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Monoclonal T-cell lymphocytosis has been reported in patients with concomitant autoimmune diseases, viral infections, or immunodeficiencies. Referred to as T-cell large granular lymphocytic leukemia (T-LGLL), most cases cannot identify the triggering cause. Only small case series have been reported in the literature, and no treatment consensus exists. T-cell lymphocytosis may also appear after the transplant of hematopoietic stem cells or solid organs. Rare cases have been reported in patients undergoing autologous stem cell transplant (ASCT) for hematological diseases (including multiple myeloma or non-Hodgkin’s lymphoma). Here, we describe the singular case of a patient who underwent ASCT for Hodgkin’s lymphoma and displayed the onset of T-LGLL with an uncommonly high number of lymphocytes in peripheral blood and their subsequent spontaneous remission. [ABSTRACT FROM AUTHOR]

Ruxolitinib is a JAK1/2 inhibitor that has revolutionized the approach to myelofibrosis. On the one side, this drug can rapidly improve the symptoms related to the hematological disease; on the other side, the inhibition of JAK1/2 can lead to immunosuppression which may increase the risk of infections, due to a change in the cytokine balance in favor of anti-inflammatory cytokines, to direct inhibition of immune cells, and to the suppression in the production of specific antibodies. In this patient setting, much is known about possible viral and bacterial infections, while little is reported in the literature concerning parasitic infections, specifically leishmaniasis. Leishmania is a parasitic infection that can cause serious problems in immunosuppressed patients. The parasite can invade the bloodstream and cause a wide range of symptoms, including fever, weight loss, and anemia. In severe cases, it can lead to multi-organ failure and, rapidly, death. Early diagnosis and prompt treatment are essential especially for these patients, unable to respond adequately. In this case and the following review of the existing literature, the cytokine kinetics and the production of specific anti-Leishmania antibodies represent characteristic aspects capable of providing a more in-depth understanding of the mechanisms underlying these complex clinical cases in an immunocompromised patient. [ABSTRACT FROM AUTHOR]

Abdominal ultrasound exams play a major role in the diagnosis of sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD). The development of portable hand-held ultrasound devices (HHUS) has been shown to facilitate the diagnosis of many diseases, but little data on the value of HHUS in the diagnosis of SOS/VOD are available. We performed a study aimed at validating portable ultrasound (US) devices in the setting of hematopoietic stem cell transplant (HCT). Sixteen evaluable patients undergoing allogeneic HCT were studied using conventional US and HHUS during the first 3 weeks after transplant. The results obtained demonstrate that there is a close correlation between conventional and handheld ultrasound examination in the measurement of the right hepatic lobe (r = 0.912, p < 0.0001), the left hepatic lobe (r = 0.843, p < 0.0001), the portal vein (PV) (r = 0.724, p < 0.0001), and the spleen (r = 0.983, p < 0.0001) based on Pearson's correlation. The same data, analyzed through Lin's concordance correlation coefficient, evidenced a substantial level of agreement in the comparison of the spleen and right hepatic lobe, while a lower grade of agreement in the measurement of the portal vein and left hepatic lobe. Moreover, there was good agreement between results obtained by the two types of ultrasound devices in assessing ascites (p < 0.0001), gallbladder thickening (p < 0.0001), and the direction of PV flow (p < 0.0001). HHUS device allows the study of HokUs-10 parameters with an excellent agreement with conventional US, and may contribute to SOS/VOD diagnosis. [ABSTRACT FROM AUTHOR]

Haematological patients represent a vulnerable population to opportunistic infections, mainly due to the disease itself and chemotherapy-induced neutropenia. The level of immune suppression strongly increases the importance of timely antibiotic treatment in order to prevent sepsis-related mortality. During the initial fever episode, serum biomarkers are usually used to estimate the probability of blood stream infection prior to the results of microbial diagnosis. A new serum biomarker combination study on a febrile haematological population, including C-reactive protein (CRP), interleukin-6 (IL−6) and procalcitonin (PCT), is proposed in order to improve their predictive accuracy. In our prospective study, CRP, IL−6 and PCT were evaluated in 34 immunosuppressed haematological patients immediately after the onset of 51 fever episodes, either during the course of standard chemotherapy or high-dose chemotherapy and autologous stem cell transplant. The fever episodes were divided into documented infections and fever alone. Receiver operating characteristic analysis (ROC) was performed for each biomarker and a combination of all three biomarkers (multiROC) to define a new predictive index. Significant differences were evidenced between the two groups (documented infection and no infection) for both PCT and IL−6 (p = 0.03 and p = 0.035, respectively), but none for CRP (p = 0.1). The composite parameter is more reliable than any single biomarker alone, with an area under the curve (AUC) of 79% and with high sensitivity and specificity. IL−6 gave the closest response compared to the composite index. Composite parameters of serum biomarkers could be used for an early diagnosis of infection at fever onset in haematological patients. [ABSTRACT FROM AUTHOR]

Assays of cytokines in the plasma at the onset of graft-vs. -host disease (GVHD) can predict disease severity and treatment-related mortality (TRM); however, the optimal time during which cytokines should be tested and the specific panel of cytokines with the highest predictive ability remain unknown. We chose a predefined time point, 18 days after hematopoietic stem cell transplantation (HSCT), to measure the levels of six cytokines in the plasma: soluble interleukin-2 receptor alpha (sIL2-Rα), T-cell immunoglobulin domain and mucin domain-3 (TIM-3), suppression of tumorigenicity-2 (ST-2), intercellular adhesion molecule (ICAM-1), interferon-gamma (IFN-γ), and interleukin-6 (IL-6). The study included 95 patients, who underwent allogeneic hematopoietic transplantation at our institution. Plasma levels of sIL2-Rα and TIM-3, measured as continuous data, had predictive value for overall survival (sIL2-Rα, p = 0.002; TIM-3, p = 0.0007), while TRM could be predicted by sIL2-Rα (p = 0.0005), IFN-gamma (p = 0.01), and IL-6 (p = 0.0001). No cytokine was associated with the risk of relapse. Patients were categorized into groups, according to cytokine thresholds determined by receiver operating characteristic curve analysis (sIL2-Rα ≤ or > 8,100 pg/ml; TIM-3 ≤ or > 950 pg/ml) and multivariate analysis was conducted. High levels of both TIM-3 and sIL2-Rα were significant predictors of poor survival [TIM-3 > 950 pg/ml: hazard ratio (HR) = 6.214 (95% CI 1.939–19.910), p = 0.002 and sIL2-Rα > 8.100 pg/ml: HR = 2.644 (95% CI 1.308–5.347), p = 0.006]. Using these cutoff thresholds, we constructed a composite scoring system that could distinguish three different groups of patients with varying rates of TRM: high risk, 41.7%; intermediate risk, 10.8%; and low risk, 7.1% (Gray's test: p = 0.001). If confirmed in a validation cohort, this composite scoring system could be used to guide the modulation of post-transplant immune suppressive therapy. [ABSTRACT FROM AUTHOR]

Endothelial dysfunction (ED) is frequently encountered in transplant medicine. ED is an argument of high complexity, and its understanding requires a wide spectrum of knowledge based on many fields of basic sciences such as molecular biology, immunology, and pathology. After hematopoietic stem cell transplantation (HSCT), ED participates in the pathogenesis of various complications such as sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD), graft-versus-host disease (GVHD), transplant-associated thrombotic microangiopathy (TA-TMA), idiopathic pneumonia syndrome (IPS), capillary leak syndrome (CLS), and engraftment syndrome (ES). In the first part of the present manuscript, we briefly review some biological aspects of factors involved in ED: adhesion molecules, cytokines, Toll-like receptors, complement, angiopoietin-1, angiopoietin-2, thrombomodulin, high-mobility group B-1 protein, nitric oxide, glycocalyx, coagulation cascade. In the second part, we review the abnormalities of these factors found in the ED complications associated with HSCT. In the third part, a review of agents used in the treatment of ED after HSCT is presented. [ABSTRACT FROM AUTHOR]

Allogeneic hematopoietic stem cell transplantation (HSCT) for high-risk acute myeloid leukemia (AML) represents the only curative option. Progress has been made in the last two decades in the pre-transplant induction therapies, supportive care, selection of donors and conditioning regimens that allowed to extend the HSCT to a larger number of patients, including those aged over 65 years and/or lacking an HLA-identical donor. Furthermore, improvements in the prophylaxis of the graft-versus-host disease and of infection have dramatically reduced transplant-related mortality. The relapse of AML remains the major reason for transplant failure affecting almost 40–50% of the patients. From 10 to 15 years ago to date, treatment options for AML relapsing after HSCT were limited to conventional cytotoxic chemotherapy and donor leukocyte infusions (DLI). Nowadays, novel agents and targeted therapies have enriched the therapeutic landscape. Moreover, very recently, the therapeutic landscape has been enriched by manipulated cellular products (CAR-T, CAR-CIK, CAR-NK). In light of these new perspectives, careful monitoring of minimal-residual disease (MRD) and prompt application of pre-emptive strategies in the post-transplant setting have become imperative. Herein, we review the current state of the art on monitoring, prevention and treatment of relapse of AML after HSCT with particular attention on novel agents and future directions. [ABSTRACT FROM AUTHOR]