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OBJECTIVE: Essential thrombocythaemia (ET) is a myeloproliferative neoplasm in which there is an increased risk of thrombotic complications. The conventional thrombosis risk assessment of these patients is based on an age over 60 and a history of thrombosis. The aim of this report is to analyse the contribution of cardiovascular risk (CV) factors as possible additional thrombotic risk factors in the thrombotic complications seen in ET. PATIENTS AND METHODS: One hundred and one ET patients (72 females and 29 males with a median age of 61 years) were enrolled between 1999 and 2011. Mann-Whitney and multivariate binary logistic regression tests were performed. The Kaplan-Meier method followed by the log-rank test was used to evaluate the probability of thrombosis-free survival. RESULTS: The presence of one or two or more CV risk factors significantly increased the risk of thrombosis. Separately, the contribution of high blood pressure and hyperlipidaemia proved to be influential, whereas tobacco use, diabetes mellitus and obesity were not significant. Significant differences were revealed in the probability of thrombosis-free survival between patients without CV risk factors and those with at least one CV risk factor, and between those with at most one CV risk factor and those with two or more CV risk factors. CONCLUSIONS: On the basis of the results on the current cohort, it is suggested that CV risk factors may influence the thrombotic complications in ET. [ABSTRACT FROM AUTHOR]

OBJECTIVE: In polycythaemia vera (PV) and essential thrombocythaemia (ET), the life expectancy of the patients is greatly affected by thrombotic events. An investigation was performed of the potential association of PV/ET, and thrombotic complications with cardiovascular (CV) risk factors, a leukocyte count at the haematological diagnosis > 11.1 G/L, and the JAK2V617F mutation. PATIENTS AND METHODS: In the period 1998-2011, 128 women with a median age of 62 years were enrolled. RESULTS: The risk of thrombotic events before the diagnosis was 32.8% (42/128), while in the follow-up period it was 10.2% (13/128).The difference in the probability of thrombosis-free survival between those with at most one CV risk factor and those with two or more CV risk factors was significant (p = 0.005). The presence of two or more CV risk factors (univariate: p = 0.011; multivariate: relative risk: 4.728, 95% CI 1.312-17.040; p = 0.018) significantly increased the risk of thrombosis. Univariate analyses revealed that high blood pressure (p = 0.001), hyperlipidaemia (p = 0.005) and cigarette smoking (p = 0.051) were associated with a significantly higher risk of thrombosis. Analyses of the influence of the leukocyte count (univariate: p = 0.424; multivariate: relative risk: 1.407, 95% CI 0.359-5.507; p = 0.624) and the JAK2V617F mutation (univariate: p = 0.367; multivariate: relative risk: 1.428, 95% CI 0.316-6.460; p = 0.643) on subsequent thrombotic complications resulted in a non-signicant tendency. CONCLUSIONS: Female patients who display CV risk factors (high blood pressure, hyperlipidaemia and/or cigarette smoking) and PV or ET may well be at a higher risk of thrombotic events and require special consideration as concerns as the prevention and management of thrombotic events. [ABSTRACT FROM AUTHOR]

From a dermatological aspect, it posed a considerable challenge the skin-limited form of mastocytosis, urticaria pigmentosa and indolent systemic mastocytosis (ISM) with cutaneous lesions. Despite the favourable prognosis, lifelong dermatological control is needed, during which the average symptomatic therapy does not always seem adequate. We report here the case of a female ISM patient with recurrent cutaneous symptoms that impaired her quality of life, with a follow-up time of 27 years. During this long follow-up period, the cutaneous lesions could be controlled by antihistamines, leukotriene antagonists, glucocorticoids, local immunosuppressants or local UV radiation for only relatively short periods. Imatinib mesylate was, therefore, introduced in an attempt to control the cutaneous lesions. Tyrosine kinase inhibition is an unusual dermatological therapeutic option. This case illustrates that imatinib mesylate was a good choice with which to achieve a reduction of the skin lesions in this KIT D816V mutation-negative disease: it led to a temporary appreciable improvement of the patient's quality of life. [ABSTRACT FROM AUTHOR]

Aim: To investigate the diagnostic role of the 18F-FDG PET in the detection of residual tumour in Hodgkin disease. Material and methods: In the last decade in Hodgkin disease patients following the primary therapy CT investigation revealed residual disease in 73 cases. 18F-FDG PET investigations were performed for restaging in all of these patients. Results: 18F-FDG PET revealed active disease in 28 patients. Twenty-one of these patients had activity sings. In 5 of the patients complete remission was found after second-line therapy, and progressive disease was diagnosed in 16 cases. The other 7 patients did not have other activity signs, all of these patient are in stabile state. 18F-FDG PET was negative in 45 patients. In 2 of these cases recurrent disease was diagnosed in the first year. The other 43 patients did not showed activity signs. Conclusion: Negative 18F-FDG PET result is a good prognostic sign in Hodgkin disease patients for the disease free survival after the first-line therapy. Positive 18F-FDG PET finding with other activity signs indicates second-line therapy. Other investigations are required to clarify the cause of the relative high rate of 18F-FDG positive cases, in whom second line therapy was unnecessary. [ABSTRACT FROM AUTHOR]

TP53 aberrations predict chemoresistance and represent a contraindication for the use of standard chemoimmunotherapy in chronic lymphocytic leukaemia (CLL). Recent next-generation sequencing (NGS)-based studies have identified frequent low-burden TP53 mutations with variant allele frequencies below 10%, but the clinical impact of these low-burden TP53 mutations is still a matter of debate. In this study, we aimed to scrutinise the subclonal architecture and clinical impact of TP53 mutations using a sensitive, NGS-based mutation analysis in a 'real-world' cohort of 901 patients with CLL. In total, 225 TP53 mutations were identified in 17.5% (158/901) of the patients; 48% of these alterations represented high-burden mutations, while 52% were low-burden TP53 mutations. Low-burden mutations as sole alterations were identified in 39% (62/158) of all mutated cases with 82% (51/62) of these being represented by a single low-burden TP53 mutation. Patients harbouring low-burden TP53 mutations had significantly lower time to first treatment compared to patients with wild-type TP53. Our study has expanded the knowledge on the frequency, clonal architecture, and clinical impact of low-burden TP53 mutations. By demonstrating that patients with sole low-burden TP53 variants represent more than one-third of patients with TP53 mutations and have an increased risk for treatment initiation, our findings strengthen the need to redefine the threshold of TP53 variant reporting to below 10% in the routine diagnostic setting., (© 2023 The Authors. The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland and John Wiley & Sons Ltd.)

Peripheral T-cell lymphomas (PTCLs) expressing multiple follicular T helper (TFH) cell-related antigens are now classified as TFH lymphomas (TFHL), including angioimmunoblastic, follicular, and not otherwise specified (NOS) types. CXCR5 is the TFH cell-defining chemokine receptor that, together with its ligand CXCL13, plays a critical role in the development of follicles and the positioning of TFH and B cells within follicles. A comprehensive immunomorphologic study was performed to investigate the expression pattern of CXCR5 in a large cohort of nodal PTCLs, particularly those with a TFH cell phenotype, and to compare its expression with six other TFH cell-related antigens. We found that CXCR5 is widely expressed in neoplastic TFH cells, except in TFHL-NOS, and represents a specific marker of this lymphoma entity. Our results suggest that CXCR5 directs the distribution of neoplastic T cells in the affected lymph nodes and may influence the formation of the pathognomic pathological FDC network.

Background: Hypereosinophilic syndrome (HES) is a peripheral eosinophilia characterized by elevated absolute eosinophil cell count ( > 1.500 cells/ μ L) and consequent tissue and end-organ damage. Our aim was to evaluate the mitral annular (MA) and/or tricuspid annular (TA) parameters of patients with HES and to determine whether there are any changes in these parameters compared to healthy individuals., Methods: 17 patients with HES were involved in our study, 2 cases were excluded due to suboptimal image quality (mean age of the evaluated patients: 61.7 ± 11.2 years, 10 males). Their data were compared with those of 24 healthy subjects (mean age: 55.2 ± 7.9 years, 12 males) in the control group. Complete echocardiographic examinations were performed including two-dimensional (2D) Doppler echocardiography and three-dimensional echocardiography (3DE) to assess the MA and the TA., Results: Comparing the echocardiographic parameters of the HES patients with those of the healthy volunteers, the following changes were seen: the interventricular septum was significantly thickened in HES patients, no other significant changes were detected between the examined patient groups. End-diastolic and end-systolic MA diameters, areas and perimeters were increased and MA fractional area change and MA fractional shortening were decreased in HES patients. From TA morphological parameters, only end-diastolic TA area and end-systolic TA perimeter were significantly increased in HES patients. Functional TA parameters showed no significant alterations in the HES group. In patients with HES, no correlations could be detected between 2D and 3D echocardiographic data with the examined laboratory findings., Conclusions: The extent of the dilation of the MA is more pronounced than that of the TA in HES. MA functional impairment is present in HES., Competing Interests: The authors declare no conflict of interest. Attila Nemes is serving as one of the Editorial Board members of this journal. We declare that Attila Nemes had no involvement in the peer review of this article and has no access to information regarding its peer review. Full responsibility for the editorial process for this article was delegated to Zhonghua Sun and Yung-Liang Wan., (Copyright: © 2023 The Author(s). Published by IMR Press.)

Background: Ibrutinib is widely known as an effective and well-tolerated therapeutical choice of the chronic lymphocytic leukaemia (CLL). However, acquired resistance may occur during the treatment, causing relapse. Early detection of ibrutinib resistance is an important issue, therefore we aimed to find phenotypic markers on CLL cells the expression of which may correlate with the appearance of ibrutinib resistance. Methods: We examined 28 patients' peripheral blood (PB) samples (treatment naïve, ibrutinib sensitive, clinically ibrutinib resistant). The surface markers' expression (CD27, CD69, CD86, CD184, CD185) were measured by flow cytometry. Furthermore, the BTK C481S resistance mutation was assessed by digital droplet PCR. Moreover, the CLL cells' phenotype of a patient with acquired ibrutinib resistance was observed during the ibrutinib treatment. Results: The expression of CD27 ( p = 0.030) and CD86 ( p = 0.031) became higher in the clinically resistant cohort than in the ibrutinib sensitive cohort. Besides, we found that high CD86 and CD27 expressions were accompanied by BTK C481S mutation. Our prospective study showed that the increase of the expression of CD27, CD69 and CD86 was noticed ahead of the clinical resistance with 3 months. Conclusion: Our study suggests that the changes of the expression of these markers could indicate ibrutinib resistance and the examination of these phenotypic changes may become a part of the patients' follow-up in the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Takács, Kotmayer, Czeti, Szalóki, László, Mikala, Márk, Masszi, Farkas, Plander, Weisinger, Demeter, Fekete, Szerafin, Deák, Szaleczky, Sulák, Borbényi and Barna.)

Introduction: Hemophilia is an inherited disorder due to deficiencies in factor VIII (type A) and factor IX (type B). Abnormalities in myocardial mechanics could be theorized due to hemophilia-associated hypocoagubility and related quantitative and qualitative changes of the blood. The present study aimed a detailed assessment of left atrial (LA) volumetric and functional properties in patients with hemophilia using three-dimensional speckle-tracking echocardiography (3DSTE)., Materials and Methods: The study consisted of 12 subjects with hemophilia type A and 2 cases with hemophilia type B (mean age: 40.8 ± 19.1 years, all males). Results of hemophilia patients were compared to that of 23 age-, gender- and risk factor-matched controls (42.4 ± 9.0 years, all males). Routine two-dimensional Doppler echocardiography and 3DSTE were performed in all subjects., Results: LA volumes respecting cardiac cycle did not differ between controls and hemophilia patients. From LA volume-based functional properties, LA stroke volumes were similar between the groups examined in all phases of LA function. While total atrial emptying fraction featuring LA reservoir function was reduced in patients with hemophilia compared to that of controls, passive and active atrial emptying fraction characterizing LA conduit and booster pump functions were similar between the groups. From LA strains, peak mean segmental circumferential and longitudinal LA strains were impaired in patients with hemophilia, other peak LA strains were similar between the groups. LA strains at atrial contraction did not differ between groups of hemophilia patients and controls., Conclusions: Hemophilia is not associated with LA volumetric changes, but mild LA functional abnormalities are present., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Cardiovascular Echography.)

Introduction: Amyloidosis is a rare condition due to extracellular deposition of excessive amount of protein in parenchymal tissues including the heart. The present study aimed to test whether cardiac amyloidosis (CA) is associated with morphological and functional abnormalities of the tricuspid annulus (TA). For this aim, the results of patients having CA were compared to age- and gender-matched healthy controls by three-dimensional speckle-tracking echocardiography (3DSTE). Moreover, differences in TA parameters between light-chain CA (AL-CA) and transthyretin CA (TTR-CA) were studies as well., Materials and Methods: The study comprised 27 CA patients (mean age: 62.7 ± 9.1 years, 21 males), their results were compared to those of 20 age- and gender-matched healthy volunteers (59.3 ± 3.8 years, 13 males). Complete two-dimensional Doppler echocardiography and 3DSTE were performed in all CA patients and controls., Results: Dilated end-diastolic and end-systolic TA diameter, area and perimeter could be detected in all CA patients and in the AL-CA and TTR-CA subgroups, as well. Although only a few TTR-CA patients were involved, morphologic TA parameters proved to be tendentiously higher as compared to those of AL-CA patients. Functional parameters of TA were found to be reduced in CA patients, which were more deteriorated in AL-CA patients., Conclusions: Dilated TA is associated with its functional deterioration in CA., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Background: Hemophilia is an X-linked inherited disorder primarily affecting males, its major types are type A (deficiency in factor VIII) and B (deficiency in factor IX), and is considered to be the most common severe congenital coagulation factor deficiency. The present study was designed to test whether any differences in left ventricular (LV) rotational mechanics could be demonstrated between male patients with hemophilia and healthy controls using three-dimensional speckle-tracking echocardiography (3DSTE)-derived virtual LV models., Methods: The present study consisted of 17 patients with hemophilia, however, 3 patients were excluded due to insufficient image quality. In the remaining patient population, 12 patients had hemophilia A and 2 patients had hemophilia B (mean age: 42.2±18.9 years, all males). The control group comprised 16 age-matched healthy subjects (46.0±5.9 years, all males)., Results: None of the routine two-dimensional echocardiographic data differ between patients with hemophilia and controls. None of the patients and controls showed ≥ grade 1 valvular regurgitations and had valvular stenoses. In one subject, the near absence of LV twist called as LV "rigid body rotation" could be detected, data of which were managed separately. While 3DSTE-derived apical LV rotation was 3.65 degrees, basal LV rotation proved to be 3.57 degrees leading to 0.08-degree LV apico-basal gradient suggesting counterclockwise LV "rigid body rotation". In the remaining patients, both LV apical rotation (7.25±6.20 vs. 10.39±4.16 degrees, P<0.02) and LV twist (10.24±5.60 vs. 14.38±3.93 degrees, P<0.003) showed significant impairment in patients with hemophilia., Conclusions: LV rotational abnormalities are present in hemophilia with reduced LV apical rotation and twist., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/qims-21-30). AN serves as an unpaid editorial board member of Quantitative Imaging in Medicine and Surgery. The other authors have no conflicts of interest to declare., (2022 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Background: Patients with hematological malignancies (HM) are at high risk of mortality from SARS-CoV-2 disease 2019 (COVID-19). A better understanding of risk factors for adverse outcomes may improve clinical management in these patients. We therefore studied baseline characteristics of HM patients developing COVID-19 and analyzed predictors of mortality., Methods: The survey was supported by the Scientific Working Group Infection in Hematology of the European Hematology Association (EHA). Eligible for the analysis were adult patients with HM and laboratory-confirmed COVID-19 observed between March and December 2020., Results: The study sample includes 3801 cases, represented by lymphoproliferative (mainly non-Hodgkin lymphoma n = 1084, myeloma n = 684 and chronic lymphoid leukemia n = 474) and myeloproliferative malignancies (mainly acute myeloid leukemia n = 497 and myelodysplastic syndromes n = 279). Severe/critical COVID-19 was observed in 63.8% of patients (n = 2425). Overall, 2778 (73.1%) of the patients were hospitalized, 689 (18.1%) of whom were admitted to intensive care units (ICUs). Overall, 1185 patients (31.2%) died. The primary cause of death was COVID-19 in 688 patients (58.1%), HM in 173 patients (14.6%), and a combination of both COVID-19 and progressing HM in 155 patients (13.1%). Highest mortality was observed in acute myeloid leukemia (199/497, 40%) and myelodysplastic syndromes (118/279, 42.3%). The mortality rate significantly decreased between the first COVID-19 wave (March-May 2020) and the second wave (October-December 2020) (581/1427, 40.7% vs. 439/1773, 24.8%, p value < 0.0001). In the multivariable analysis, age, active malignancy, chronic cardiac disease, liver disease, renal impairment, smoking history, and ICU stay correlated with mortality. Acute myeloid leukemia was a higher mortality risk than lymphoproliferative diseases., Conclusions: This survey confirms that COVID-19 patients with HM are at high risk of lethal complications. However, improved COVID-19 prevention has reduced mortality despite an increase in the number of reported cases., (© 2021. The Author(s).)

In Hungary, the cost of lenalidomide-based therapy is covered only for relapsed multiple myeloma (MM) patients, therefore lenalidomide is typically used in the second-line either as part of a triplet with proteasome inhibitors or as a doublet. Lenalidomide-dexamethasone is a standard treatment approach for relapsed/refractory MM, and according to recent large randomized clinical trials (RCT, the standard arm of POLLUX, ASPIRE, TOURMALINE), the progression-free survival (PFS) is expected to be approximately 18 months. We surveyed ten Hungarian centers treating MM and collected data of 278 patients treated predominantly after 2016. The median age was 65 years, and patients were distributed roughly equally over the 3 international staging system groups, but patients with high risk cytogenetics were underrepresented. 15.8% of the patients reached complete response, 21.6% very good partial response, 40.6% partial response, 10.8% stable disease, and 2.5% progressed on treatment. The median PFS was unexpectedly long, 24 months, however only 9 months in those with high risk cytogenetics. We found interesting differences between centers regarding corticosteroid type (prednisolone, methylprednisolone or dexamethasone) and dosing, and also regarding the choice of anticoagulation, but the outcome of the various centers were not different. Although the higher equivalent steroid dose resulted in more complete responses, the median PFS of those having lower corticosteroid dose and methylprednisolone were not inferior compared to the ones with higher dose dexamethasone. On multivariate analysis high risk cytogenetics and the number of prior lines remained significant independent prognostic factors regarding PFS ( p < 0.001 and p = 0.005). Our results show that in well-selected patients Lenalidomide-dexamethasone can be a very effective treatment with real-world results that may even outperform those reported in the recent RCTs. This real world information may be more valuable than outdated RCT data when treatment options are discussed with patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Varga, Dávid Tóth, Réka Szita, Csukly, Hardi, Gaál-Weisinger, Nagy, Altai, Rencsik, Plander, Szendrei, Kórád, Radványi, Rottek, Deák, Szaleczky, Schneider, Kohl, Kosztolányi, Alizadeh, Lengyel, Modok, Borbényi, Lovas, Váróczy, Illés, Rajnics, Masszi and Mikala.)

Introduction: Hypereosinophilic syndrome (HES) and immunoglobulin light-chain amyloidosis (ALA) are two, rare haematological disorders associated with cardiac alterations. Aim: The goal of the present study was a comparative assessment of left ventricular (LV) deformational parameters in HES and ALA patients using three-dimensional speckle-tracking echocardiography (3DSTE). Method: In the present study, results of 10 HES patients (mean age: 60.9 ± 14.7 years) and 19 ALA patients (mean age: 63.4 ± 7.8 years, 13 males) were analysed. The control group contained 13 age- and gender-matched healthy adults (mean age: 59.2 ± 4.3 years, 5 males). All patients underwent a complete two-dimensional Doppler echocardiography followed by 3DSTE. Results: All basal segmental LV strains were significantly reduced in ALA patients as compared to the control group. Global and mean segmental LV longitudinal strain (LS) values of ALA patients proved to be significantly decreased as compared to those of the healthy control group. During comparison of HES patients and healthy controls, significant difference could be detected in global LV-LS, while segmental basal LV-LS was also significantly reduced in HES patients. Basal LV radial and 3D strains showed significant differences when parameters of HES and ALA patient groups were compared. Conclusion: 3DSTE is a feasible tool for the detailed assessment of LV deformation in HES and ALA patients. Significant LV deformational abnormalities could be detected in both groups. In the case of ALA, these abnormalities are more prominent. Orv Hetil. 2020; 161(5): 169-176.

Introduction: Hypereosinophilic syndrome (HES) is a very heterogeneous group of disorders with varied etiologies characterized by peripheral eosinophilia and eosinophilic tissue/end-organ damage. Three-dimensional speckle-tracking echocardiography (3DSTE) was used for assessment of left ventricular (LV) rotational mechanics in HES patients., Methods: The study comprised 13 HES patients, from which one patient was excluded due to insufficient image quality. The remaining patient population consisted of 12 HES cases (mean age: 59.7 ± 13.7 years, eight males). The control group consisted of 36 healthy volunteers (mean age: 52.9 ± 8.3 years, 23 males). 3DSTE was used for the evaluation of LV rotational abnormalities., Results: Both LV apical rotation (4.86 ± 1.92 degree vs 10.07 ± 3.92 degree, P < .0001) and LV twist (8.52 ± 2.79 degree vs 14.41 ± 4.26 degree, P < .0001) showed significant deteriorations in most of HES patients. Time-to-peak LV apical rotation (380 ± 115 ms vs 344 ± 69 ms, P = .56), LV basal rotation (335 ± 148 ms vs 337 ± 111 ms, P = .89), and LV twist (348 ± 91 ms vs 320 ± 60 ms, P = .64) were not significantly different between HES patients and controls. No correlations could be detected between absolute eosinophil count and eosinophil ratio and apical LV rotation (r = 0.12, P = .51 and r = 0.23, P = .45, respectively) and LV twist (r = 0.24, P = .39 and r = 0.31, P = .34, respectively). In two subjects, the absence of LV twist called LV "rigid body rotation" (RBR) was detected., Conclusions: Reduced LV apical rotation and twist could be demonstrated in HES. LV-RBR could be detected in some HES patients., (© 2019 Wiley Periodicals, Inc.)

Daratumumab is a human anti-CD38 monoclonal antibody used in the treatment of refractory and relapsed multiple myeloma. We investigated the efficacy and safety of daratumumab therapy in a real-world setting. Ninety-nine Hungarian patients were included; 48 received monotherapy, while lenalidomide and bortezomib combinations were administered in 29 and 19 cases, respectively. Overall response rate was assessable in 88 patients, with 12 complete, 10 very good partial, 34 partial, and seven minor responses. At a median duration of follow-up of 18.6 months, median progression-free survival (PFS) among all patients was 17.0 months. These values were inferior in the bortezomib combination and monotherapy groups. Patients with early-stage disease (ISS1) had better survival results than those with stage 2 or 3 myeloma (p = 0.009). Heavily pretreated patients had inferior PFS compared to those with 1-3 therapies (p = 0.035). Patients with impaired renal function had PFS results comparable with those having no kidney involvement. There were 10 fatal infections, and the most frequent adverse events were mild infusion-associated reactions and hematologic toxicities. Our results confirm that daratumumab is an effective treatment option for relapsed/refractory MM with an acceptable safety profile in patients with normal and impaired renal function.

Background: The present prospective, multinational, noninterventional study aimed to document and describe real-world treatment regimens and disease progression in multiple myeloma (MM) patients., Patients and Methods: Adult patients initiating any new MM therapy from October 2010 to October 2012 were eligible. A multistage patient/site recruitment model was applied to minimize the selection bias; enrollment was stratified by country, region, and practice type. The patient medical and disease features, treatment history, and remission status were recorded at baseline, and prospective data on treatment, efficacy, and safety were collected electronically every 3 months., Results: A total of 2358 patients were enrolled. Of these patients, 775 and 1583 did and did not undergo stem cell transplantation (SCT) at any time during treatment, respectively. Of the patients in the SCT and non-SCT groups, 49%, 21%, 14%, and 15% and 57%, 20%, 12% and 10% were enrolled at treatment line 1, 2, 3, and ≥ 4, respectively. In the SCT and non-SCT groups, 45% and 54% of the patients had received bortezomib-based therapy without thalidomide/lenalidomide, 12% and 18% had received thalidomide/lenalidomide-based therapy without bortezomib, and 30% and 4% had received bortezomib plus thalidomide/lenalidomide-based therapy as frontline treatment, respectively. The corresponding proportions of SCT and non-SCT patients in lines 2, 3, and ≥ 4 were 45% and 37%, 30% and 37%, and 12% and 3%, 33% and 27%, 35% and 32%, and 8% and 2%, and 27% and 27%, 27% and 23%, and 6% and 4%, respectively. In the SCT and non-SCT patients, the overall response rate was 86% to 97% and 64% to 85% in line 1, 74% to 78% and 59% to 68% in line 2, 55% to 83% and 48% to 60% in line 3, and 49% to 65% and 36% and 45% in line 4, respectively, for regimens that included bortezomib and/or thalidomide/lenalidomide., Conclusion: The results of our prospective study have revealed great diversity in the treatment regimens used to manage MM in real-life practice. This diversity was linked to factors such as novel agent accessibility and evolving treatment recommendations. Our results provide insight into associated clinical benefits., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Light-chain (AL) cardiac amyloidosis (CA) is characterized by fibril deposits, which are composed of monoclonal immunoglobulin light chains. The right ventricle is mostly involved in AL-CA and impairment of its function is a predictor of worse prognosis., Objectives: To characterize the volumetric and functional properties of the right atrium (RA) in AL-CA by three-dimensional speckle-tracking echocardiography (3DSTE)., Methods: A total of 16 patients (mean age: 64.5 ± 10.1 years, 11 males) with AL-CA were examined. Their results were compared to that of 15 age- and gender-matched healthy controls (mean age: 58.9 ± 6.9 years, 8 males). All cases have undergone complete two-dimensional Doppler and 3DSTE. A two-tailed p value of less than 0.05 was considered statistically significant., Results: Significant differences could be demonstrated in RA volumes respecting cardiac cycle. Total (19.2 ± 9.3% vs. 27.9 ± 10.7%, p = 0.02) and active atrial emptying fractions (12.1 ± 8.1 vs. 18.6 ± 9.8%, p = 0.05) were significantly decreased in AL-CA patients. Peak global (16.7 ± 10.3% vs. 31.2 ± 19.4%, p = 0.01) and mean segmental (24.3 ± 11.1% vs. 38.6 ± 17.6%, p =0.01) RA area strains, together with some circumferential, longitudinal and segmental area strain parameters, proved to be reduced in patients with AL-CA. Global longitudinal (4.0 ± 5.2% vs. 8.2 ± 5.5%, p = 0.02) and area (7.8 ± 8.1% vs. 15.9 ± 10.3%, p = 0.03) strains at atrial contraction and some circumferential and area strain parameters at atrial contraction were reduced in AL-CA patients., Conclusion: Significantly increased RA volumes and deteriorated RA functions could be demonstrated in AL-CA.

Follicular lymphoma is a lymphoid malignancy commonly showing slow progression which makes the treatment of the disease challenging. Rituximab monotherapy and rituximab added to standard chemotherapy has been proven to increase survival among patients with advanced stage of the disease. However, the benefit of a rituximab maintenance therapy after induction was still unclear at the time of the initiation of this study. HUSOM was a phase III open-label, single-arm, multi-centre study aimed to assess the efficacy and the safety of the 12 cycles of rituximab (375 mg/m 2 every 8 weeks) maintenance therapy in patients had already presented partial or complete response to R-CVP or R-CHOP. Efficacy endpoints such as event-free survival and overall survival were estimated. Adverse events were recorded during the entire course of the study. A total number of 124 patients were enrolled by 15 Hungarian study sites. Out of these, 86 patients received 12 cycles of rituximab and 69 patients completed the 3-year follow-up phase as well. The probabilities of the event free survival and progression at 4.3 years were estimated to be 70.3% and 74.4%, respectively. The overall and the disease free survival at 4 years were estimated to be 90.7% and 87.9%, respectively. A total number of 85 adverse events were reported during the study out of which 5 AEs were considered to be related to the administration of rituximab. Analyses of the efficacy variables have revealed comparable results to those reported by controlled clinical trials (EORTC 20981, PRIMA) conducted in parallel with the HUSOM study.

Objective: Cardiac amyloidosis (CA) is as an infiltrative disorder primarily caused by extracellular tissue deposition of amyloid fibrils in the myocardial interstitium. The current study was designed to test whether alterations in ascending aortic elastic properties could be detected by echocardiography in CA patients, and to compare their results to controls., Patients and Methods: We included 19 CA patients from which CA proved to be AL amyloidosis in 17 cases and transthyretin (TTR) amyloidosis in 2 cases. Their results were compared to 20 age-, gender-, and risk factor-matched controls., Results: There was significantly greater interventricular septum and left ventricular (LV) posterior wall thickness, lower LV ejection fraction and greater E/A in CA patients than in controls, suggesting systolic, and diastolic dysfunction. CA patients also showed significantly reduced aortic strain and pulsatile change in aortic diameter, and increased aortic stiffness index., Conclusion: These results suggest increased aortic stiffness in CA patients., (© 2017 Wiley Periodicals, Inc.)

Background: Philadelphia negative myeloproliferative neoplasms (MPNs) are characterized by frequent mutations of driver genes including JAK2, CALR and MPL. While the influence of JAK2 V617F mutant allele burden on the clinical phenotype of MPN patients is well-described, the impact of CALR mutant allele burden on clinical features needs further investigation., Patients and Methods: Quantitative assessment of JAK2 and CALR mutations was performed on diagnostic DNA samples from 425 essential thrombocythemia (ET) and 227 primary myelofibrosis patients using real-time quantitative PCR and fragment length analysis. Characterization of CALR mutations and detection of MPL mutations were performed by Sanger sequencing., Results: Twelve novel CALR mutations have been identified. ET patients with CALR mut load exceeding the median value exhibited lower hemoglobin values (12.0 vs. 13.6 g/dL), higher LDH levels (510 vs. 351 IU/L) and higher rate of myelofibrotic transformation (19% vs. 5%). The CALR mut load was higher among ET patients presenting with splenomegaly compared to those without splenomegaly (50.0% vs. 43.5%)., Conclusion: Our study confirms the clinical significance of driver mutational status and JAK2 mut load in MPNs; in addition, unravels a novel clinical association between high CALR mut load and a more proliferative phenotype in ET., (Copyright © 2017 Elsevier Ltd. All rights reserved.)