Hemato, Volume 4, Issue 3 (September 2023) – 7 articles

Kikuchi–Fujimoto disease (KFD) is a rare, benign lymphoproliferative disease of uncertain origin that can mimic other inflammatory or clonal lymphoproliferative disorders. Given the lack of available blood biomarkers, diagnosis is based on the biopsy of an affected lymph node. In recent years, evidence has been mounting that a dysregulated type I INF innate immune response plays a pivotal role in the pathogenesis of the disease and might be a future therapeutic target. Nonetheless, laboratory assays measuring the expression of interferon alpha (INFα) and INF-stimulated genes (ISGs) are cumbersome and not widely available, limiting their use in clinical and translational research and encouraging the use of more convenient surrogate markers. In this study, a rapid flow cytometry assay detected increased levels of expression of CD169 (Siglec-1), an INFα-induced surface protein involved in innate immunity regulation, on circulating monocytes from two patients with KFD. Our results are in line with previous experiences and set the stage for a more extended investigation into the use of this assay in exploring the pathophysiology of KFD. Full article

High frequencies of MYD88^L265P mutation are observed in IgM monoclonal gammopathies, and specifically in Waldenström macroglobulinemia (WM), indicating this mutation as a potential disease biomarker. Given the fact that MYD88^L265P mutation has been described as a key driver mutation, has increased our understanding of the biology behind MYD88 signaling and helped us to identify the functional components which could be targeted. On the other hand, the absence of the MYD88^L265P mutation in patients with IgM monoclonal gammopathies has been associated with a higher risk of transformation to aggressive lymphomas, resistance to several therapies, and shorter overall survival. The present review focuses on the molecular mechanisms that shape the signaling pattern in MYD88^WT cells, as well as on the clinical implications and therapeutic challenges of WM patients that harbor the MYD88^WT genotype. Full article

Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of chronic myeloid leukemia (CML), granting patients a life expectancy close to that of the normal population and, in a subset of patients, the possibility to discontinue therapy. Nonetheless, for a not negligible minority of patients, TKIs are not able to control CML. Allogeneic hematopoietic cell transplantation (HCT) has long been a pivotal therapy for CML. At present, allogeneic HCT is considered an option in CML patients diagnosed or progressing to blast phase (BP), for those in chronic phase (CP) resistant to multiple lines of TKI therapy or for those experiencing severe toxicity, mostly hematologic, under TKIs. Moving from real-world cases, we reviewed the results of allogeneic HCT in the setting of advanced-phase CML or failure of TKIs, with a focus on the progresses in transplant technology that has extended transplant options in elderly CML patients and in those lacking a sibling donor, and on the post-HCT strategies for prevention and treatment of disease relapse. Full article

Cryoglobulinaemia is characterised by serum immunoglobulins that precipitate at temperatures below 37 °C and redissolve on warming. Monoclonal IgM immunoglobulin can be associated with type I and II cryoglobulinaemia with underlying Waldenström macroglobulinemia, monoclonal gammopathy of undetermined significance, or another non-Hodgkin lymphoma. In this research, we review the clinical characteristics of monoclonal IgM-associated cryoglobulinaemia and suggest a management approach for addressing them. Laboratory testing is critical as even a minimal amount of measurable cryoglobulin may result in symptoms. Accurate detection of cryoglobulins may be challenging, care must be taken with preanalytical variables, and repeated testing of monoclonal protein and cryoglobulins is indicated if clinical suspicion is high. Presentations range from asymptomatic to showing multisystem involvement, meaning that careful evaluation of the features and a thorough interrogation of organ systems and the underlying clone are critical. Immediate management is required for clinical red-flag features. Due to their rarity, data to inform treatment decisions are scant and collaborative research is imperative must be conducted to aid researchers in efforts to define optimal treatment strategies. Full article

Anticoagulation clinics (ACs) have a greater impact on anticoagulation control than usual medical care (UMC). There is little evidence of the performance of AC in patients on warfarin living in low and middle-income countries. We sought to investigate the efficacy and safety of an AC in patients treated at a Brazilian public hospital. This was a randomized clinical trial that tested the efficacy of a recently implemented AC, compared to UMC, in outpatients with heart disease. The primary and secondary endpoints were time in the therapeutic range (TTR) and warfarin-related complications, respectively. Overall, 280 patients were enrolled and randomly assigned to Group A: one year at an AC (A1: first half-year; A2: second half-year); and Group B: first half-year receiving UMC (B1) and second half-year being assisted at the AC (B2). The mean age was 56.8 ± 13.1 years, and most patients were female (54.6%). Above 68% of patients had limited reading capability. A1 demonstrated greater TTR (62.4 ± 20.8%) than B1 (55.1 ± 28.5%) (p = 0.014). Group B improved TTR from 55.1 ± 28.5% (B1) to 62.2 ± 23.1% (B2) (p = 0.008). Despite the underpowered analysis of safety, A1 exhibited a lower incidence rate (IR) per patient-year (p-y) of total bleeding than B1 (incidence rate ratio (IRR): 0.78; p = 0.041) and a reduction in intra-group comparisons (both groups: IRR 0.58; p < 0.001). AC care helped increase TTR in a low-income setting showing favorable performance in a distinct population of those evaluated by previous studies. Extending AC care to similar populations may improve the outcomes of warfarin use. Full article

Since their introduction, tyrosine kinase inhibitors (TKIs) have radically changed the treatment paradigm of Chronic Myeloid Leukemia (CML), leading to deep and lasting molecular responses and profoundly influencing survival. However, cancer-therapy-related Cardiovascular Toxicities (CTR-CVTs) associated with BCR::ABL1 TKIs are one of the main sources of concern: hypertension, arterial occlusive events, arrhythmias, dysmetabolic alteration, and glomerular filtration impairment are frequently reported in clinical trials and real-life experiences. Therefore, a close interaction between hematologists and cardiologists becomes crucial to implementing prevention protocols based on a comprehensive assessment of baseline cardiovascular risk, the management of any detectable and modifiable risk factors, and the elaboration of a monitoring plan for CTR-CVTs during treatment. Here, we provide the most comprehensive and recent evidence in the literature on the pathophysiological patterns underlying CTR-CVTs, providing useful evidence-based guidance on the prevention and management of CVD risk factors at baseline and during treatment with BCR::ABL1 TKIs. Full article

The concept of gray-zone lymphoma (GZL) has been progressively refined since its introduction in the literature in 1998. For several years, it was applied to a rather broad spectrum of conditions, posing the problem of the differential diagnosis between any type of Hodgkin lymphoma (HL) and diffuse large B-cell lymphoma, with special reference to primary mediastinal forms (PMBL). Officially recognised as a provisional entity in the 4th and revised 4th editions of the WHO Classification of Tumour of Haematopoietic and Lymphoid Tissues with the term “B-cell lymphoma unclassifiable with features intermediate between diffuse large B-cell lymphoma and classic Hodgkin lymphoma”, it was limited to tumours showing either morphologic features reminiscent of classic HL (CHL) but carrying a complete B-cell phenotype or conversely provided with a PMBL morphology yet revealing CHL phenotypic characteristics. The definition of GZL has been further revised in the recently published International Lymphoma Classification and 5th edition of the WHO Classification of Haematolymphoid Tumours, which have limited it to mediastinal neoplasms (MGZL) based on emerging molecular evidence. The aim of this review is to critically discuss the issue of MGZL, as well as in light of the suboptimal response to current therapies. Full article