bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clonal Hematopoiesis of Indeterminate Potential Does Not Impact Overall Survival in Multiple Myeloma
Authors: Rexha Farah , Gustine Joshua , Han Ryan , Nakamoto-Matsubara Rie , Panaroni Cristina , Shome Rajib , Nardi Valentina , Branagan Andrew R. , Cirstea Diana , Yee Andrew J. , Raje Noopur 
Published: December 2024

Introduction:
Clonal hematopoiesis of indeterminate potential (CHIP) is frequently observed in patients with multiple myeloma (MM). A previous study demonstrated that CHIP is associated with shorter progression-free survival in MM patients undergoing autologous stem cell transplantation (ASCT), particularly those who do not receive maintenance therapy with an immunomodulatory agent (Mouhieddine Nat Commun 2020). We sought to further characterize the impact of CHIP on overall survival (OS) in a large cohort of MM patients, as well as the risk of developing a myeloid neoplasm.
Methods:
Study participants include MM patients evaluated at the Massachusetts General Hospital between January 2019 and December 2022 who underwent targeted exome sequencing (i.e., Heme SNaPshot) on DNA extracted from unselected bone marrow for CHIP-associated somatic mutations. CHIP was defined by the presence of a leukemia-associated mutation with a variant allele fraction &gt;2% in unselected bone marrow aspirate samples. Medical records were manually reviewed for all patients to extract data on baseline clinical characteristics and survival outcomes. Time-to-event outcomes were estimated using the Kaplan-Meier method, and comparisons were made with the log-rank test. Cox-proportional hazard regression analyses were performed to fit univariate and multivariate models for OS; the outcome measure was hazard ratio (HR) with 95% confidence interval (CI). OS was defined as the time from CHIP diagnosis to death or last follow-up. Cumulative incidence estimates for myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) were made with the Fine-Gray method to account for death as a competing risk. Only patients who consented to mutational testing were included in this analysis and does not represent all consecutive MM patients seen at our institution.
Results:
A total of 317 patients with MM underwent gene sequencing, of whom 167 (53%) had CHIP. By univariate analysis, patients with CHIP had a significantly shorter median OS (4.2 years versus not reached; p&lt;0.001). However, on multivariate analysis, CHIP was not associated with OS (HR 1.40, 95% CI 0.83-2.38; p=0.21) after adjusting for age, sex, time from MM diagnosis, tumor burden, extramedullary disease, high-risk cytogenetics, R-ISS, prior therapy, albumin, LDH, and beta-2 microglobulin level. Four patients (1.3%) developed MDS/AML in this cohort, of whom 3 out of 4 patients (75%) had CHIP. Between patients with and without CHIP, there was no statistical difference in the risk of developing MDS/AML after both the diagnosis of MM and time of mutational testing when accounting for death as a competing risk (Fine-Gray p=0.49 and p=0.33, respectively).
Conclusion:
The presence of CHIP is not associated with OS and does not appear to be associated with risk of myeloid neoplasms in MM patients.
Cardiovascular Outcome of Heart Failure Patients with Iron Deficiency Anemia Who Received Iron Infusion Vs Red Blood Cell Transfusion: Analysis from a Nationwide Trinetx Database
Authors: Elom Hilary A , Kulasekaran Monika , Adeniran Lanre , Ilonze Onyedika J 
Published: December 2024

Background: Heart Failure (HF) is a significant global health burden, and Iron deficiency anemia (IDA) can worsen outcomes in HF. About 30-50% of HF patients are reported to have IDA, commonly due to nutritional deficiencies, gastrointestinal loss, impaired absorption, and chronic inflammatory cytokines present in HF. HF guidelines recommend IV iron to reduce HF hospitalization. This study aims to evaluate the cardiovascular outcome of HF patients with IDA treated with iron infusion vs RBC transfusion.
Methods: A nationwide retrospective cohort study was conducted using the TriNetX platform, analyzing adult HF patients with IDA from 2015 to 2023. The intervention cohort 1 received iron infusions without packed RBCs, while the control cohort 2 received packed RBCs without iron infusions. Cardiovascular and cerebrovascular outcomes, ICU admissions, and mortality were assessed from 1-month post-intervention. Cohorts were matched 1:1 using Propensity Score Matching (PSM) based on demographics, cardiovascular risk factors, chronic medical conditions, and nutritional status to minimize confounding variables in comparing the two treatment modalities.
Results: After propensity score matching, a total of 20,862 study participants were included in each study cohort. The mean age of cohort 1(patients who received iron infusion with no blood transfusion) and cohort 2(those who received RBC transfusion with no iron infusion were 69.2 +/- 15.0 and 69.3 +/-14.5 respectively. Majority of the patients were White (68%) and female (55%) in both cohorts. Patients in cohort 1 were 20 % less likely to have unstable angina, PCI/coronary angioplasty and acute myocardial ischemia compared with cohort 2 (OR 0.80; 95% CI 0.74 - 0.86). Myocardial infarctions were less likely to occur in patients in cohort 1 (OR 0.71; 95% CI 0.66 - 0.76) compared with patients in cohort 2. Additionally, Patients in Cohort 1 also demonstrated a significantly lower odd of composite cerebrovascular disease (stroke, TIA, carotid intervention/angioplasty) (OR 0.45; 95% CI 0.46 - 0.54) compared to those in cohort 2. The analysis further revealed a significant association with ICU admission (aOR 0.011; 95% CI 0.07 - 0.19) and mortality (aOR 0.99; 95% CI 0.287 - 0.312).
Conclusion: HF patients with IDA receiving iron infusion without RBC transfusion exhibited significantly lower risks of composite adverse cardiovascular and cerebrovascular outcomes compared to those receiving RBC transfusion without iron infusion. This supports IV iron's benefit in HF, reducing ICU hospitalization, mortality and adverse composite outcomes.
Mutations and MRD: clinical implications of clonal ontogeny
Authors: Radich Jerald 
Published: December 2024

Abstract
Measurable residual disease (MRD) is a strong but imprecise predictor of relapse in acute myeloid leukemia. Many patients fall into the outlier categories of MRD positivity without relapse or MRD negativity with relapse. Why? We will discuss these states in the context of “clonal ontogeny” examining how mutations, clonal structure, and Darwinian rules impact response, resistance, and relapse.
Catastrophic antiphospholipid syndrome: a CAPS-tivating hematologic disease
Authors: Salter Brittany M. , Crowther Mark Andrew 
Published: December 2024

Abstract
Catastrophic antiphospholipid syndrome (CAPS) is a rare but life-threatening form of antiphospholipid syndrome (APS) defined by the rapid onset of large and small vessel thrombosis occurring simultaneously across multiple sites, resulting in multiorgan dysfunction. The presence of underlying immune dysfunction causing activation of coagulation and, in many cases, abnormal complement regulation predisposes these patients to thrombotic events. CAPS is often preceded by triggering factors such as infection, surgery, trauma, anticoagulation discontinuation, and malignancy. Given the high mortality rate, which may exceed 50%, prompt recognition and initiation of management is required. The detection of antiphospholipid antibodies and the histopathologic identification of microvascular ischemia via tissue biopsy are required to diagnose CAPS. However, these patients are often too unwell to obtain results and wait for them. As such, investigations should not delay CAPS therapy, especially if there is strong clinical suspicion. Management of CAPS requires “triple therapy” with glucocorticoids, intravenous heparin, therapeutic plasma exchange, and/or intravenous immunoglobulin. Treatment for refractory disease is based on poor-quality evidence but includes anti-CD20 (rituximab) or anticomplement (eculizumab) monoclonal antibodies and other immunosuppressant agents, either alone or in combination. The rarity of this syndrome and the subsequent lack of randomized clinical trials have led to a paucity of high-quality evidence to guide management. Continued international collaboration to expand ongoing CAPS registries will allow a better understanding of the response to newer targeted therapy.
Treatment of VTE in the thrombocytopenic cancer patient
Authors: Moik Florian , Ay Cihan 
Published: December 2024

Abstract
Thrombocytopenia is a frequent complication in patients with cancer, mostly due to the myelosuppressive effects of antineoplastic therapies. The risk of venous thromboembolism (VTE) in patients with cancer is increased despite low platelet counts. The management of cancer-associated VTE in patients with thrombocytopenia is challenging, as the risk of both recurrent VTE and bleeding complications is high. Moreover, the time-dependent nature of thrombocytopenia over the course of antineoplastic therapies further complicates the management of patients in clinical practice. In the absence of evidence from high-quality studies, the management of anticoagulation therapy for VTE must be personalized, balancing the individual risk of VTE progression and recurrence against the risk of hemorrhage. In the present case-based review, we highlight the clinical challenges that arise upon managing cancer-associated VTE in the setting of present or anticipated thrombocytopenia, summarize the available evidence, and provide a comparative overview of available guidelines.
Anticoagulation at the end of life: whether, when, and how to treat
Authors: Parks Anna L. 
Published: December 2024

Abstract
Nearly 2 out of 3 patients with venous thromboembolism (VTE) and 1 out of 4 patients with atrial fibrillation (AF) will die within the year. Whether, when, and how to manage anticoagulation at the end of life requires many trade-offs. Patients and clinicians must balance symptom burden, greatly elevated bleeding and thrombosis risks, competing comorbidities and medications, and changing goals over time. This review uses cases of VTE and AF to present a framework for care that draws upon existing disease-specific data and cutting-edge palliative care science. It reviews strategies for the difficult task of estimating a patient's prognosis, characterizes the enormous public health burden of anticoagulation in serious illness, and analyzes the data on anticoagulation outcomes among those with limited life expectancy. Finally, an approach to individualized decision-making that is predicated on patients' priorities and evidence-based strategies for starting, continuing, or stopping anticoagulation at the end of life are presented.
Diagnosis and management of hereditary hemochromatosis: lifestyle modification, phlebotomy, and blood donation
Authors: Girelli Domenico , Marchi Giacomo , Busti Fabiana 
Published: December 2024

Abstract
The term hemochromatosis refers to a group of genetic disorders characterized by hepcidin insufficiency in the context of normal erythropoiesis, iron hyperabsorption, and expansion of the plasma iron pool with increased transferrin saturation, the diagnostic hallmark of the disease. This results in the formation of toxic non–transferrin-bound iron, which ultimately accumulates in multiple organs, including the liver, heart, endocrine glands, and joints. The most common form is HFE-hemochromatosis (HFE-H) due to p.Cys282Tyr (C282Y) homozygosity, present in nearly 1 in 200 people of Northern European descent but characterized by low penetrance, particularly in females. Genetic and lifestyle cofactors (especially alcohol and dysmetabolic features) significantly modulate clinical expression so that HFE-H can be considered a multifactorial disease. Nowadays, HFE-H is mostly diagnosed before organ damage and is easily treated by phlebotomy, with an excellent prognosis. After iron depletion, maintenance phlebotomy can be usefully transformed into a blood donation program. Lifestyle changes are important for management. Non-HFE-H, much rarer but highly penetrant, may lead to early and severe heart, liver, and endocrine complications. Managing severe hemochromatosis requires a comprehensive approach optimally provided by consultation with specialized centers. In clinical practice, a proper diagnostic approach is paramount for patients referred for hyperferritinemia, a frequent finding that reflects hemochromatosis only in a minority of cases.
Pegylated interferon: the who, why, and how
Authors: Kiladjian Jean-Jacques 
Published: December 2024

Abstract
Interferon alpha (IFN-α) is a fascinating molecule with many biological properties yet to be fully understood. Among these properties, several have demonstrated usefulness for targeting malignant cells, including hematopoietic cells from patients with myeloproliferative neoplasms. Indeed, IFN-α has been used for decades across all myeloproliferative neoplasms, but only recently a new form, ropegIFN-α2b, was approved to treat patients with polycythemia vera. Many phase 2 and more recently phase 3 studies have demonstrated IFN-α's promise in treating patients with essential thrombocythemia and early-stage myelofibrosis. In addition, although not approved in that situation, IFN-α is the only cytoreductive therapy that can be used during pregnancy. Today, IFN-α is a key medicine for polycythemia vera and essential thrombocythemia, while its place in the management of myelofibrosis must be better defined. The advantages of IFN therapy include a well-known safety profile, high rates of clinical and molecular responses, and a unique ability to deeply reduce the mutant allele burden of most of the driver mutations causing myeloproliferative neoplasms. Recent preliminary data from prospective studies suggest that molecular responses may be correlated with prolonged event-free survival, raising the hope that IFN therapy may ultimately alter the natural history of many diseases.
Novel conditioning and prophylaxis regimens for relapse prevention
Authors: Mancusi Antonella , Ruggeri Loredana , Pierini Antonio 
Published: December 2024

Abstract
The last 20 years witnessed relevant clinical advancements in the field of hematopoietic cell transplantation (HCT) for leukemia patients. The introduction of novel conditioning regimens, a better prophylaxis and management of graft- versus-host disease, and an ameliorated posttransplant support system improved safety and, therefore, outcomes. On the other hand, leukemia relapse remains the major cause of allogeneic HCT failure. Efforts have been made to understand the mechanisms of leukemia relapse, and new insights that clarify how donor immunity exerts graft-versus- leukemia (GVL) activity are available. Such studies set the base to design novel transplant strategies that can improve disease control. In our review we begin by discussing the most relevant criteria to choose a donor that provides a strong GVL effect. We also report some of the novel conditioning regimens that aim to deliver and extend myeloablation in order to reduce the disease burden at time of graft infusion. Finally, we discuss how the graft can be manipulated to limit the use of immune suppression and ensure potent antileukemic activity.
On the horizon: upcoming new agents for the management of ITP
Authors: Lambert Michele P. 
Published: December 2024

Abstract
Treatment of immune thrombocytopenia (ITP) has evolved over the last 20 years in response to our increased understanding of the pathophysiology of this complex immune disorder. New treatments in development have taken advantage of our evolving understanding of the biology of this disease to target new mechanisms and expand the available ways in which to approach patients with this disorder. This review focuses on novel therapeutics in the ITP pipeline and discusses the pathophysiology of ITP that has led to their development.
Risk-stratification in frontline CLL therapy: standard of care
Authors: Tausch Eugen , Schneider Christof , Stilgenbauer Stephan 
Published: December 2024

Abstract
The treatment of chronic lymphocytic leukemia (CLL) has been transformed over the past decade based on a better understanding of disease biology, especially regarding molecular genetic drivers and relevant signaling pathways. Agents focusing on B-cell receptor (in particular Bruton tyrosine kinase [BTK]) and apoptosis (BCL2) targets have replaced chemoimmunotherapy (CIT) as the treatment standard. BTK and BCL2 inhibitor−based therapy has consistently shown prolonged progression-free survival and in some instances even increased overall survival against CIT in frontline phase 3 trials. This improvement is particularly pronounced in high-risk CLL subgroups defined by unmutated IGHV, deletion 17p (17p−), and/or the mutation of TP53, making CIT in these subgroups essentially obsolete. Despite remarkable advances, these markers also retain a differential prognostic and predictive impact in the context of targeted therapies, mandating risk-stratification in frontline management. Furthermore, BTK- and BCL2-targeting agents differ in their adverse event profiles, requiring adjustment of treatment choice based on patient characteristics such as coexisting conditions, comedications, and delivery-of-care aspects.
Your chemo is no good here: management of high-risk MCL
Authors: Sawalha Yazeed , Maddocks Kami 
Published: December 2024

Abstract
Historically considered a lymphoma with limited treatment options and poor outcomes, the treatment landscape in mantle cell lymphoma (MCL) has evolved remarkably in the last decade. Chemoimmunotherapy (CIT) remains the primary frontline treatment for most patients with MCL, typically with an intensive approach in younger and fit patients. The role of consolidative autologous stem cell transplantation remains controversial, with recent data further questioning its benefit. Novel agents have shown promising results in recent frontline clinical trials and challenge the current paradigm in MCL, particularly in high-risk patients who generally have poor outcomes with CIT. Risk stratification is key to incorporating novel agents in the frontline treatment of MCL, identifying patients who do not benefit from or could be spared CIT, guiding treatment intensity and duration, and improving overall outcomes, including safety and quality of life. The MCL International Prognostic Index and Ki-67 play an important role in identifying patients with high-risk MCL. TP53 aberrations, particularly mutations, currently identify patients with the highest risk, limited benefit from CIT, and greatest need for novel therapies. Other genetic aberrations and biological clusters are being identified but currently have limited clinical utility.
Quantifying menorrhagia and overview of nonsurgical management of heavy menstrual bleeding
Authors: Wheeler Allison P. , Hemingway Celeste O. 
Published: December 2024

Abstract
Heavy menstrual bleeding (HMB) is a common problem, presenting in 1 in 5 females. The quantification of menstrual blood loss and the subsequent treatment of HMB are both nuanced tasks that require the physician to consider the patient perspective. The individualization of care and transition to methods that fit each individual patient are critical to building a successful relationship with the patient to facilitate follow-up care and evaluation of response to treatment. In this review we outline various methods of quantification of menstrual blood loss, including considerations of accuracy and practicality. These methods, all of which have the potential for clinical benefit, vary from pictorial assessment charts to the gold standard alkaline hematin method to asking the patient about their average amount of blood loss and how it affects their quality of life. Next, we outline nonsurgical treatments for HMB, including hormonal and nonhormonal options, and consider the potential for success, as well as treatment considerations and contraindications. Overall, options for the evaluation and nonsurgical management of menstrual blood loss and HMB are presented along with quality-of-life considerations.
The POD24 challenge: where do we go from here for early progressors?
Authors: Mondello Patrizia , Casulo Carla 
Published: December 2024

Abstract
Follicular lymphoma is the most common indolent lymphoma, with a favorable prognosis and survival measured in decades. However, approximately 15% to 20% of patients encounter early disease progression, termed POD24, within 24 months from diagnosis or treatment initiation. Recognizing the correlation between POD24 and a heightened risk of lymphoma-related death has sparked intensive investigations into the clinical and biological determinants of POD24 and the development of innovative treatment strategies targeting this group. Research is also ongoing to understand the varying impact of POD24 based on different clinical contexts and the implications of early histologic transformation on POD24 prognosis. Recent investigations have uncovered potential new predictors of POD24, including genetic and nongenetic alterations as well as some conflicting F-fludeoxyglucose–positron emission tomography characteristics such as maximum standardized uptake value and total metabolic tumor volume. These developments, together with clinical predictors, have led to the emergence of several clinicopathologic tools to help identify at diagnosis patients who may be at higher risk for POD24. As these models are not routinely used, more work is needed to develop new risk-stratification strategies integrating clinical and molecular risk profiling that can be easily implemented in clinical practice to drive therapeutic choice. This review aims to delineate the modest but incremental progress achieved in our understanding of POD24, both clinically and biologically. Furthermore, we offer insights into the best practices to approach POD24 in the current era, aspiring to chart a new path forward to optimize patient outcomes.
Neurological manifestations of MGUS
Authors: Cibeira M. Teresa , Rodríguez-Lobato Luis Gerardo , Alejaldre Aida , Fernández de Larrea Carlos 
Published: December 2024

Abstract
Monoclonal gammopathy of undetermined significance (MGUS) is a highly prevalent disorder characterized by a small bone marrow plasma cell or lymphoplasmacytic clone (less than 10%) that produces a small amount of monoclonal paraprotein without associated organ damage. Most patients with MGUS display benign behavior indefinitely, but some progress to an overt malignancy, and others develop organ damage despite no increase in monoclonal protein, resulting in the so-called MG of clinical significance (MGCS). This concept includes different disorders depending on the organ involved, and among them, MG of neurological significance (MGNS) constitutes a real challenge from both a diagnostic and therapeutic point of view. Diagnosis is particularly difficult due to MGNS's heterogeneous clinical presentation and common lack of a diagnostic biopsy. On the other hand, the complexity of treatment lies in the lack of standardized regimens and the common irreversibility of neurological damage. Focusing on the neurological manifestations of MGUS affecting the peripheral nervous system, we describe 3 illustrative cases from daily practice and discuss different aspects of diagnosis to treatment, emphasizing the need for multidisciplinary management based on the close collaboration of neurologists and hematologists.