bluuebunny/crossref_metadata_2025_split huggingface dataset:
The intersection of sickle cell disease, stigma, and pain in Africa
Authors: Anie Kofi A. 
Published: December 2024

Abstract
Sickle cell disease (SCD) is a significant public health concern in sub-Saharan Africa, where it is the most prevalent genetic disorder, presenting numerous health care and sociocultural challenges. A case study of a young girl from Ghana's Ashanti region illustrates the stigma surrounding SCD, driven by traditional beliefs and misconceptions that perceive SCD as a spiritual affliction. This stigma results in social ostracism and discrimination, impacting affected individuals and their families. Despite the severe and unpredictable pain associated with SCD, effective management is often hampered by limited health care resources and infrastructure. In Ghana and other African countries, inadequate pain relief and a lack of specialized care worsen the suffering of people with SCD. Health care providers' responses vary from empathy to dismissal, reflecting broader systemic issues in care delivery. Stigma has extensive effects, including social exclusion, psychological distress, and educational setbacks. The case study underscores the vital role of community education and support networks, such as those provided by the Sickle Cell Foundation of Ghana and Sickle Cell Association of Ghana, in reducing humiliation and enhancing the lives of those affected by SCD. Addressing the complex challenges of SCD in Africa requires comprehensive strategies. Improving the health care infrastructure, promoting community education, and establishing robust support systems are crucial to alleviating the burden of SCD, with the involvement of both government and nongovernmental organizations. These measures help create a more inclusive and understanding environment for individuals living with this chronic condition, enhancing their quality of life and overall well-being.
Transfusions, disease-modifying treatments, and curative therapies for sickle cell anemia in Africa: where are we now?
Authors: Odame Isaac , Bazuaye Godwin Nosakhare 
Published: December 2024

Abstract
The mortality burden of sickle cell anemia (SCA) is centered in sub-Saharan Africa. In addition to a lack of systematic programs for early diagnosis, access to disease-modifying treatments is limited to only a few urban centers. Providing a safe and adequate blood supply is a major challenge, heightening mortality from SCA-associated complications that require urgent blood transfusion and making the delivery of regular transfusion therapy for stroke prevention nonfeasible. Hydroxyurea therapy with proven clinical benefits for pain episodes, acute chest syndrome, malaria, transfusions, hospitalizations, and stroke prevention is the most feasible treatment for SCA in Africa. Access barriers to hydroxyurea treatment include poor availability, unaffordable costs, health professionals' reluctance to prescribe, a lack of national guidelines, and exaggerated fears about drug toxicities. Strategies for the local manufacture of hydroxyurea combined with the systematic education and training of health professionals using guidelines supported by the World Health Organization can help surmount the access barriers. Hematopoietic stem cell transplantation as a curative therapy is available in only 7 countries in Africa. The few patients who have suitable sibling donors and can afford a transplant must usually travel out of the country for treatment, returning to their home countries where expertise and resources for posttransplant follow-up are lacking. The recently developed ex-vivo gene therapies are heavily dependent on technical infrastructure to deliver, a daunting challenge for Africa. Future in-vivo gene therapies that bypass myeloablation and ex-vivo processing would be more suitable. However, enthusiasm for pursuing these gene therapies should not overlook strategies to make hydroxyurea universally accessible in Africa.
BPDCN: state of the art
Authors: Pemmaraju Naveen 
Published: December 2024

Abstract
The emergence of blastic plasmacytoid dendritic cell neoplasm (BPDCN) as its own distinct entity within the pantheon of hematologic malignancies is due to the growing understanding of its unique multiorgan clinical presentation and characteristic skin lesions. The occurrence of BPDCN is generally heralded by a multicompartmental presentation of violaceous cutaneous lesions, involvement by bone marrow and/or blood, lymph node invasion, and an inclination toward extramedullary organ involvement, including, most remarkably, central nervous system (CNS)/cerebrospinal fluid positivity. With a median age historically of ≥ 70 years and up to 5:1 male predominance in most of the field's earlier studies, the most notable development in the modern era is the recognition of emerging important groups with BPDCN, such as female, pediatric, and adolescent/young adult patients; CNS + BPDCN patients; and an increasing number of cases being diagnosed worldwide. These trends are in line with the increased educational and research efforts, greater international collaboration, and markedly improved diagnostic tools and clinical approaches among hematology/oncology, hematopathology, dermatology, and dermatopathology teams around the world. Now, with over 5 years since the first commercially approved targeted agent specifically dedicated for BPDCN, the CD123-targeted agent tagraxofusp, improvements have been demonstrated particularly in the frontline setting for patients with BPDCN. The field is abundant with hope, as it has experienced advancements including greater molecular characterization, expanded identification of potential targets for therapy beyond CD123, advent of combination therapies, improving parameters for stem cell transplantation, and novel clinical trials specifically available for patients with BPDCN.
How to think about acute leukemia of ambiguous lineage
Authors: Weinberg Olga K. 
Published: December 2024

Abstract
Classification of acute leukemia involves assigning lineage by resemblance of blasts to normal progenitor cells. This approach provides descriptive information that is useful for disease monitoring, provides clues to pathogenesis, and can help to select effective chemotherapeutic regimens. Acute leukemias of ambiguous lineage (ALAL) are those leukemias that either fail to show evidence of myeloid, B-lymphoid, or T-lymphoid lineage commitment or show evidence of commitment to more than 1 lineage, including mixed-phenotype acute leukemia (MPAL). The different treatment regimens for acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) make ALAL a challenge both diagnostically and therapeutically. Current classification criteria have reduced the reported incidence of mixed lineage leukemias by emphasizing fewer markers and categorizing some biphenotypic leukemias with recurrent cytogenetic abnormalities as other entities. Several recent studies have explored the genomic and epigenetic landscape of MPAL and emphasize the genomic heterogeneity of MPAL. Two classification proposals of myeloid malignancies recently been published and include International Consensus Classification and fifth edition of the World Health Organization Classification of Haematolymphoid Tumours. Our review aims to discuss the diagnostic challenges in the setting of classification updates, recent genomic studies, and therapeutic strategies in this poorly understood disease.
von Willebrand disease and heavy menstrual bleeding: when and how to test
Authors: Perez Botero Juliana 
Published: December 2024

Abstract
von Willebrand disease (VWD) is a common inherited bleeding disorder caused by von Willebrand factor (VWF) deficiency and is an important cause of heavy menstrual bleeding in young patients. A clinical evaluation using standardized bleeding scores helps determine when screening hemostatic testing is indicated by identifying patients with a moderate or high probability of an inherited bleeding disorder. The diagnosis of VWD is made when VWF levels are under 30 IU/dL or between 30 and 50 IU/dL when there is a positive bleeding history. Activity levels above 100 IU/dL have a high negative predictive value. Multiple factors, including stress from acute bleeding and anemia, pregnancy, and medications, can affect VWF levels, hence testing for VWD is best performed when a person's health is at its baseline level, although this is not always possible in clinical practice. Variation in assay methodologies measuring VWF activity can have a significant impact on the diagnostic evaluation, and it is important for clinicians to be familiar with the limitations of the assay used by their local or reference laboratory. Genetic testing can be useful in establishing the VWD subtype and providing accurate reproductive counseling but is not required to make a diagnosis.
Demystifying autoimmune HIT: what it is, when to test, and how to treat
Authors: Scully Marie , Lester William A. 
Published: December 2024

Abstract
Antibodies to platelet factor 4 (PF4) have been primarily linked to classical heparin-induced thrombocytopenia (cHIT). However, during the rollout of the COVID-19 vaccine program a new condition, vaccine-induced thrombocytopenia and thrombosis (VITT), was identified, related to adenoviral-based COVID-19 vaccines. The differences between these 2 conditions, both clinically and in laboratory testing, set the scene for the development of a new rapid anti-PF4 assay that is not linked with heparin (as relevant for cHIT). Concurrently, there has been a reassessment of those cases described as autoimmune HIT. Such scenarios do not follow cHIT, but there is now a clearer differentiation of heparin-dependent and heparin-independent anti-PF4 conditions. The importance of this distinction is the identification of heparin-independent anti-PF4 antibodies in a new subgroup termed VITT-like disorder. Cases appear to be rare, precipitated by infection and in a proportion of cases, orthopaedic surgery, but are associated with high mortality and the need for a different treatment pathway, which includes immunomodulation therapy.
Relapsed/refractory CLL: the role of allo-SCT, CAR-T, and T-cell engagers
Authors: Kater Arnon P. , Siddiqi Tanya 
Published: December 2024

Abstract
Chronic lymphocytic leukemia (CLL) patients who are refractory to both Bruton's tyrosine kinase and B-cell/CLL lymphoma 2 (BCL2) inhibitors face a significant treatment challenge, with limited and short-lasting disease control options. This underscores the urgent need for novel therapeutic strategies. Immunotherapy has emerged as a promising approach to address this unmet need, offering the potential for durable remissions and improved patient outcomes. Historically, allogeneic stem cell transplantation has been used for high-risk CLL patients, demonstrating promising survival rates. However, its applicability is limited by high treatment-related mortality and chronic graft-versus-host disease, especially in older and frail patients. Chimeric antigen receptor (CAR) T-cell therapy is gaining attention for its potential in relapsed/refractory CLL. Early clinical trials have shown that CAR T cells can induce durable remissions, with encouraging overall response rates in heavily pretreated patients. Additionally, bispecific antibodies are being explored as immunotherapeutic strategies, showing promising preclinical and early clinical results in targeting CLL cells effectively. One of the major challenges in CLL treatment with T-cell–based therapies is the acquired T-cell dysfunction observed in patients. To overcome these limitations, strategies such as combining targeted agents with cellular immunotherapies, modifying CAR designs, and incorporating immunomodulatory compounds into the manufacturing process are being investigated. These innovative approaches aim to enhance T-cell engagement and improve outcomes for CLL patients, offering hope for more effective and sustainable treatments in the future.
MGCS: where do we stand today?
Authors: Iberri David , Liedtke Michaela 
Published: December 2024

Abstract
Monoclonal gammopathies of clinical significance (MGCS) are a heterogeneous group of disorders characterized by the presence of an indolent B-cell or plasma-cell clone producing a toxic monoclonal immunoglobulin resulting in end-organ dysfunction. MGCS is a clinicopathologic diagnosis that requires the demonstration of a monoclonal immunoglobulin in the correct clinical setting. The most common MGCS syndromes are renal, neurologic, and cutaneous, although hematologic and multi-organ MGCS syndromes are also increasingly recognized. Therapy most commonly targets the underlying clonal population; immunoglobulin-targeting therapies as well as complement and cytokine antagonists have emerged for selected MGCS syndromes and may be temporizing in a subset of patients. Other chapters review renal and neurologic MGCS; this chapter focuses on hematologic and multi-organ MGCS syndromes.
Renal manifestations of MGUS
Authors: Bridoux Frank , Nasr Samih H. , Arnulf Bertrand , Leung Nelson , Sirac Christophe , Jaccard Arnaud 
Published: December 2024

Abstract
Kidney disease is a common complication of monoclonal immunoglobulin (MIg)–secreting B-cell disorders and predominantly occurs in patients who do not meet the criteria for an overt hematological disease. To distinguish this situation from monoclonal gammopathy of undetermined significance, which lacks organ damage, the term monoclonal gammopathy of renal significance (MGRS) was introduced to depict the association of a small, otherwise indolent B-cell clone, with renal disease induced by the secreted MIg. The spectrum of renal disorders in MGRS is wide, encompassing both tubular and glomerular disorders, classified according to the composition of deposits and their ultrastructural pattern of organization. Renal lesions, independent of the tumor burden, are mostly governed by the molecular characteristics of the MIg variable domain and involve either direct (deposition or precipitation) or indirect (autoantibody activity, complement activation) mechanisms. The diagnosis, often suggested by careful analysis of renal and extrarenal symptoms, almost always requires histological confirmation by a kidney biopsy with light, immunofluorescence, and electron microscopy studies. Most patients do not have a known monoclonal gammopathy at presentation. Hematologic investigations should include serum and urine protein electrophoresis and immunofixation, serum-free light chain measurements, and bone marrow studies with flow cytometry and cytogenetics to determine the nature of the pathogenic clone (most commonly plasmocytic). Early diagnosis before the development of severe chronic kidney disease and rapid achievement of deep hematological response through clone-targeted chemotherapy (currently based on proteasome inhibitor and monoclonal anti-CD38 antibody–based combinations for plasma cell clones) are the main factors influencing long-term renal and patient outcomes.
When to use stem cell transplantation for classical Hodgkin lymphoma
Authors: Perales Miguel-Angel , Ahmed Sairah 
Published: December 2024

Abstract
Hodgkin lymphoma (HL) is a rare hematologic malignancy with a bimodal distribution of incidence, with most patients diagnosed between the ages of 15 and 30 years and another peak in patients older than 55 years. It is estimated that in 2023, almost 9000 people were diagnosed with HL in the United States. Most patients will be cured using conventional chemotherapy and radiotherapy. The treatment of HL has changed significantly over the past decade following the approval of highly effective novel therapies, including brentuximab vedotin and the checkpoint inhibitors (CPIs) nivolumab and pembrolizumab. The increasing use of these novel therapies has resulted in decreased utilization of both autologous and allogeneic hematopoietic cell transplantation (HCT) in patients with HL. In this review, we discuss the role of stem cell transplantation in patients with HL, with a particular focus on recent data supporting allogeneic HCT as a curative option in patients who progress on or are intolerant to CPI treatment.
Supportive care in myeloma—when treating the clone alone is not enough
Authors: Zweegman Sonja , van de Donk Niels W. C. J. 
Published: December 2024

Abstract
The overall survival in patients with multiple myeloma has increased over recent decades. This trend is anticipated to further advance with the emergence of T-cell–redirecting therapies, including chimeric antigen receptor T-cell (CAR T) therapy and T-cell–engaging bispecific antibodies. Despite these therapeutic improvements, treatment-related adverse events impede quality of life. This underscores the imperative of optimizing supportive care strategies to maximize treatment outcomes. Such optimization is crucial not only for patient well-being but also for treatment adherence, which may translate into long-term disease control. We here describe a) how to prevent bone disease, b) a risk-adapted thrombosis prophylaxis approach, c) the management of on-target, off-tumor toxicity of G-protein–coupled receptor class C group 5 member D-targeting T-cell–redirecting therapies, and d) infectious prophylaxis, with a focus on infections during T-cell–redirecting therapies
Transplant in myeloma: who, when, and why?
Authors: Perrot Aurore 
Published: December 2024

Abstract
High-dose melphalan supported by autologous transplantation has been the standard of care for eligible patients with newly diagnosed multiple myeloma for nearly 30 years. Several randomized clinical trials have reaffirmed the strong position of transplant in the era of triplets combining proteasome inhibitors, immunomodulatory drugs, and dexamethasone. Although quadruplets are becoming the standard in transplantation programs, no data are currently available on the need for a transplant with new regimens incorporating anti-CD38 monoclonal antibodies. Outcomes remain heterogeneous, with different response depths and durations depending on the cytogenetics at diagnosis. The improvement of disease prognostication using sensitive and specific tools allows for adapting the strategy to initial and dynamic risks. This review examines which patients need a transplant, when transplantation is preferable, and why.
IgG4-related disease for the hematologist
Authors: Chen Luke Y. C. 
Published: December 2024

Abstract
Immunoglobulin G4–related disease (IgG4-RD) is an immune-mediated disease with many important manifestations in hematopoietic and lymphoid tissue. IgG4 is the least naturally abundant IgG subclass, and the hallmark feature of IgG4-RD is markedly increased IgG4-positive plasma cells (with an IgG4 to IgG ratio &gt;40%) in affected tissue, along with elevated polyclonal serum IgG and IgG4 in most patients. Histological diagnosis is essential, and other key features include storiform fibrosis, lymphoplasmacytic infiltrate, tissue eosinophilia, and obliterative phlebitis. The disease can present with predominantly proliferative features, such as swollen lacrimal and salivary glands, orbital pseudotumor, autoimmune pancreatitis, polyclonal hypergammaglobulinemia (PHGG), eosinophilia, and tubulointerstitial nephritis of the kidneys, or predominantly fibrotic disease, including mediastinal and retroperitoneal fibrosis, sclerosing mesenteritis, and hypertrophic pachymeningitis. This review focuses on 4 key hematological manifestations: PHGG, IgG4-positive plasma cell enriched lymphadenopathy (LAD), eosinophilia, and retroperitoneal fibrosis (RPF). These features are found in 70%, 60%, 40%, and 25% of IgG4-RD patients, respectively, but can also represent key hematological “mimickers” of IgG4-RD, including Castleman disease (PHGG, LAD), eosinophilic vasculitis (eosinophilia, PHGG, LAD), hypereosinophilic syndromes (eosinophilia, LAD, PHGG), and histiocyte disorders (PHGG, LAD, RPF). An organized approach to these 4 manifestations, and how to distinguish IgG4-RD from its mimickers, is explained. Proliferative manifestations typically respond very well to treatment corticosteroids, rituximab, and other immunosuppressives, whereas chronic fibrotic disease may not be reversible with current treatment modalities.
Practical guide for disease-modifying medication management of children and adolescents with sickle cell disease
Authors: Walden Joseph , Creary Susan 
Published: December 2024

Abstract
Hydroxyurea has historically been the sole disease-modifying medication (DMM) for sickle cell disease (SCD). However, 3 newer DMMs, L-glutamine, voxelotor, and crizanlizumab, were approved for children and adolescents with SCD since 2017. Despite their emergence, treatment barriers, including access, affordability, and nonadherence, limit the optimization of DMMs in the clinical setting. Furthermore, there is limited work outlining real-world use and safety of the newer DMMs, and no published guidelines advise how best to select between DMMs or to use multiple in combination. Meanwhile, each DMM is associated with unique characteristics, such as tolerability, cost, and route of administration, which must be considered when weighing these options with patients and families. This article discusses DMMs for SCD and offers practical guidance on using the available DMMs in real-world settings based on published peer-reviewed studies and considering patient preferences. The recent withdrawal of one of these DMMs (voxelotor) from the market highlights the need for additional DMMs and evidence-based practices for adding DMMs and when to progress towards curative therapies.
ITP in pregnancy: diagnostics and therapeutics in 2024
Authors: Fogerty Annemarie E. 
Published: December 2024

Abstract
Thrombocytopenia will occur in 10% of pregnancies—ranging from the clinically benign to processes that can threaten both mother and fetus. Accurately identifying the specific etiology and appropriate clinical management is challenging due to the breadth of possible diagnoses and the potential of shared features among them. Further complicating diagnostic certainty is the lack of confirmatory testing for most possible pathophysiologies. Immune thrombocytopenia (ITP) is recognized in less than 0.1% of pregnancies but is the most common cause of thrombocytopenia in early trimesters. ITP is an autoimmune disease of IgG-mediated enhanced platelet clearance and reduced platelet production. While there is an increasing number of drugs approved to treat ITP and more being examined in clinical trials, few have been sufficiently studied in pregnancy, representing a major unmet need in clinical practice. As such, treatment options for ITP in pregnancy are limited to corticosteroids and immunoglobulin therapy, which will not be effective in all cases. Maternal ITP also may have fetal impact, and any proposed therapeutic intervention must account for this possibility. Optimal care requires multidisciplinary collaboration between hematology, obstetrics, and anesthesia to enhance diagnostic clarity, develop an optimized treatment regimen, and shepherd mother and neonate to delivery safely.
Hemostasis and thrombosis risks and management in vascular anomalies
Authors: Crary Shelley E. 
Published: December 2024

Abstract
The role of the hematologist in the management of vascular anomalies is evolving. Several vascular tumors and malformations are associated with complex coagulation derangements. Kaposiform hemangioendothelioma or tufted angiomas may present with a consumptive coagulopathy known as the Kasabach-Merritt phenomenon (KMP). The management of KMP is essential to reduce morbidity and mortality from this condition. Slow-flow vascular malformations (SFVM) are also frequently complicated by a coagulopathy requiring anticoagulation, especially during and after surgical procedures, and some of these conditions pose a high risk of venous thromboembolism. Pain in SFVM is also frequently responsive to anticoagulation as well. It is essential for a hematologist with expertise in vascular anomalies to assist in the management of these complex conditions as part of a multidisciplinary team to reduce morbidity and mortality. Through case-based discussions, we attempt to highlight the critical role of the hematologist in managing these anomalies.