 0.89-1.17, HRPoor  = 1.12, 95% CI: 0.98-1.27, Ptrend  = .08). Among first-degree relatives with indolent lymphoma, including chronic lymphocytic leukemia, those with a first-degree relative to an expected or poor survival had worse outcome compared to those with a first-degree relative with good survival (HRExpected  = 1.44, 95% CI: 0.82-2.53, HRPoor  = 1.79, 95% CI: 1.07-3.00, Ptrend  = .03). CONCLUSION: Our results support a role of inherited factors in the outcome of indolent lymphoma, including chronic lymphocytic leukemia.

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Glucocorticoids are one of the key drugs used in palliative therapy. They have several palliative effects. However, aside from these effects, glucocorticoids have anti-tumor effects on lymphoid malignancies. In particular, for patients with lymphoid malignancy in the terminal stage of the disease, this medical modality can produce both symptomatic relief and anti-tumor effects without serious side effects. This article presents two impressive cases of patients with terminal lymphoid malignancy treated with glucocorticoids, who showed survival advantages and improved quality of life.

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PURPOSE: Globally, cancer is a critical illness which seriously threatens human health. T-cell-based cancer immunotherapy for some patients has demonstrated impressive achievements including chimeric antigen receptor T cells, immune checkpoint inhibitors and T cell-redirecting bispecific antibodies (TRBAs). TRBAs recruit T cells to lyse cancer cells bypassing the antigen presentation through the major histocompatibility complex pathways. In this review we summarized the TRBAs formats, biophysical characteristics, the preclinical and clinical trial results, as well as the challenges faced by TRBAs in tumour therapy. METHODS: Herein the relevant literature and clinical trials from the PubMed and ClinicalTrials.gov database. RESULTS: The advances in protein engineering technology have generated diverse TRBAs format which can be classified into two categories: IgG-like TRBAs and non-IgG-like TRBAs. Multiple applications of TRBAs showed encouraging curative effect and entered clinical trials for lymphoid malignancy and solid tumour. CONCLUSIONS: TRBA is a powerful tool for the cancer treatment and the clinical studies showed potent anti-tumour efficacy in hematologic malignancies. Although the clinical outcomes of TRBAs in solid tumours are less satisfied than hematologic malignancies, many preclinical antibodies and combination therapies are being evaluated.

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BACKGROUND: Extranodal natural killer/T-cell lymphoma (ENKTL) is a rare lymphoid malignancy with diverse clinical features and prognoses. The aims of this study were to explore the pretreatment prognostic factors of ENKTL and develop a new individual prognostic model. PATIENTS AND METHODS: We retrospectively enrolled 81 ENKTL patients with newly diagnosed disease between June 2006 and August 2017 at the Affiliated Cancer Hospital of Guangxi Medical University. Survival analysis was used to assess the prognostic value of various factors. A nomogram was developed to predict overall survival (OS) based on the Cox proportional hazards model. RESULTS: The median survival time of the patients was 48 months, and the 5-year OS rate was 47.5%. Cox regression analysis showed that the prognostic factors of OS for ENKTL patients included Eastern Cooperative Oncology Group performance status, Ann Arbor stage, pretreatment albumin-to-globulin ratio, and platelet count. A prognostic nomogram was developed to predict the OS rate for ENKTL patients based on these factors. The calibration curve showed that the nomogram was able to predict OS accurately. The concordance index of the nomogram for OS prediction was 0.807. CONCLUSION: Our proposed nomogram based on Eastern Cooperative Oncology Group performance status, Ann Arbor stage, albumin-to-globulin ratio, and platelet count provides an individualized risk estimate of OS in patients with ENKTL.

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The role of HLA system in allogeneic haematopoietic stem cell transplantation (allo-HSCT) outcome is unarguable. In this study we investigated association of HLA-A,-B and-DRB1 alleles with overall survival (OS) in 186 patients undergoing allo-HSCT for lymphoid malignancies. Analyses confirmed significantly better OS for HLA-DRB1∗04 carriers compared with non-carriers (p = 0.01). Survival benefit was confined to male patients (in multivariate analyses p = 0.034, hazard ratio 0.35, 95% confidence interval 0.13-0.92), whereas in females no difference was noted (p = 0.82). Furthermore, donor gender also affected outcome and transplantation from female HLA-DRB1∗04 carrier donors resulted in superior survival compared with female non-carrier donors (p = 0.01). Combined analyses including recipient/donor gender and HLA-DRB1∗04 showed that survival of male patients varied significantly according to donor gender and HLA-DRB1∗04 carriership (p = 0.04) with best survival among HLA-DRB1∗04 carriers transplanted from female donors. Of relevance to our results, HLA-DRB1∗04 has been documented as risk allele group for lymphoid malignancies, and studies described a male-specific risk. We believe that our findings provide further supporting evidence for sex-specific alterations secondary to HLA-DRB1∗04 or related genes. Further studies are warranted to evaluate whether in contrast to general favour of male donors HLA-DRB1∗04 carrier patients with lymphoid malignancies could benefit from transplantation from female donors.

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Acute lymphocytic leukemia (ALL) is uncommon lymphoid malignancy in dogs, and its diagnosis is challenging. A 14-year-old spayed female mixed breed dog was transferred to a veterinary medical teaching hospital for an immediate blood transfusion. The dog showed lethargy, pale mucous membranes, and a weak femoral pulse. Complete blood count revealed non-regenerative anemia and severe leukopenia with thrombocytopenia. ALL was tentatively diagnosed based on the predominance of immature lymphoblasts on blood film examination. For confirmation of lymphoid malignancy, PCR for antigen receptor rearrangement (PARR) on a peripheral blood sample and flow cytometry analysis were performed after blood transfusion. Flow cytometry analysis revealed that lymphocyte subsets were of normal composition, but PARR detected a T-cell malignancy. The dog was diagnosed with ALL and survived 1 wk after diagnosis. In conclusion, after blood transfusion, flow cytometry was not a reliable diagnostic method for an ALL dog, whereas PARR could detect lymphoid malignancy. Our results suggest that PARR should be the first-line diagnostic tool to detect canine lymphoid malignancy after a blood transfusion.

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The phagocytic clearance of host cells is important for eliminating dying cells and for the therapeutic clearance of antibody-targeted cells. As ubiquitous, motile and highly phagocytic immune cells, macrophages are principal players in the phagocytic removal of host cells throughout the body. In recent years, great strides have been made in identifying the molecular mechanisms that control the recognition and phagocytosis of cells by macrophages. However, much less is known about the physical and metabolic constraints that govern the amount of cellular material macrophages can ingest and how these limitations affect the overall efficiency of host cell clearance in health and disease. In this review we will discuss, in the contexts of apoptotic cells and antibody-targeted malignant cells, how physical and metabolic factors associated with the internalization of host cells are relayed to the phagocytic machinery and how these signals can impact the overall efficiency of cell clearance. We also discuss how this information can be leveraged to increase cell clearance for beneficial therapeutic outcomes.

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