Blood Reviews

Poor graft function (PGF) after allogeneic hematopoietic stem cell transplantation (HCT) is a serious complication with high morbidity and mortality. The reported incidence of PGF, its risk factors and outcome vary substantially between studies. This variability may be explained by heterogeneity in patient cohorts and HCT strategies, differences in the underlying causes of cytopenia, as well as by differences in PGF definition. In this systematic review and meta-analysis, we provide an overview of the various PGF definitions used and determined the impact of this variability on the reported incidence and outcome...

ME/CFS is a debilitating chronic condition that often develops after viral or bacterial infection. Insight from the study of Long COVID/Post Acute Sequelae of COVID-19 (PASC), the post-viral syndrome associated with SARS-CoV-2 infection, might prove to be useful for understanding pathophysiological mechanisms of ME/CFS. Disease presentation is similar between the two conditions, and a subset of Long COVID patients meet the diagnostic criteria for ME/CFS. Since Long COVID is characterized by significant vascular pathology - including endothelial dysfunction, coagulopathy, and vascular dysregulation - the question of whether or not the same biological abnormalities are of significance in ME/CFS arises...

Because of successful thalassaemia prevention programmes in resource-rich countries and it's huge population China now has the greatest number of new cases of thalassaemia globally as well as more people with thalassaemia than any other country. 30 million Chinese have thalassaemia-associated mutations and about 300,000 have thalassaemia major or intermedia requiring medical intervention. Over the past 2 decades there has been tremendous economic growth in China including per capita spending on health care...

Natural Killer (NK) cells yield promise in therapy of hematologic malignancies. The clinical experience with adoptively transferred allogeneic NK cells over past two decades has revealed safety and minimal risk of CRS or ICANS. Unlike T cells which have to be genetically altered to avoid graft vs host disease (GVHD), HLA mismatched NK cells can be infused without GVHD risk. This makes them ideal for the development of off-the-shelf products. In this review we focus on NK biology relevant to the cancer therapy, the trajectory of NK therapeutics for leukemia, lymphoma, and myeloma; and advantages of the NK cell platform...

Biological events that contribute to the pathogenesis of myelodysplastic syndromes/neoplasms (MDS) are becoming increasingly characterized and are being translated into rationally designed therapeutic strategies. Herein, we provide updates from the first International Workshop on MDS (iwMDS) of the International Consortium for MDS (icMDS) detailing recent advances in understanding the genetic landscape of MDS, including germline predisposition, epigenetic and immune dysregulation, the complexities of clonal hematopoiesis progression to MDS, as well as novel animal models of the disease...

Acute lymphoblastic/lymphocytic leukemia (ALL) occurring post-cancer diagnosis (secondary ALL - sALL) is increasingly recognized as a discrete entity, constituting up to as much as 5-10% of all new ALL diagnoses, and carrying its own biologic, prognostic and therapeutic significance. In this review, we will outline the history and current state of research into sALL. We will explore the evidence for differences underlining its existence as a distinct subgroup, as well as examining what might be driving such differences etiologically, including prior chemotherapy...

Peripheral T-cell lymphomas (PTCLs) are a diverse and uncommon type of lymphoid malignancies with a dismal prognosis. Recent advances in genomic studies have shown recurring mutations that are changing our knowledge of the disease's molecular genetics and pathogenesis. As such, new targeted therapies and treatments to improve disease outcomes are currently being explored. In this review, we discussed the current understanding of the nodal PTCL biology with potential therapeutic implications and gave our insights on the promising novel therapies that are currently under study such as immunotherapy, chimeric antigen receptor T-cell therapy, and oncolytic virotherapy...

Large Granular Lymphocyte (LGL) Leukemia is a rare, heterogeneous even more that once thought, chronic lymphoproliferative disorder characterized by the clonal expansion of T- or NK-LGLs that requires appropriate immunophenotypic and molecular characterization. As in many other hematological conditions, genomic features are taking research efforts one step further and are also becoming instrumental in refining discrete subsets of LGL disorders. In particular, STAT3 and STAT5B mutations may be harbored in leukemic cells and their presence has been linked to diagnosis of LGL disorders...

Adult T-cell leukemia/lymphoma (ATLL) has aggressive clinical behaviors, and improving its prognosis is a great challenge. A disease progression model from asymptomatic human T-cell leukemia virus type 1 carrier to aggressive-type ATLL has been proposed, and indolent ATLL comprising a smoldering or favorable chronic type is located at the midpoint. Even the most favorable smoldering type has a 4-year overall survival rate of <60%. Although watchful waiting is pervasive in patients with indolent ATLL, early therapeutic intervention is discussed among hematologists...

MDS and AML are clonal hematopoietic stem cell disorders of increasing incidence, having a variable prognosis based, among others, on co-occurring molecular abnormalities. TP53 mutations are frequently detected in these myeloid neoplasms and portend a poor prognosis with known therapeutic resistance. This article provides a timely review of the complexity of TP53 alterations, providing updates in diagnosis and prognosis based on new 2022 International Consensus Classification (ICC) and World Health Organization (WHO) guidelines...

Approval of new agents to treat higher risk (HR) myelodysplastic syndrome (MDS) has stalled since the approval of DNA methyltransferase inhibitors (DNMTi). In addition, the options for patients with lower risk (LR) MDS who have high transfusion needs and do not harbor ring sideroblasts or 5q- syndrome are limited. Here, we review the current treatment landscape in MDS and identify areas of unmet need, such as treatment after failure of erythropoiesis-stimulating agents or DNMTis, TP53-mutated disease, and MDS with potentially targetable mutations...

Despite the use of high-resolution molecular techniques for tissue typing, chronic graft-versus-host disease (cGVHD) remains a major complication following allogeneic hematopoietic stem cell transplant. cGVHD adversely affects the life-expectancy and quality of life. The latter is particularly important and functionally relevant in pediatric patients who have a longer life-expectancy than adults. Current laboratory evidence suggests that there is not any difference in the pathophysiology of cGVHD between adults and pediatric patients...

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BACKGROUND: Complementary and alternative medicine (CAM) is a popular alternative to opioid and other analgesics in sickle cell disease (SCD). We review the effectiveness, prevalence, and factors associated with CAM use in the pediatric SCD population. METHODS: The review protocol was created based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A literature search was conducted in MEDLINE, Embase, Cochrane Library, PubMed, and Web of Science...

About one-half of adults with acute B-cell lymphoblastic leukemia (B-ALL) who do not achieve molecular complete remission or who subsequently relapse are not cured by current chemo- or targeted therapies. Previously, the sole therapeutic option for such persons was a hematopoietic stem cell transplant. Recently, several immune therapies including monoclonal antibodies, bispecific T-cell engagers (BiTEs), antibody-drug conjugates (ADCs), and chimeric antigen receptor T-cells (CARs) have been shown safe and effective in this setting...

Amyloidosis is the term to define a broad array of rare protein misfolding syndromes. Among them, light chain (AL) amyloidosis is the most common, affecting roughly 10 people per million/year. The core purpose of the present literature review is to shed light on the academic and clinical knowledge on the condition, encompassing its i) epidemiology, ii) economic burden, and iii) quality of life consequences. The areas of interest are Europe and North America. Literature search was primarily performed on Embase® and finally integrated with additional, deemed eligible, sources...

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, life-threatening, acquired disease in which blood cells lacking complement regulatory proteins are destroyed because of uncontrolled complement activity. Since 2007, terminal complement inhibitors have revolutionized the treatment of this disease. However, patients treated with these inhibitors can still experience anemia because of C3-mediated extravascular hemolysis and clinically relevant levels of breakthrough or residual intravascular hemolysis. Proximal complement inhibitors, which are only just beginning to emerge, have the potential to address this problem by targeting components of the pathway upstream of C5, thereby protecting patients against both intra- and extravascular hemolysis...

The cause(s) of most cases of leukaemia is unknown. Save for several rare inherited disorders the most convincingly-identified causes of leukaemia are exposures to ionizing radiations, to some chemicals and to some anti-cancer drugs. Data implicating ionizing radiations as a cause of leukaemias come from several sources including persons exposed to the atomic bomb explosions in Japan, persons receiving radiation therapy for cancer and other disorders, persons occupationally exposed to radiation such as radiologists and nuclear facility workers, cigarette smokers, and others...

Over the past few years, we have gained a deeper understanding of clonal hematopoiesis of indeterminate potential (CHIP), especially with regard to the epidemiology, clinical sequelae, and mechanical aspects. However, interventional strategies to prevent or delay the potential negative consequences of CHIP remain underdeveloped. In this review, we highlight the latest updates on clonal hematopoiesis research, including molecular mechanisms and clinical implications, with a particular focus on the evolving strategies for the interventions that are being evaluated in ongoing observational and interventional trials...

Multiple myeloma is a hematological neoplasm characterized by abnormal proliferation of plasma cells in the bone marrow and is usually associated with increased bone pain and skeletal-related events such as pathological fracture and/or spinal cord compression. Myeloma bone disease results in changes in the bone-marrow microenvironment evidenced by increased osteoclastic activity and/or decreased osteoblastic activity, which negatively affect quality of life. Treatment of myeloma bone disease includes bisphosphonates or denosumab (bone-modifying agents)...