Hemato, Volume 4, Issue 1 (March 2023) – 10 articles

Previous studies have shown the vulnerability of hematological patients with the Coronavirus disease of 2019 (COVID-19). We aimed to compare the outcomes and risk factors for poor survival in patients with hematological conditions hospitalized with COVID-19 infection. Single centre, retrospective, cohort study included all patients with a hematological condition admitted to Rajiv Gandhi Cancer Institute & Research Centre, New Delhi, India between 1 April 2020 and 31 May 2021. Of a total of 154 patients, 81 were in the pre-delta group and 73 were in the delta group out of which 21 (25.97%) in the pre-delta group and 24 (33.88%) patients in the delta group died. Haematological characteristics—age > 60 years, progressive hematological cancer, more than two lines of anti-cancer therapy, and active chemo-immunotherapy or targeted therapy were associated with higher mortality in the delta group. COVID-19 characteristics associated with higher mortality during the delta wave were severity of COVID infection, higher oxygen requirements, and COVID plasma therapy There were no deaths in individuals (n = 15) within the delta group who received COVID-19 vaccination. This study adds to the evidence that patients with hematological diseases are a particularly vulnerable group and the delta variant of the virus is associated with higher mortality. We could identify patient characteristics and features related to COVID-19 infection and underlying hematological conditions that were associated with poor outcomes in the delta sub-group. Vaccination was found to be an effective strategy for overcoming mortality and morbidity in these patients. Full article

Background: Non-communicable diseases are often associated with chronic inflammation, placing patients suffering from these conditions at a higher risk of thrombosis and other complications. The pathophysiology of asthma and/or atopic asthma is also linked to chronic inflammation, which consequently may alter blood parameters including erythrocyte structure and function. Methodology: The objective of this study was to evaluate differences in erythrocytes between patients with atopic asthma (n = 30) and healthy individuals (n = 30) by evaluating routine haematological parameters; structures and axial ratios of erythrocytes using light microscopy; erythrocyte membrane elasticity using atomic force microscopy; and erythrocyte ultrastructure using scanning electron microscopy. Results: The haematological findings of healthy participants and patients suffering from asthma were within normal clinical ranges together with significantly higher levels of circulating monocytes (p = 0.0066), erythrocytes (p = 0.0004), haemoglobin (p = 0.0057), and haematocrit (p = 0.0049) in asthma patients. The analysis of eosin-stained erythrocytes by light microscopy showed more echinocytes, acanthocytes, and ovalocytes compared to controls and a significant difference in axial ratios (p < 0.0001). Atomic force microscopy findings showed reduced erythrocyte membrane elasticity in asthmatic erythrocytes (p = 0.001). Ultrastructural differences in erythrocytes were visible in the asthma group compared to controls. Conclusion: Altered erythrocyte ultrastructural morphology and a significant change in the haematological profile are evident in atopic asthma and may influence common complications associated with asthma. The impact of these changes on the physiological mechanisms of coagulation and the pathophysiology of asthma needs to be further elucidated. Full article

Pneumonia is among the most serious manifestations of HCMV infection, with high morbidity and mortality. Probable pneumonia is defined as the detection of HCMV in bronchoalveolar lavage (BAL) by viral isolation or DNA quantification (qPCR) combined with symptoms and/or signs of respiratory infection. However, currently, there is no reproducible and well-defined viral load (VL) from BAL that can reliably differentiate patients with pneumonia from the much more common detection of viral DNA in seropositive patients without true HCMV pneumonia. Several studies have been published with the aim of establishing an optimal VL for differentiating pneumonia from viral lung shedding. The aim of this review is to collect and analyze the methodology and the conclusions obtained in studies whose objectives included the correlation between HCMV VL in BAL and/or the plasma and the occurrence of HCMV pneumonia. For this purpose, a total of 14 articles have been included. There are some conclusions on which they all agree. PCR techniques were more sensitive and had a higher NPV than culture techniques but were less specific and had a low PPV. The mean HCMV loads in both BAL and the plasma were significantly higher in patients with pneumonitis than in those without. The HCMV load in patients with pneumonitis was higher in BAL than in the plasma, making qPCR in BAL a better predictor of HCMV pneumonitis than in the plasma. Nevertheless, this review highlights the difficulty of establishing a universal VL value, both in BAL and in the blood, to differentiate patients with HCMV pneumonia from those without. To complete the information available in these studies, prospective multicentre studies would be required. Methodologically, a large number of patients with HCMV pneumonitis would have to be included, and a subclassification of the type of immunosuppression of each patient should be made in order to obtain an optimal VL threshold in different host groups. Full article

In the past twenty years, tyrosine kinase inhibitors (TKIs) have substantially changed the therapeutic landscape and the clinical outcome of several cancers, including Philadelphia-chromosome positive chronic myeloid leukemia and acute lymphoblastic leukemia, chronic eosinophilic syndromes, gastrointestinal stromal tumors, and others. Despite the obvious advantages offered in terms of efficacy and the overall safety profile, this new class of agents presents novel side effects, sometimes different from those induced by conventional chemotherapy. Among others, the potential cardiac toxicity, characterized by possible arrhythmias and the highest rates of cardiac ischemic disease and heart failure, were predominantly investigated. In this article, the authors review the most significant evidence in this regard, highlighting the overall benefit of TKI usage and the need for careful monitoring, especially in elderly patients. Full article

Purpose: Oral mucositis (OM) is a common, debilitating complication of conditioning regimens for hematopoietic stem cell transplantation (HSCT). Supersaturated calcium phosphate rinse (SCPR) and palifermin have shown efficacy in preventing severe OM. However, whether their efficacy differs is unknown. We aimed to compare the efficacy of SCPR and palifermin in HSCT patients receiving myeloablative conditioning. Methods: A comprehensive review of our institutional database was performed to identify patients who received myeloablative-conditioning therapy over 5 years. All HSCT patients who received radiotherapy-based myeloablative conditioning and received either palifermin or SCPR within the study period were included. Most patients received Fludarabine, Busulfan, and total body irradiation (FBT). Patients were divided into two groups based on the OM prophylactic agent received. The primary outcome is prevalence of severe OM (WHO Grade 3 and 4). The secondary outcomes are a prevalence of all-grade OM and WHO Grade 4 OM. These outcomes were compared between the two groups. Results: We identified 26 patients who received SCPR and 122 patients who received palifermin for OM prophylaxis. The prevalence of World Health Organization (WHO) Grade 3 or 4 OM was significantly lower in the palifermin group (57% vs. 100%, p = 0.01). In addition, the palifermin group had lower WHO Grade 4 OM (22% vs. 62%, p = 0.0006). The overall prevalence of OM was not significantly different between the two groups (86% for palifermin group vs. 100% for SCPR arm, p = 0.15). Subgroup analyses demonstrated improved outcomes with palifermin, regardless of age, sex, disease status, donor type, and primary diagnosis. Conclusion: When compared to SCPR, the use of palifermin is associated reduced severity of OM in HSCT patients receiving radiotherapy-based myeloablative conditioning. Full article

The prognosis of adult acute lymphoblastic leukemia (ALL) is variable but more often dismal. Indeed, its clinical management is challenging, current therapies inducing complete remission in 65–90% of cases, but only 30–40% of patients being cured. The major determinant of treatment failure is relapse; consequently, measurement of residual leukemic blast (minimal residual disease, MRD) has become a powerful independent prognostic indicator in adults. Numerous evidences have also supported the clinical relevance of MRD assessment for risk class assignment and treatment selection. MRD can be virtually evaluated in all ALL patients using different technologies, such as polymerase chain reaction amplification of fusion transcripts and clonal rearrangements of antigen receptor genes, flow cytometric study of leukemic immunophenotypes and, the most recent, high throughput sequencing (HTS). In this review, the authors focused on the latest developments on MRD monitoring with emphasis on the use of HTS, as well as on the clinical impact of MRD monitoring. Full article

New insights from genomic studies have had an impact on the definition and the diagnosis of several lymphoid tumors including follicular B-cell lymphomas, aggressive diffuse large B-cell lymphomas, and lymphoproliferations associated with acquired and posttransplant immunodeficiencies. Follicular lymphoma (FL) includes tumors whose behavior varies widely from indolent/early lesions to aggressive/transformed lymphomas. Although some large B-cell lymphomas can be subclassified as specific entities, the majority lack the characteristics necessary for subclassification and, thus, are termed diffuse large B-cell lymphoma, NOS. There have been, however, some changes in the classification of specific subtypes of large B-cell lymphoma as well as the addition of new entities, a few of which are highlighted in this article. The immunodeficiency-related lymphoproliferative disorders are currently divided into four major categories based on the clinical setting in which they arose: primary immune deficiency, post-transplant, HIV infection, and iatrogenic immunosuppression. In the two upcoming classifications systems for hematolymphoid neoplasms, International Consensus Classification (ICC) and WHO-HAEM-5, there is a divergence in the approach to categorize these lesions. Furthermore, whereas the WHO-HAEM-5 confirms the ability to classify a spectrum of EBV+ lesions as EBV+ DLBCL, NOS, the ICC has separated out lesions that are composed of a heterogenous cellular infiltrate into a new separate category, “EBV-positive polymorphic B cell lymphoproliferative disorder, NOS”. Both WHO-HAEM-5 and ICC recognize a number of KSHV/HHV8-associated lymphoid lesions and acknowledge that there is significant overlap among the different lesions. In the future, translation of these innovations in general practice requires further validation. Full article

Immunoglobulin light chain (AL) amyloidosis is the most common type of systemic amyloidosis in China and is associated with increased morbidity and a poor prognosis. However, the clinical characteristics of Chinese patients with AL amyloidosis have not been systematically investigated. This scoping review aimed to summarize the available literature regarding the clinical characteristics of patients with AL amyloidosis and identify potential knowledge gaps. We searched three electronic databases from inception to 7 February 2021. PICOS (Patient, Intervention, Comparison, Outcome and Study) design structure was used to formulate the data extraction. All statistical calculations and analyses were performed with R (version 3.6.0). Sixty-seven articles with 5022 patients were included. Results suggest Chinese patients were younger (57 years) at the time of diagnosis when compared with other patient populations and were predominantly male (61.2%). The time interval from the onset of symptoms to diagnosis was between 6 and 12 months. It was found that 41.1% of Chinese patients with AL amyloidosis were diagnosed with an advanced stage III disease when diagnosed, and 20.2% had a concurrent disease. The most involved organs were the kidneys (84.3%) and the heart (62.5%). In conclusion, our study shows some similarities and differences with other studies on the clinical characteristics of Chinese patients with AL amyloidosis, including the age at diagnosis, Mayo stage, and organ involvement. However, a nationwide epidemiological investigation is still needed to provide a comprehensive overview of this patient population in China. Full article

The effective and sensitive monitoring of Minimal Residual Disease or Measurable Residual Disease (MRD) is a very important aspect in the management of patients affected by hematologic malignancies. The recent availability of new technologies has opened to the improvement of MRD monitoring. It is particularly relevant in patients affected by Chronic Myeloid Leukemia (CML). MRD monitoring is key in the management of CML patients thanks to the efficacy of TKIs therapy. Moreover, the policies of TKIs discontinuation aimed at treatment free remission are strongly based on the good selection of patients eligible for stopping TKIs therapy. The recently described application of digital PCR in CML patients monitoring seems to improve the accuracy and precision in the identification of optimal responders. The present review reports an overview on the application of digital PCR in the monitoring of MRD in CML and its impact on TKIs discontinuation trials and, consequently, on TFR success. Full article