bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transplant options and outcomes for TP53 myeloid disease
Authors: Fernández Hugo F. , Mishra Asmita 
Published: December 2024

Abstract
TP53-mutated myeloid disease is a constellation of abnormalities seen in both de novo and therapy-related acute myeloid leukemia and myelodysplastic syndrome. Historically, this group of disorders has had a poor prognosis. Newer treatment combinations allow patients to be treated with less toxicity. If response to induction therapy is achieved, fit and willing patients should be considered for allogeneic hematopoietic cell transplantation (HCT). The addition of allogeneic HCT to the treatment approach has modestly improved outcomes compared to chemotherapy alone, more so for those patients with disease control. Tailoring the conditioning regimen and maintenance therapy may improve outcomes in TP53 myeloid patients. In addition to chemotherapy, disease-modulating and immunological treatments continue to be studied to further improve outcomes.
Challenges in hospice and end-of-life care in the transfusion-dependent patient
Authors: Rodenbach Rachel , Caprio Thomas , Loh Kah Poh 
Published: December 2024

Abstract
Despite promising advances leading to improved survival, many patients with hematologic malignancies end up dying from their underlying disease. Their end-of-life (EOL) care experience is often marked by worsening symptoms, late conversations about patient values, increased healthcare utilization, and infrequent involvement of palliative care and hospice services. There are several challenges to the delivery of high-quality EOL care that span across disease, patient, clinician, and system levels. These barriers include an unpredictable prognosis, the patient's prognostic misunderstandings and preference to focus on the immediate future, and the oncologist's hesitancy to initiate EOL conversations. Additionally, many patients with hematologic malignancies have increasing transfusion requirements at the end of life. The hospice model often does not support ongoing blood transfusions for patients, creating an additional and substantial hurdle to hospice utilization. Ultimately, patients who are transfusion-dependent and elect to enroll in hospice do so often within a limited time frame to benefit from hospice services. Strategies to overcome challenges in EOL care include encouraging repeated patient-clinician conversations that set expectations and incorporate the patient's goals and preferences and promoting multidisciplinary team collaboration in patient care. Ultimately, policy-level changes are required to improve EOL care for patients who are transfusion-dependent. Many research efforts to improve the care of patients with hematologic malignancies at the end of life are underway, including studies directed toward patients dependent on transfusions.
Practical guide to the diagnosis and management of heparin-induced thrombocytopenia
Authors: May Jori , Cuker Adam 
Published: December 2024

Abstract
Heparin-induced thrombocytopenia (HIT) is an immune reaction to heparin associated with thrombocytopenia, thrombotic risk, and a high risk of morbidity and mortality. Given the frequent use of heparin and the common occurrence of thrombocytopenia in hospitalized patients, the diagnosis and management of HIT is a recurrent challenge in everyday inpatient care. This article presents practical guidance and tools to support the individual clinician providing evidence-based care to patients with suspected or confirmed HIT. The optimal diagnostic evaluation requires the stepwise use of risk-stratification tools and laboratory assays. Management requires the selection and use of nonheparin anticoagulation in these complex patients with both increased thrombotic risk and possible concurrent increased bleeding risk due to thrombocytopenia. Each step in the diagnostic and management process has important nuances and complexities, many of which vary based on patient characteristics and institutional resources. Given the many challenges of HIT care, truly practical management is best achieved when tools are implemented to support the delivery of consistent, high quality, and cost-effective care across health systems.
Iron overload in acquired sideroblastic anemias and MDS: pathophysiology and role of chelation and luspatercept
Authors: Gattermann Norbert 
Published: December 2024

Abstract
Besides transfusion therapy, ineffective erythropoiesis contributes to systemic iron overload in myelodysplastic syndromes with ring sideroblasts (MDS-RS) via erythroferrone-induced suppression of hepcidin synthesis in the liver, leading to increased intestinal iron absorption. The underlying pathophysiology of MDS-RS, characterized by disturbed heme synthesis and mitochondrial iron accumulation, is less well understood. Several lines of evidence indicate that the mitochondrial transporter ABCB7 is critically involved. ABCB7 is misspliced and underexpressed in MDS-RS, due to somatic mutations in the splicing factor SF3B1. The pathogenetic significance of ABCB7 seems related to its role in stabilizing ferrochelatase, the enzyme incorporating iron into protoporphyrin IX to make heme. Although iron-related oxidative stress is toxic, many patients with MDS do not live long enough to develop clinical complications of iron overload. Furthermore, it is difficult to determine the extent to which iron overload contributes to morbidity and mortality in older patients with MDS, because iron-related complications overlap with age-related medical problems. Nevertheless, high-quality registry studies showed that transfusion dependency is associated with the presence of toxic iron species and inferior survival and confirmed a significant survival benefit of iron chelation therapy. The most widely used iron chelator in patients with MDS is deferasirox, owing to its effectiveness and convenient oral administration. Luspatercept, which can reduce SMAD2/SMAD3-dependent signaling implicated in suppression of erythropoiesis, may obviate the need for red blood cell transfusion in MDS-RS for more than a year, thereby diminishing further iron loading. However, luspatercept cannot be expected to substantially reduce the existing iron overload.
Has PD-1 blockade changed the standard of care for cHL?
Authors: Kuczmarski Thomas M. , Lynch Ryan C. 
Published: December 2024

Abstract
The treatment paradigm for classic Hodgkin lymphoma (CHL) continues to evolve, particularly in light of the incorporation of programmed cell death protein 1 (PD-1) inhibitors into a variety of therapeutic settings. PD-1 inhibitors have demonstrated high efficacy and a favorable toxicity profile when added to a doxorubicin, vinblastine, dacarbazine chemotherapy backbone in patients with untreated CHL. PD-1 inhibitors are also effective treatment options in the relapsed/refractory setting. For patients who are pursuing autologous stem cell transplant (ASCT), pembrolizumab plus gemcitabine, vinorelbine, and liposomal doxorubicin has shown marked efficacy and is an effective treatment regimen to administer prior to transplant. For patients who either are not eligible for ASCT or have relapsed after ASCT, pembrolizumab or nivolumab monotherapy have been well studied and demonstrate high efficacy even when patients have been exposed to numerous lines of prior therapy. As data from previous trials continue to mature and new clinical trials are conducted, PD-1 inhibitors will continue to become an integral component for successful management of CHL.
Molecular profiling in MPN: who should have it and why?
Authors: Chee Ashlyn , Mead Adam J. 
Published: December 2024

Abstract
Philadelphia chromosome–negative myeloproliferative neoplasms (MPNs) are a group of blood cancers that result from somatic mutations in hematopoietic stem cells, causing constitutive activation of JAK-STAT signaling pathways with consequent overproduction of 1 or more myeloid lineages. The initiating event in MPN pathogenesis is a genetic mutation, and consequently molecular profiling is central to the diagnosis, risk stratification, and, increasingly, monitoring of therapy response in persons with MPN. In this review we summarize current approaches to molecular profiling of classical MPNs (essential thrombocythemia, polycythemia vera, and myelofibrosis), using illustrative clinical case histories to demonstrate how genetic analysis is already fully integrated into MPN diagnostic classification and prognostic risk stratification. Molecular profiling can also be used in MPN to measure response to therapy both in clinical trials and increasingly in routine clinical practice. Taking a forward look, we discuss how molecular profiling in MPN might be used in the future to select specific molecularly targeted therapies and the role of additional genetic methodologies beyond mutation analysis.
Pregnancy: MPN management before, during, and after pregnancy
Authors: How Joan , Hobbs Gabriela 
Published: December 2024

Abstract
The aging obstetric population, combined with more frequent myeloproliferative neoplasm (MPN) diagnoses in younger patients, will result in hematologic providers increasingly caring for MPN patients in pregnancy. There are special considerations that pertain to management of pregnancy in MPN patients. This includes increased risks of thrombosis and hemorrhage as well as pregnancy complications that are likely related to placental dysfunction associated with an MPN diagnosis, including preeclampsia, preterm delivery, and intrauterine growth restriction. Complicating these outcomes is the uncertainty of the safety of many commonly used drugs in MPNs in pregnancy and breastfeeding. Given the overall low incidence of pregnancy in MPNs, many guidelines are based on expert opinions and extrapolation from other high-risk pregnancy populations. In this case-based review, we summarize the literature on MPN pregnancy outcomes and synthesize recommendations to provide guidance on the antepartum and postpartum management of MPN patients. Special attention is also made to issues relevant to preconception, including fertility and the use of assisted reproductive technology.
What is the ideal approach—doublet, triplet, or quadruplet(s)?
Authors: Kumar Shaji K. 
Published: December 2024

Abstract
Significant progress has been made in the treatment of multiple myeloma (MM), with the introduction of several new drugs with different mechanisms of action. The treatment of newly diagnosed MM has evolved dramatically with the development of highly effective combinations that include 1 or more of the new drugs. Despite the continuing improvement in the overall survival of patients with MM, nearly a quarter of the patients have significantly inferior survival, often driven by a combination of factors, including tumor genetics and host frailty. The focus of initial therapy remains rapid control of the disease with reversal of the symptoms and complications related to the disease with minimal toxicity and a reduction in early mortality. The selection of the specific regimen, to some extent, depends on the ability of the patient to tolerate the treatment and the underlying disease risk. It is typically guided by results of randomized clinical trials demonstrating improvements in progression-free and/or overall survival. While increasing risk calls for escalating the intensity of therapy by using quadruplet combinations that can provide the deepest possible response and the use of autologous stem cell transplant, increasing frailty calls for a reduction in the intensity and selective use of triplet or doublet regimens. The choice of subsequent consolidation treatments and maintenance approaches, including duration of treatment, also depends on these factors, particularly the underlying disease risk. The treatment approaches for newly diagnosed myeloma continue to evolve, with ongoing trials exploring bispecific antibodies as part of initial therapy and CAR T cells for consolidation.
EBV and post-transplant lymphoproliferative disorder: a complex relationship
Authors: El-Mallawany Nader Kim , Rouce Rayne H. 
Published: December 2024

Abstract
Post-transplant lymphoproliferative disorders (PTLD) are a heterogeneous category of disease entities occurring in the context of iatrogenic immune suppression. Epstein-Barr virus (EBV)–driven B-cell lymphoproliferation represents the prototype of quintessential PTLD, which includes a range of histologies named nondestructive, polymorphic, and monomorphic EBV+ diffuse large B-cell lymphoma (DLBCL) PTLD. While EBV is associated with the majority of PTLD cases, other drivers of lymphoid neoplasia and lymphoma transformation can occur—with or without EBV as a codriver—thus underlining its vast heterogeneity. In this review, we discuss the evolution in contemporary PTLD nomenclature and its emphasis on more precise subcategorization, with a focus on solid organ transplants in children, adolescents, and young adults. We highlight the fact that patients with quintessential EBV-associated PTLD—including those with monomorphic DLBCL—can be cured with low-intensity therapeutic approaches such as reduction in immune suppression, surgical resection, rituximab monotherapy, or rituximab plus low-dose chemotherapy. There is, though, a subset of patients (approximately 30%-40%) with quintessential PTLD that remains refractory to lower-intensity approaches, for whom intensive, lymphoma-specific chemotherapy regimens are required. Other forms of monomorphic PTLD, which are as diverse as the spectrum of defined lymphoma entities that also occur in immunocompetent patients, are rarely cured with lower-intensity therapies and appear to be better categorized as posttransplant lymphomas. These distinct scenarios represent the variations in lymphoid pathology that make up a conceptual framework for PTLD consisting of lymphoid hyperplasia, neoplasia, and malignancy. This framework serves as the basis to inform risk stratification and determination of evidence-based treatment strategies.
Beyond IV push: alternative methods for management of acute pain in SCD
Authors: Azul Melissa , Brandow Amanda M. 
Published: December 2024

Abstract
Acute pain in sickle cell disease (SCD) involves multiple, complex downstream effects of vaso-occlusion, ischemia, and inflammation, ultimately resulting in severe and sudden pain. Historically, opioids and nonsteroidal anti-inflammatory drugs (NSAIDs) have been the cornerstone of treatment for acute SCD pain. However, given the evolving understanding of the complexity of pain pathways in SCD and the desire to avoid NSAID and opioid-induced side effects, a multimodal approach is needed to effectively treat acute SCD pain. In this article we review recent research supporting the utilization of nonopioid pharmacologic interventions and nonpharmacologic interventions while also describing the research questions that remain surrounding their use and efficacy and effectiveness in the management of acute SCD pain. Furthermore, we review care delivery processes shown to improve acute SCD pain outcomes and highlight areas where more work is needed. Through this comprehensive approach, alternative mechanistic pathways may be addressed, leading to improved SCD pain outcomes.
Novel clinical care models for patients with sickle cell disease
Authors: Bartolucci Pablo 
Published: December 2024

Abstract
This educational program outlines the importance of evolving clinical care models in response to increased life expectancy and variability in individual patient experiences, particularly in the context of sickle cell disease (SCD). It emphasizes the need for personalized and adaptive care models, in which the patient should play a central role, and the need for collaborative networks of physicians and caregivers, taking into account the multisystemic nature of the disease. The proposal also discusses the role of personalized medicine and technological advances, highlighting the need for a shared medical record; the balance between rare center expertise and widespread dissemination of knowledge; and the challenges in high- and low-income countries. It emphasizes the need to move toward personalized medicine, given the significant interindividual variability in both follow-up and treatment, and the introduction of more appropriate biomarkers and predictive algorithms to aid decision-making. The proposal includes real-world examples of successful adaptation in clinical care models. It concludes with a summary of the importance and benefits of evolving clinical care models and a future outlook on the evolution of clinical care in response to demographic changes. These proposals are intended to provide a comprehensive overview of the current state and future directions of clinical care models for SCD.
Biology of post-transplant relapse: actionable features
Authors: Orofino Giorgio , Vago Luca 
Published: December 2024

Abstract
In patients receiving allogeneic hematopoietic cell transplantation to cure acute myeloid leukemia (AML), recurrence of the underlying disease, or relapse, represents a crucial unanswered issue and prominent cause of mortality. Still, over recent years, advancements in omic technologies have allowed us to gain new insights into the dynamic changes occurring in cancer and the host over the course of treatments, providing a novel evolutionary perspective on the issue of disease relapse. In this review, we summarize current knowledge on the molecular features of relapsing AML, with a specific focus on changes in the mutational asset of the disease and in the interplay between the tumor and the donor-derived immune system. In particular, we discuss how this information can be translated into relevant indications for monitoring transplanted patients and selecting the most appropriate therapeutic options to prevent and treat relapse.
Maintenance strategies for relapse prevention and treatment
Authors: Geramita Emily , Hou Jing-Zhou , Shlomchik Warren D. , Ito Sawa 
Published: December 2024

Abstract
Posttransplant relapse is the most significant challenge in allogeneic stem cell transplantation (alloSCT). Posttransplant interventions, in conjunction with optimal conditioning regimens and donor selection, are increasingly supported by evidence for their potential to prolong patient survival by promoting antileukemia or graft-versus-leukemia effects. Our review begins by highlighting the current evidence supporting maintenance therapy for relapse prevention in acute myeloid leukemia and acute lymphocytic leukemia. This includes a broad spectrum of strategies, such as targeted therapies, hypomethylating agents, venetoclax, and immunotherapies. We then shift our focus to the role of disease monitoring after alloSCT, emphasizing the potential importance of early detection of measurable residual disease and a drop in donor chimerism. We also provide an overview of salvage therapies for overt relapse, including targeted therapies, chemotherapies, immunotherapies, donor lymphocyte infusion, and selected agents under investigation in ongoing clinical trials. Finally, we review the evidence for a second alloSCT (HSCT2) and discuss factors that impact donor selection for HSCT2.
Hormone-related thrombosis: duration of anticoagulation, risk of recurrence, and the role of hypercoagulability testing
Authors: Scheres Luuk J. J. , Middeldorp Saskia 
Published: December 2024

Abstract
Hormone-related venous thromboembolism (VTE) is common and entails scenarios in which VTE occurs during exposure to exogenous or endogenous female sex hormones, typically estrogen and progestogen. For the management of hormone-related VTE, it is important to realize that many patients use these hormones for a vital purpose often strongly related to the patient's well-being and quality of life. In this review we discuss clinical cases of VTE related to hormonal contraceptive use and pregnancy to illustrate key considerations for clinical practice. We cover practice points for primary VTE treatment and detail the evidence on the risk of recurrent VTE and bleeding in this population. The potential value of thrombophilia testing is described, including “who, why, when, what, and how.” We also discuss key aspects of shared decision-making for anticoagulant duration, including a reduced-dose anticoagulant strategy in hormone-related VTE.
Targeted medical therapies for vascular anomalies
Authors: Borst Alexandra 
Published: December 2024

Abstract
The last 2 decades of genetic discovery in the field of vascular anomalies have brought targeted medical therapies to the forefront of care patients with vascular anomalies and have broadened the role of hematologists/oncologists in this field. Many vascular anomalies have now been identified to be driven by somatic gain-of-function variants in the PI3K/AKT/ mTOR and Ras/MAPK intracellular signaling pathways. This has led to the introduction of various antiangiogenic agents that inhibit these pathways. Knowledge of the indications for and the safe administration of these agents in patients with vascular anomalies is now a crucial part of training for hematologists/oncologists.
In pursuit of a functional cure for follicular lymphoma
Authors: Trotman Judith , Falconer Janlyn 
Published: December 2024

Abstract
We are now a quarter of a century after the transformative impact of rituximab in improving overall survival for patients with follicular lymphoma. With a burgeoning array of effective immunochemotherapy approaches, we can now frame many patients' expectations of longevity and a “functional cure,” with survival estimates for many newly diagnosed patients comparable to age- and gender-matched populations. We highlight not just heterogeneity in disease but also in patients, which influences therapeutic decision-making in an immunochemotherapy era where progression-free survival advances are associated with efficacy-toxicity trade-offs, and no clear overall survival advantage is associated with any specific regimen. We provide the metrics that assist, prognostication both at diagnosis and after initial therapy, but we also highlight the limited long-term follow-up in institutional, population, and clinical trial data sets to inform our survival estimates. Nonetheless, the data are sufficient to empower us to reframe more optimistic conversations with our patients and the lymphoma community, discussions that engender hope and planning for a life lived long, and well, after therapy for follicular lymphoma.
T-cell–based therapies for treating relapsed or refractory mantle cell lymphoma
Authors: Epstein-Peterson Zachary D. , Palomba M. Lia 
Published: December 2024

Abstract
While targeted therapies such as Bruton's tyrosine kinase and BCL2 inhibitors have fundamentally changed the treatment of mantle cell lymphoma (MCL), not all patients respond to these therapies, and responses are finite and can be fleeting, especially with high-risk MCL. As patients progress through successive therapies, the clinical course is characterized by shortening response times,1 frequent disease acceleration, and limited survival outcomes. Recently, the sensitivity of MCL to novel immune-based therapies is being realized with favorable results, as chimeric antigen receptor–modified T cells and bispecific T-cell–engaging antibodies are being investigated and implemented into practice for patients. However, critical issues remain to understand the role of these agents in routine practice. In this review, we discuss the current landscape regarding these agents, examine our approach to incorporating them into practice, and consider unanswered questions that we must ultimately address to improve outcomes for patients.