Hemato, Volume 3, Issue 3 (September 2022) – 13 articles

Extramedullary hematopoiesis is rarely seen in patients with myelodysplastic syndromes, and its clinical characterizations are not well-defined. Here, we systematically reviewed the published literature to summarize the clinical manifestations, treatments, and long-term outcomes of biopsy-proven extramedullary hematopoiesis in patients with myelodysplastic syndromes. We included 41 patients, and ring sideroblasts were the most common myelodysplastic subtype (30.6%). Extramedullary hematopoiesis was typically symptomatic on presentation due to local compression, frequently involving the liver or spleen (36.6%), or the paravertebral region (24.4%). Notably, ring sideroblasts were predominantly seen in patients with non-hepatosplenic involvement (38.5 vs. 6.7%, p = 0.034). Interventions, when required, usually included surgery (36.8%) or radiation (13.2%), which led to symptomatic improvement in 55.5% of patients. The median overall survival of the current cohort was 7 months. The current study confirms the rarity of extramedullary hematopoiesis as a complication of myelodysplastic syndromes; however, its outcomes in response to systemic modern therapies require further investigation. Full article

Acute myeloid leukemia (AML) is a highly heterogeneous hematologic malignancy characterized by the clonal proliferation of hematopoietic stem and progenitor cells (HSPCs) and blockade of differentiation and proliferation of immature myeloid cells that accumulate in bone marrow at the expense of normal hematopoiesis. AMLs originate from the expansion of HSPCs progressively acquiring somatic mutations. The development of high-throughput sequencing techniques has helped to discover the genetic heterogeneity and complexity of AMLs, revise diagnostic and prognostic criteria, and to identify new therapeutic targets. These studies have allowed the identification of several recurrent driver mutations and the definition of a rational molecular classification of these tumors. In parallel, the development of techniques for the determination of single-cell mutational profiling has considerably contributed to understanding the clonal heterogeneity and evolution of AMLs. The acquisition of these genetic data coupled with the identification of molecular therapeutic targets has determined a considerable expansion of the therapeutic armamentarium, with the development of several new drugs highly active against specific AML subtypes. These developments have increased the interest and the need for sensitive techniques for the identification of minimal residual disease, the population of leukemia cells that survives despite morphological remission and causes disease relapse. Full article

Lymphomas in people living with HIV (PLWH) are associated with Epstein Barr virus (EBV) and Kaposi-sarcoma-associated herpesvirus (KSHV). They include primary effusion lymphoma, large B-cell lymphoma arising in multicentric Castleman disease, plasmablastic lymphoma, Burkitt lymphoma, diffuse large B-cell lymphoma, and Hodgkin lymphoma (HL). Inclusion of these lymphomas in the WHO classification of tumors of hematopoietic and lymphoid tissues and the increasing recognition of these disorders have resulted in established clinical management that has led to improved outcomes. In this review, we report on the current management in lymphomas occurring in PLWH with an emphasis on KSHV-associated disorders and EBV-related HL. We also report on the simultaneous occurrence of KSHV- and EBV-associated disorders and highlight preventive measures that have been planned for tumor prevention in PLWH. In conclusion, it is recommended that treatment choice for PLWH affected by lymphoma, and receiving effective combined antiretroviral therapy (cART), should not be influenced by HIV status. Moreover, there is an urgent need (1) to reduce the current large disparities in health care between HIV-infected and HIV-uninfected populations, (2) to disseminate effective treatment, and (3) to implement preventive strategies for PLWH. Full article

Multiple myeloma (MM) is a hematological malignancy characterized by a high risk for thrombotic episodes, mainly venous thromboembolism (VTE). This risk is accentuated by cancer treatments such as immunomodulatory drugs (IMiDs). Cancer-associated thrombosis is one of the leading causes of mortality and morbidity, and the prevention of thrombosis is, therefore, of paramount significance. To this day, it is unclear which type of thromboprophylaxis is the most effective. This is partly due to the multifactorial etiology behind thrombosis since the compound of patient-, disease- and treatment-associated factors characterizing each patient with MM is unique. Additionally, the established risk scores are not reliable in patients with MM. The scope of this review is to summarize the factors contributing to increased thrombosis risk in MM, as well as the risk scores and thromboprophylaxis regimes available. Full article

Mantle cell lymphoma (MCL) is an aggressive yet incurable B-cell lymphoma that was only first recognized as a distinct subtype in 1992, with early reports suggesting a poor median survival. Elaine Jaffe is a renowned hematopathologist and scientist from the National Cancer Institute who was instrumental in many of the early descriptions of MCL that distinguished it from other B-cell lymphomas. Further, she has led multiple international collaborations that have harmonized the lymphoma classification systems that are currently in use today. The early morphologic descriptions of MCL along with the contributions of immunologic and genetic techniques have confirmed MCL as a distinct entity with unique biology and clinical behavior. Importantly, these scientific discoveries laid the foundation for unprecedented therapeutic breakthroughs that have led to significant improvements in overall survival. Full article

Technological and informatics advances as well as the availability of well-annotated and reliable genomic data have ushered in the era of genomics research. We describe in this brief review how the genomics approach has impacted lymphoma research in the understanding of the pathogenesis and biology of lymphoma, in lymphoma diagnosis and in targeted therapy. Some exciting directions that could be explored in the future are also discussed. Full article

Caring for a child with an acute/life threatening disease exposes parents to multiple stressors and challenges, resulting in a physical and psychological burden. Parents experience many health-related issues and worries that often remain underestimated. The aims of the study were: (a) to explore the associations between needs/disease-related issues and burden in parents of children with leukemia or Hodgkin’s disease; (b) to estimate predictors of parents’ burden using a stepwise linear regression analysis. Children (N = 33) followed an active therapy protocol (48.5%), or they were off therapy (51.5%). Forty-four parents completed surveys on caregiver burden levels and needs to cope with the child’s illness. Parental factors impacting burden (personal resources, loss of control, depression) and child’s quality of life (QoL) were also assessed. Among the needs, information about the illness/resources were the most urgently expressed by parents, followed by reassurance against fears for the child’s development and future well-being. Parents reported severe (27.3%) and moderate (22.7%) burden, with a higher percentage of caregivers with severe burden in the off-therapy phase (18.2%) than in the active-therapy phase (9.1%). The child’s decreased physical QoL and parent’s loss of control predicted higher levels of burden. The implications for supportive interventions aimed at responding to parental needs and preventing caregiver burden are discussed. Full article

The definitions of follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) are evolving in the era of personalized medicine. Early stages of the evolution of FL have been recognized. Two histological manifestations of early lesions are in situ follicular neoplasia and duodenal type FL. Additionally, FL frequently undergoes histological transformation, the most common form being DLBCL. High-grade B-cell lymphoma with double hit, with translocations involving BCL2 and MYC are important clinically. Rarer forms of transformation include classic Hodgkin lymphoma (CHL) and histiocytic sarcoma. In addition to conventional FL associated with the BCL2 translocation, alternative forms of BCL2-negative FL have been observed. These are heterogenous clinically and genetically. A distinctive group of B-cell lymphomas of follicle cell derivation arise in young patients and include pediatric type FL, testicular FL and a large B-cell lymphoma with IRF4 rearrangement. Historically DLBCL was separated into only two histological variants, centroblastic and immunoblastic. In 2017 the WHO classification recommended (1) the segregation of activated B cell and germinal center B cell derived DLBCL, (2) the identification of high-grade B-cell lymphoma with double hit, and (3) the recognition of an aggressive lymphoma that may resemble Burkitt lymphoma, currently designated in the International Consensus Classification as Large B-cell lymphoma with 11q aberration. Today we appreciate greater genomic complexity among aggressive B-cell lymphomas. Recent studies with NGS and mutational profiling have identified clinically significant genetic subgroups. It is hoped that these data ultimately will lead to targeted therapy based on the genetic profile. Full article

The prognosis and clinical outcomes for patients with multiple myeloma have improved significantly over the past two decades. A substantial number of patients now achieve complete remission after induction therapy, and more sensitive methods are needed to assess response. Minimal or measurable residual disease (MRD) has been incorporated in many clinical trials as well as in clinical practice. The importance of MRD assessment and correlation between MRD negativity and prolonged progression-free and overall survival has been confirmed in numerous clinical trials and several meta-analyses. Recent studies have even suggested that MRD negativity can partly overcome the impact of the negative prognostic factors such as high-risk cytogenetics or adverse revised international scoring system (R-ISS) stage. MRD can be measured in the bone marrow via imaging and via emerging blood-based techniques. The most common methods are multicolor flow cytometry and next-generation sequencing of bone marrow samples. Using these methods in optimal settings, MRD negativity with a sensitivity level of 10⁻⁶ can be detected. In this review, we discuss the benefits and limitations of these techniques as well as the clinical implications. Full article

Burkitt lymphoma (BL) is a rare non-Hodgkin lymphoma first described in 1958 by Denis Burkitt in African children. BL occurs as three types, endemic, which occurs in Africa and is causally attributed to Epstein-Barr virus and P. falciparum infections; sporadic, which occurs in temperate areas, but the cause is obscure; and immunodeficiency-type, which is associated with immunosuppression. All BL cases carry IG∷MYC chromosomal translocations, which are necessary but insufficient to cause BL. We report a comprehensive study of the geographic, sex, and age-specific patterns of BL among 15,122 cases from Cancer Incidence in Five Continents Volume XI for 2008–2012 and the African Cancer Registry Network for 2018. Age-standardized BL rates were high (>4 cases per million people) in Uganda in Africa, and Switzerland and Estonia in Europe. Rates were intermediate (2–3.9) in the remaining countries in Europe, North America, and Oceania, and low (<2) in Asia. Rates in India were 1/20th those in Uganda. BL rates varied within and between regions, without showing a threshold to define BL as endemic or sporadic. BL rates were twice as high among males as females and showed a bimodal age pattern with pediatric and elderly peaks in all regions. Multi-regional transdisciplinary research is needed to elucidate the epidemiological patterns of BL. Full article

The Peroxisome proliferator-activated receptors (PPARs) play vital roles in regulating cellular differentiation, proliferation, and caspase-mediated cell death pathways. They are regarded as promising targets for anti-tumor drug development, particularly for multiple myeloma (MM) and different hematological malignancies. Several early section clinical trials are conducted to measure the clinical practicableness of PPAR agonists, notably PPARα and PPARγ agonists, against various cancers. A spread of studies has investigated PPARs expression in metabolic regulation. Furthermore, it has been suggested that careful designing of partial agonists for PPARs may show improvement with side effects and increase the therapeutic value. This review summarizes the organic chemistry and metabolic actions of PPARs, and the therapeutic potential of their agonists underneath clinical development. It investigates therapeutic agents for hematologic malignancies. Full article

Amyloidosis is a rare, systemic disease that can result in significant functional impairment. Specific guidelines for the rehabilitation assessment of amyloidosis patients have yet to be established. The purpose of this study was to identify functional deficits and assess differences based on disease type, organ involvement, age, and gender of patients with amyloidosis. Materials and Methods: The multidisciplinary Comprehensive Amyloidosis Clinic (CAC) at Ohio State University (OSU) has developed structured assessment guidelines for amyloidosis patients. A retrospective, single-institution review of patients assessed in CAC between December 2017 and April 2020 was performed. Outcome measure data from the Timed Up and Go (TUG), 30 s sit-to-stand, and physical function portion of the SF 36 were gathered by chart review. Comparisons were made between CAC patient scores and normative data. Kruskal–Wallis tests were used to compare scores across the disease types (light chain, transthyretin wild-type, and hereditary variant transthyretin) and the Mann–Whitney U test was used for pairwise comparisons within disease types and cardiac involvement. Linear regression models were used to assess associations between patient characteristics (including age, gender, disease type, and cardiac involvement) and performance scores. Results: Data from sixty-four patients was evaluated. On the 30-s sit-to-stand test, patients with light chain amyloidosis performed 3.32 fewer repetitions than patients with transthyretin wild-type, p = 0.03. Patients with cardiac involvement had 2.55 fewer repetitions than patients without cardiac involvement, p = 0.03. Older patients were found to have slower TUG performance, and a 10-year increase in age was associated with an 11% increase in TUG scores. Conclusions: Findings indicate patients with light chain amyloidosis and patients with cardiac involvement, when compared to other amyloidosis patients, present with more physical impairments. Full article

The introduction of new and more effective therapeutic options for Multiple Myeloma (MM) has significantly deepened and prolonged patients’ remission. As currently used treatment protocols induce high rates of complete responses, Measurable Residual Disease (MRD) assessment has become essential to enhance the evaluation of treatment efficacy. Detection of MRD has improved with the development of highly sensitive and standardized techniques such as Next Generation Flow or Next Generation Sequencing, complemented by functional imaging techniques. These advances offer a valuable opportunity to further optimize criteria of response to treatment. Currently, extensive data demonstrate that MRD status is a valuable prognostic factor of survival. Since MRD represents a real measurement of disease burden, its incorporation in clinical trials to guide treatment decisions will certainly translate into clinical benefits. Sustained MRD negativity can be used to consider optimal candidates for treatment discontinuation, whereas MRD positive high-risk patients may have access to novel immunotherapeutic strategies such as bispecific drugs or CAR T cell therapy. In this review, we describe the available techniques to detect MRD, address the current data regarding MRD as a surrogate endpoint within clinical trials, examine how MRD can be introduced into the clinical management of MM patients, and discuss the future of MRD monitoring. Full article