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New England Journal of Medicine, Volume 392, Issue 17, Page 1698-1709, May 1, 2025.

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New England Journal of Medicine, Ahead of Print.

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New England Journal of Medicine, Ahead of Print.

When a dying patient’s parents refuse to give up hope, her physician opts to hope with them, going to unusual lengths to provide a last treatment he knows will be futile.

This phase 1–2 study involving nine children with leukocyte adhesion deficiency type 1 showed significantly better survival with lentiviral gene therapy without hematopoietic stem-cell transplantation than that in historical controls.

In six families with familial polycythemia, EPO variants led to the production of a hepatic-like erythropoietin that had an altered glycosylation pattern and was more active than the renal form.

Alcohol policy interventions, including those that increase alcohol taxes, raise the drinking and purchase age, reduce days or hours of sale, and impose strong marketing bans, reduce alcohol consumption.

Unhealthy alcohol use is common and includes severe alcohol use disorder. Screening tests identify patients who may benefit from preventive counseling, medications, or more intensive intervention.

The author describes the scientific foundations and implications of a study on variant EPO and erythrocytosis.

A pediatric oncologist’s outlook and practice are transformed when a 10-year-old cricket fanatic with acute lymphoblastic leukemia touches her heart.

A key function of leukocytes is their ability to migrate and extravasate into tissues, which is facilitated by cell surface molecules that promote adhesion to the vascular endothelium. The β2 integrin molecule (also known as CD18) is the common component of four molecular complexes that play a crucial...

Research generally suggests that routine surveillance after cancer treatment finds more recurrences — leading to more surgery, chemotherapy, and radiation — without affecting the risk of death.

Despite greater recognition of the harms of alcohol use, U.S. alcohol taxes are at all-time lows. A reexamination may help inform national debates about revenue generation, spending cuts, and public health.

Relapsed Burkitt’s lymphoma is nearly always fatal. Three patients had a complete metabolic response with the combination of the bispecific antibody glofitamab and the antibody–drug conjugate polatuzumab vedotin.

Neoadjuvant PD-1 blockade with dostarlimab led to organ preservation in a high proportion of patients with early-stage mismatch repair–deficient tumors, with no compromise of surgical options.

Both clonal hematopoiesis of indeterminate potential (CHIP) and cancer are more common with age. When they coexist in the same patient, CHIP cells may migrate to the tumor and have an adverse effect on overall survival.

FcRn protects IgG and albumin from catabolism, transports IgG across the placenta, and regulates IgG function. Blocking or augmenting FcRn can decrease autoimmune antibodies and enhance drug delivery.

Clonal hematopoiesis is the expansion of a genetically related population of hematopoietic stem and progenitor cells that disproportionately contribute to blood-cell production.1 Clonal hematopoiesis of indeterminate potential (CHIP) is defined by mutations in genetic drivers of myeloid cancers, a variant allele fraction of 2% or more, and the...

As the fossil-fuel industry continues to obstruct efforts to curtail pollution from its products, the health community should use strategies that have been effective in fighting other health-harming industries.

In a long-term follow-up study, a single dose of fidanacogene elaparvovec was found to lead to sustained factor IX expression in liver cells and dramatically lowered annualized bleeding rates in 14 patients with hemophilia B.

In January, the FDA proposed substantially limiting the level of nicotine permitted in cigarettes. The proposal is expected to face strong industry opposition during a time of political uncertainty.

A 79-year-old woman was evaluated for cough and weight loss. Chest imaging and thoracentesis findings confirmed the presence of an exudative right pleural effusion. A diagnosis was made.

In a trial involving patients with active cancer and venous thromboembolism, extended anticoagulation with reduced-dose apixaban was noninferior to full-dose apixaban for preventing recurrent thromboembolic events.

The pursuit of rigorous medical science is not compatible with capitulation to government demands aimed at weaponising and eroding science. On April 14, Edwin R Martin Jr, the Trump-appointed interim US attorney for the District of Columbia, sent a letter to at least one medical journal, CHEST, saying “that more and more journals and publications like CHEST Journal are conceding that they are partisans in various scientific debates”. The letter asked the journal to respond to five questions on topics such as how it handles misinformation and different viewpoints.

Reducing the maternal mortality rate due to postpartum haemorrhage depends on the ability of health-care teams to identify pregnant women at higher risk of bleeding, to timely and accurately detect the postpartum haemorrhage event, and to initiate standardised management protocols early on.

Early studies showed that coronary artery bypass grafting (CABG) was superior to percutaneous coronary intervention (PCI) in patients with three-vessel coronary artery disease for survival and event-free survival.1 Since these trials, there have been several advancements in medical therapy, PCI, and CABG. Determining whether a coronary stenosis is flow limiting by visual estimation alone can be subjective; PCI guided by fractional flow reserve (FFR), an objective functional measure of flow-limiting stenoses, has been shown to improve outcomes compared with PCI without FFR.

A decade after the first introduction of angiography-derived fractional flow reserve (FFR), we are now entering an era in which simplified image-derived solutions could replace invasive assessment tools for evaluating coronary lesions. Key advances in the ever-improving contour detection and computational fluid dynamics have enabled angiography-derived FFR to be extensively validated against wire-based FFR in intermediate stenosis (40–90%).1 Angiography-derived FFR offers a non-invasive alternative that reduces wire-related complications, is more logistically feasible, and can be performed repeatedly to optimise percutaneous coronary intervention (PCI).

The 2025 report of the Lancet Countdown to 2030 for women's, children's, and adolescents' health1 assesses global progress and challenges in reproductive, maternal, newborn, child, and adolescent health (RMNCAH) and nutrition, with a focus on sub-Saharan Africa. Global mortality rates related to RMNCAH and nutrition have declined in the past two decades, but progress has slowed since 2015.1 This deceleration has particularly affected sub-Saharan Africa, a trend that is reflected in Senegal's RMNCAH situation.

In The Lancet, we present a concerning picture of progress in improving reproductive, maternal, newborn, child, and adolescent health (RMNCAH) and nutrition, characterised by a marked slowdown since the 2016 launch of the Sustainable Development Goals (SDGs).1 Our analysis in the 2025 report of the Lancet Countdown to 2030 for women's, children's, and adolescents' health1 identifies multiple internal and external threats to progress and highlights the widening gap between sub-Saharan Africa and other regions.

The 2025 European tuberculosis surveillance report underscores the gravity of the situation in the WHO European region.1 Across 53 member states in Europe and Central Asia, more than 225 000 people had tuberculosis in 2023, with 16 000 deaths from the disease.1 Nearly 65 000 cases—or nearly 30%—are thought to be drug-resistant tuberculosis.1 Meanwhile, nine out of 53 WHO member states in the region rank among the world's top 30 high-burden drug-resistant tuberculosis countries.1 Alarmingly, more than half (53%) of Europe's cases of drug-resistant tuberculosis are among previously treated patients, contributing to a quarter of the global burden of drug-resistant tuberculosis.

Six countries, including China, have been banned from key data repositories. Bryant Furlow reports.

The US Food and Drug Administration's new commissioner promises to restore public trust despite mass layoffs. Washington Correspondent Susan Jaffe reports.

In our continuing series on medicine in unusual circumstances, Talha Burki gets a taste of the world of competitive eating.

There are patients you can never forget. Some because you connected unusually deeply with them as people or with their stories—some because you may have seen yourself or a loved one in their shoes, on that gurney, in that pain. On a paediatric rotation as a medical student at Kings County Hospital in East Flatbush, NY, USA, during the 1980s, I was part of team that took care of a toddler slowly succumbing to AIDS. An orphan, as so many were in those terrible years, his bedside chart read Baby M.

Neurologist who developed an integrated model of care for stroke in the UK and saw it become the standard of care nationwide. She was born in Sheffield, UK, on Sept 10, 1956, and died of bowel cancer at home in Wilmslow, UK, on Jan 1, 2025, aged 68 years.

Clinical academia is on a steep decline globally. In the UK, a 6% reduction in the number of clinical academics since 2012 has been reported, with the number of senior lecturer level researchers having decreased by 24%.1 Research is key to evidence-based medicine. Sustainable and progressive change in health research needs to come from within its clinical structure by ensuring full embedment in National Health Service (NHS) core activities.

In early 2025, Taiwan's health-care system faced an unprecedented crisis due to simultaneous outbreaks of influenza and norovirus. The emergency departments had severe overcrowding, which was exacerbated by a shortage of ward beds. A patient died of septic shock after a prolonged 143-km transfer solely for admission to an intensive care unit.1 On Feb 22, 2025, the Taiwan Society of Emergency Medicine issued an urgent statement,2 urging the government to take immediate action. Meanwhile, a government official's dismissive and sarcastic response on social media to an exhausted emergency physician intensified public outrage.

One of the key concerns in the Article by Marco Valgimigli and colleagues is the ambiguity in defining the non-inferiority margin for major adverse cardiovascular or cerebrovascular events (MACCE).1 The study sets a non-inferiority margin of 1·15 for the hazard ratio (HR), which could be considered too lenient given the potential risks associated with de-escalation therapy. A non-inferiority margin of 1·15 means that the study would deem ticagrelor monotherapy acceptable even if it increased the risk of MACCE by 15%.

We read with interest the Article by Marco Valgimigli and colleagues comparing dual antiplatelet therapy (DAPT) de-escalation to ticagrelor monotherapy versus continuing DAPT for 12 months after coronary drug-eluting stent implantation.1 The authors concluded that short-term (<3 months) DAPT and de-escalation to ticagrelor do not increase ischaemic risk and that they reduce the risk of major bleeding. Against this background, we wish to highlight the role of ticagrelor monotherapy in reducing ischaemic complications in patients with diabetes.

I read with great interest the Article by Marco Valgimigli and colleagues.1 The study provides valuable insights into balancing ischaemic protection and bleeding risks, especially in patients with acute coronary syndromes (ACS) and non-ACS. I would like to raise several points for further discussion. First, how did the authors address heterogeneity among patients across different studies, particularly in determining eligibility for de-escalation therapy? Additionally, subgroup analyses between patients with ACS and non-ACS revealed varying outcomes.

We thank our colleagues for their interest in our Article.1 Chunguang Guo and colleagues state that a non-inferiority margin of 1·15 means that the study would deem ticagrelor monotherapy acceptable even if it increased the major adverse cardiovascular or cerebrovascular event (MACCE) risk by 15%.1 This interpretation of the margin fails to consider that the upper 95% CI, not the point estimate, should not cross the margin to reject inferiority. A hazard ratio of 1·00, suggesting identical risks, would have resulted in an upper CI of 1·16 and non-inferiority claim rejection.

We read the Article on the TransMet trial by René Adam and colleagues with great enthusiasm.1 The results are unprecedented, with a staggering 5-year overall survival of 56·6% (95% CI 43·2−74·1) in the liver transplantation plus chemotherapy group compared with 12·6% (5·2–30·1) in the chemotherapy alone group. However, we question whether it is too early to say that the unmet need in patients with unresectable liver-only disease has been addressed.

We read with great interest the results of the TransMet trial1 by René Adam and colleagues showing that the combination of liver transplantation and chemotherapy prolongs survival in patients with colorectal liver metastases and, in some cases, can provide a pathway to cure. We would like to congratulate the authors for their practice-changing trial. We had a few comments regarding its design and some of its results.

We read with great interest the Article on the TransMet trial by René Adam and colleagues.1 This multicentre randomised controlled trial provides robust evidence supporting the benefits of liver transplantation for patients with unresectable colorectal liver metastases, making it an important contribution to the field. We found the study highly valuable; however, a few considerations warrant more discussion.

We thank Akhil Santhosh and colleagues, Dimitrios Moris and colleagues, and Shouhui Yi and colleagues for their positive comments and relevant questions about the practice-changing TransMet trial.1

Strunk T, Molloy EJ, Mishra A, Bhutta ZA. Neonatal bacterial sepsis. Lancet 2024; 404: 277–93—In figure 1 of this Seminar, the teal key title has been updated to “Other neonatal disorders”. This correction has been made to the online version as of April 24, 2025.

Buonfrate D, Ferrari TCA, Adegnika AA, Russell Stothard J, Gobbi FG. Human schistosomiasis. Lancet 2025; 405: 658–70—In this Seminar, Ayola Akim Adegnika's name should have appeared as Prof A A Adegnika in the affiliations. This correction has been made to the online version as of April 24, 2025.

Hu X, Zhang J, Yang S, et al. Angiography-derived fractional flow reserve versus intravascular ultrasound to guide percutaneous coronary intervention in patients with coronary artery disease (FLAVOUR II): a multicentre, randomised, non inferiority trial. Lancet 2025; 405: 1491–504—In this Article, the spelling of author Shengxian Tu's name was incorrect. This correction has been made to the online version as of April 24, 2025, and will be made to the printed version.

Amouzou A, Barros AJD, Requejo J, et al. The 2025 report of the Lancet Countdown to 2030 for women's, children's, and adolescents’ health: tracking progress on health and nutrition. Lancet 2025; 405: 1505–54—In this Review, Abdoulaye Maïga was missing from the author list and his details have been added. These corrections have been made to the online version as of April 24, 2025, and the printed version is correct.

The finding that uterine atony is the commonest cause of postpartum haemorrhage supports the WHO recommendation for all women giving birth to be given prophylactic uterotonics. Knowledge of risk factors with a strong association with postpartum haemorrhage can help to identify women at high risk of postpartum haemorrhage who could benefit from enhanced prophylaxis and treatment. The importance of multiple concurrent causes of postpartum haemorrhage supports the use of treatment bundles.

At the 5-year follow-up, there was no significant difference in a composite outcome of death, stroke, or myocardial infarction after FFR-guided PCI versus CABG, although myocardial infarction and repeat revascularisation were higher with PCI. These results provide contemporary evidence to allow improved shared decision making between physicians and patients.

The angiography-derived FFR-guided comprehensive PCI strategy, encompassing revascularisation decision making and stent optimisation, was non-inferior to intravascular ultrasound guidance. This finding might have implications for future guidelines on its role and application.

In line with previous progress reports by Countdown to 2030 for Women's, Children's, and Adolescents' Health, this report analyses global and regional trends and inequalities in health determinants, survival, nutritional status, intervention coverage, and quality of care in reproductive, maternal, newborn, child and adolescent health (RMNCAH) and nutrition, as well as country health systems, policies, financing, and prioritisation. The focus is on low-income and middle-income countries (LMICs) where 99% of maternal deaths and 98% of child and adolescent deaths (individuals aged 0–19 years) occur, with special attention to sub-Saharan Africa and South Asia.

Access to cancer treatment is not always easy and patients often travel considerable distances for care, especially if living in rural or underserved areas. This journey is not just a matter of distance—it is a journey through layers of crippling cost, disruption, and emotional anguish.

Adoptive cell therapy based on ex-vivo expanded tumor-infiltrating lymphocytes (TILs) has historically been most effective in the treatment of metastatic melanoma,1 with objective response rates of up to 50% and complete responses seen in 20% of patients, even after failure of previous immunotherapy.2,3 However, in other cancer types, particularly those resistant to immune checkpoint inhibitors, the efficacy of TIL therapy remains low, highlighting a major unmet medical need.

Von Hippel-Lindau disease is an autosomal dominant hereditary cancer syndrome, associated with germline inactivating alterations of the VHL gene, and characterised by an increased risk of developing several cancer types, including haemangioblastomas of the CNS and retina, clear cell renal cell carcinoma, pancreatic neuroendocrine tumours, and phaeochromocytomas.1 The historical management of von Hippel-Lindau disease-associated neoplasms resided on surveillance followed by multiple surgical interventions, often burdened by organ function impairment compromising patients’ quality of life.

Using ultrasound guidance and local anaesthesia, prostate tissue sampling can be performed via a transrectal (TRUS) or transperineal (LATP) approach. In the past 5 years, the LATP approach has been promoted due to its proposed advantage of a lower infection risk (by avoiding rectal bacteria) and improved cancer detection. These recommendations were primarily based on low-certainty evidence from observational studies since there was a scarcity of high-quality evidence from randomised, controlled trials (RCTs).

Evidence of the beneficial effect of lung cancer screening by low-dose chest CT scans on lung cancer mortality reduction in a high-risk population continues to grow.1,2 Lung cancer screening has been implemented in several countries, including the USA, where national programmes have been established. In Europe, lung cancer screening is transitioning from research to implementation at varying paces across different countries, with disparities in policy adoption, infrastructure, and funding. The UK is at the forefront of this shift, leading multiple national initiatives.

The successful treatment of patients with cancer has long depended on the capacity to manage infectious complications. Before the late 20th century, treatment failure due to antimicrobial resistance (AMR) was largely recognised to be confined to hospital settings. The emergence of community-associated meticillin-resistant Staphylococcus aureus and the proliferation of extended-spectrum β-lactamase producing Enterobacterales in the early part of the 21st century helped to extend the AMR crisis into community-onset infections.

Detection of tumour-derived DNA fragments in a patient's bodily fluids (circulating tumour DNA [ctDNA]) has been anticipated to revolutionise oncological care for over a decade. Because of its tumour specificity and short half-life (<2 h), ctDNA allows for accurate, real-time monitoring of tumour activity.1 Accordingly, the use of ctDNA to detect post-surgical minimal or molecular residual disease (MRD) was shown to have clinical utility for guiding adjuvant chemotherapy in patients who had surgery for stage II colon cancer.

The global quest to prevent childhood cancer deaths has a long history. For decades, efforts have centred on driving innovation to produce more effective therapies, improve understanding in how and when such therapies should be delivered, and create conditions for optimal care. Through these measures, this quest has been successful in high-income countries (HICs)—many previously fatal conditions are now treatable and survival rates now exceed 80%.1

The decision to abolish NHS England marks a seismic shift in UK health-care governance, ostensibly aimed at cutting bureaucracy and saving approximately £175 million annually but also enhancing ministerial control. This move arrives against the backdrop of an increasingly strained health-care service where “…all parts of the NHS must now live within their means”.1 The economic squeeze has begun, and cancer care will not be immune. Even if additional funding is found and earmarked for cancer services, achieving better outcomes depends on global economic realities.

The rising costs of cancer care are outpacing many other health-care expenditures, underscoring the crucial need to assess the cost-effectiveness of oncological interventions. In this Comment, we reflect on current practices of health-related quality of life (HRQOL) measurement as an essential part of economic evaluations in oncology.

The individual patient data meta-analysis by John Nikitas and colleagues1 provides a valuable exploration of the complex relationship between acute and late toxicity in patients receiving prostate radiotherapy. However, beyond the limitations acknowledged by the authors, several key constraints warrant closer examination.

We read the comments by Zongjian Liang and colleagues with interest. However, we disagree with their overall assessment.

Ryan S Huang and colleagues1 performed a single-arm meta-analysis comparing the efficacy and safety of three ablative therapies to stereotactic body radiotherapy (SBRT) for primary localised renal cell carcinomas (RCCs). However, additional discussion of the methodological approach is necessary before drawing conclusions.

We appreciate the interest shown by Vinson Wai-Shun Chan and colleagues in our article comparing the efficacy and safety of ablative therapies in the management of primary localised renal cell carcinoma (RCC).1 In the absence of direct comparative studies, we believe that a single-arm synthesis remains the best available method for comparing existing evidence. The heterogeneity across studies, while expected due to variations in clinical practice, was transparently reported through I2 values for every meta-analysis,2 and we conducted subgroup analyses to address potential known confounding variables that were significantly associated with local control on meta-regression.

Fennell DA, Ewings S, Ottensmeier C, et al. Nivolumab versus placebo in patients with relapsed malignant mesothelioma (CONFIRM): a multicentre, double-blind, randomised, phase 3 trial. Lancet Oncol 2021; 22: 1530–40—The appendix of this Article has been corrected as of April 30, 2025.

Wang M, Jurczak W, Trneny M, et al. Ibrutinib plus venetoclax in relapsed or refractory mantle cell lymphoma (SYMPATICO): a multicentre, randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol 2025; 26: 200–13—In figure 2 of this Article, the data for age, splenomegaly, and extranodal disease were incorrect and have been amended. These corrections have been made to the online version as of April 30, 2025.

Bhamani A, Creamer A, Verghese P, et al. Low-dose CT for lung cancer screening in a high-risk population (SUMMIT): a prospective, longitudinal cohort study. Lancet Oncol 2025; 26: 609–19—In this Article, Claire Levermore's affiliation should have been “University College London Hospitals NHS Foundation Trust, London, UK”. This correction has been made to the online version as of April 30, 2025, and the printed version is correct.

Pe M, Voltz-Girolt C, Bell J, et al. Using patient-reported outcomes and health-related quality of life data in regulatory decisions on cancer treatment: highlights from an EMA-EORTC workshop. Lancet Oncol 2025; published online April 14. https://doi.org/10.1016/S1470-2045(25)00150-0—In this Essay, the affiliation of Jill Bell should have been Evinova an AstraZeneca Group, Gaithersburg, MD, USA only, and the affiliation of Jan Bogaerts should have been European Organisation for Research and Treatment of Cancer, Brussels, Belgium only.

In February–March, 2025, a Working Group of 20 scientists from 16 countries met at the International Agency for Research on Cancer (IARC) in Lyon, France, to finalise their evaluation of the carcinogenicity of automotive gasoline and some oxygenated gasoline additives.

Pharmaceutical companies are bracing for the US to impose tariffs on its major trading partners, including a 25% tariff on all European products, as part of President Donald Trump's drive to protect and expand key manufacturing sectors in the USA.

On March 21, 2025, Israel demolished the only cancer hospital in Gaza. Footage posted online showed the total destruction of the Turkish–Palestinian Friendship Hospital (TPFH) in what appeared to be a controlled explosion. The Israeli Defence Forces told The Times of Israel that the TPFH was being used by Hamas operatives, but did not provide evidence to support this claim. The hospital ceased functioning in November, 2023. The hospital had been damaged by airstrikes and had run out of fuel after Israel bombarded Gaza in response to the atrocities of Oct 7, 2023, when Hamas-led militants crossed the Israeli border, killed around 1200 people and abducted 251 hostages.

Physicians and scientists have accused the Trump administration of putting cancer research and care at grave risk with massive funding and staff cuts at federal agencies, including 10 000 staff lay-offs announced by the US Health and Human Services Department (HHS).

80 000 people have had their cancer diagnosed or ruled out within 28 days thanks to the UK Government's record £26 billion investment in the National Health Service (NHS).

For many reasons, including sensitivity and stigma surrounding the locations of these cancers, gynaecological cancers are facing a crisis in Australia and globally, with experts describing them as neglected and facing huge funding research shortfalls relative to more common and well-known cancers.

Earlier this month, the National Firefighter Registry (NFR) for Cancer was shut down, following the massive firing of personnel from the US Department of Health and Human Services, the parent agency of the NFR. The registry is a nationwide initiative created by the US Congress that aimed to better understand the link between firefighting and cancer in the USA.

Massive cuts in aid by the USA and other countries have led to 70% of countries reporting disruptions to health services, some of which are comparable to those seen during the COVID-19 pandemic, a WHO assessment has found.

Myung-Ju Ahn has spent her whole career battling sexism. At medical school at Hanyang University in Seoul, South Korea, only 10% of students were female. Once qualified, she faced patients who did not want to be treated by a woman and male peers who dismissed her ability. Even in her choice of specialty she was limited. Surgery and neurology were deemed too demanding for women who were supposed to be taking care of their family and running a household.

When we think about embassies, cancer care rarely comes to mind. Diplomatic missions are traditionally associated with fostering political alliances, issuing visas, or negotiating trade deals. Yet, across Africa, embassies have been quietly stepping into the realm of public health, initiating and supporting projects aimed at combating cancer. Although these efforts have made important contributions, they often fall short of addressing the systemic challenges that perpetuate poor cancer outcomes.

After a career in contemporary dance, a shift to visual arts, and a move from Switzerland to New Zealand, artist Nela Fletcher had won multiple awards for her work. At this point in her life, cancer entered the stage. During her 2022 Esk and Us community art project, she was diagnosed with invasive, grade 2, hormone receptor-positive breast cancer.

These results support the safety and potential antitumour activity of inhibiting the immune checkpoint CISH through the administration of neoantigen-reactive CISH-knockout TILs, with implications for patients with advanced metastatic cancers refractory to checkpoint inhibitor immunotherapies, and provide the first evidence that a novel intracellular checkpoint can be targeted with therapeutic effect.

Updated results support the use of belzutifan as systemic treatment for von Hippel-Lindau disease-associated renal cell carcinoma.

Among biopsy-naive individuals being investigated for possible prostate cancer, biopsy with LATP led to greater detection of GGG 2 or higher disease compared with TRUS. These findings will help to inform patients, clinicians, clinical guidelines, and policy makers regarding the important trade-offs between LATP and TRUS prostate biopsy.

With more than 7 years of follow-up, D-VMP continued to elicit clinical benefits in transplant-ineligible patients with newly diagnosed multiple myeloma, supporting the efficacy and safety of frontline daratumumab-based therapy in this patient population.

Large-scale lung cancer screening is effective and can be delivered efficiently to an ethnically and socioeconomically diverse population.

AMR proportions and IRRs for most key pathogens were up to three-times higher in isolates from outpatients with cancer than those without cancer, highlighting the need for enhanced surveillance, infection prevention, and timely diagnostic stewardship to improve antibiotic prescribing in this population.

Although the null hypothesis could not be rejected, the WSG-KEYRICHED-1 trial highlights the potential of a short chemotherapy-free combination of pembrolizumab with dual anti-HER2 therapy, warranting the initiation of randomised trials investigating the immunotherapy without chemotherapy in patients with HER2-enriched breast cancer.

Droplet digital PCR measurements of ctDNA to assess minimal residual disease before adjuvant targeted therapy and during follow-up can identify patients at high risk of early recurrence. Additional studies using ctDNA measurements to guide therapeutic interventions might lead to improvements in the management of resected stage III melanoma.

These data validate the clinical use of the PSI tool for risk adapted treatment allocation. In patients with PSI 1, the omission of chemotherapy was not associated with excess mortality overall and a distinct better outcome was seen in patients with completed endocrine therapy versus those who had not completed. With completed adjuvant therapy, excess mortality was low for patients with PSI 2, whereas patients with PSI 3–4 had high excess mortality, potentially warranting intensified treatment and requiring further investigation.

Antimicrobial resistance (AMR) is a substantial global health threat. Patients with haematological malignancies have an increased risk of AMR infection due to disease-related and treatment-related immunosuppression. This scoping review searched four bibliographic databases from Jan 1, 2000, to Dec 7, 2023, for publications on AMR bacterial infections in patients with haematological malignancies and identified 274 eligible articles. AMR prevalence data extraction focused on WHO bacterial priority pathogens.

Explanatory clinical trials, which focus on evaluating therapeutic efficacy under ideal circumstances, are crucial for learning about new therapeutic interventions; however, they also exhibit shortcomings. These include non-representative populations and frequent use of intermediate endpoints, leading to uncertainty about the applicability of study results to patients in the real-world. Moreover, these trials often do not address all clinically meaningful questions, highlighting the need for optimisation within the oncology research framework.

This Policy Review summarises an expert Delphi consensus process on larynx-preservation treatments in patients affected by intermediate-to-advanced laryngeal or hypopharyngeal squamous cell carcinoma. The experts, who represented all perspectives involved in multidisciplinary management of these patients and included patient representatives, approved 137 consensus statements that cover several relevant areas in the field of larynx-preserving treatments. Statements are grouped in the following topics: granular indications for T2–T3 cancer, indications for T4a cancer, indications for salvage organ-preservation surgery after chemoradiation failure, laryngeal function at baseline, which comorbidities are contraindications and to what extent, organ preservation in older patients: selection criteria, post-treatment surveillance, prognostic and predictive factors, listening to the patient's preferences: tools and implementation, prehabilitation and rehabilitation protocols, and cost-effectiveness of different laryngeal preservation approaches.

Optimising the use of approved drugs requires evidence from post-approval trials that investigate variations of their use. Determining optimal drug use goes beyond the dominant, academic effort to conduct trials to identify effective lower doses of new drugs. Other important therapeutic approaches that use either less, similar, or more drug than the standard dose need testing in clinical trials, to get the most out of these drugs. Trial objectives on survival outcomes vary greatly; some aim for superiority, others for equivalent exposure or non-inferiority.

The theme for this year's World Haemophilia Day (April 17, 2025), “Access for All: Women and Girls Bleed Too”, sheds light on the unique, and often-overlooked, challenges faced by women and girls with haemophilia. The persistent misconception that haemophilia only affects men and boys, due to its X-linked inheritance pattern, has historically perpetuated the biased notion that all female carriers are asymptomatic, leading to a systematic failure to recognise their need for specialised medical care.

Watchful waiting—also known as active surveillance—is a common approach for asymptomatic, advanced stage follicular lymphoma, based on real-world data1,2 and results from a randomised trial showing no survival benefit with early chemotherapy.3 The first trial comparing watchful waiting with rituximab was published in 2014,4 and now the results of 15 years of follow-up are reported by Michael Northend and colleagues in The Lancet Haematology.5 Patients with asymptomatic, stage II-IV, low tumour burden follicular lymphoma were randomly assigned to watchful waiting, four once-weekly rituximab infusions (rituximab induction group), or rituximab induction followed by 2 years of rituximab maintenance (rituximab maintenance group).

During the past decade, large-scale paediatric investigational programmes have focused on assessing safety and efficacy of direct oral anticoagulants in the treatment of venous thromboembolism in children. These comprehensive programmes encompassed the development of paediatric-specific formulations tailored to all age groups, phase 2 dose-finding pharmacokinetic and pharmacodynamic studies, and completion of phase 3 randomised controlled trials assessing safety and efficacy of direct oral anticoagulants compared with standard care.

BCMA-directed modalities (CAR T cells, T-cell redirecting bispecific antibodies, and antibody–drug conjugates) have markedly improved the survival of patients with multiple myeloma who are exposed or refractory to immunomodulatory drugs, proteasome inhibitors, and CD38-targeting antibodies (triple-class exposed or refractory multiple myeloma). Triple-class exposed patients who have disease relapse following treatment with such BCMA-directed modalities have poor survival outcomes. However, there is increasing evidence that the use of a second T-cell immunotherapy with an alternative target might provide substantial clinical activity in these patients.

Anaemia affects one in four individuals globally, with substantial implications for maternal and child health.1 Maternal anaemia can lead to adverse outcomes such as low birth weight, premature delivery, and increased risk of maternal mortality due to haemorrhage.2 In children, anaemia can impair motor and cognitive development, which could lead to reduced educational opportunities and quality of life in adulthood.3

We sincerely appreciate the thoughtful commentary by Jaap Jan Boelens and Michael Scordo1 on our Review on donor lymphocyte infusion (DLI) after allogeneic haematopoietic cell transplantation.2 We fully agree with their general emphasis, as also outlined by our Review, on the urgent need for an evidence-based approach of DLI. We concur with their primary concern regarding the poor quality of evidence supporting DLI, particularly outside chronic myeloid leukaemia, with the scarcity of high-level evidence (mainly randomised controlled trials) posing a considerable challenge.

Abboud MR, Cançado RD, De Montalembert M, et al. Crizanlizumab with or without hydroxyurea in patients with sickle cell disease (STAND): primary analyses from a placebo-controlled, randomised, double-blind, phase 3 trial. Lancet Haematol 2025; 12: e248–57—In this Article, the labels in figure 2 for the STAND study should have read, “7·5 mg/kg group”, “5·0 mg/kg group”, and “placebo group”. This correction has been made as of April 14, 2025.

Cook JA, Patten PEM, Peckham N, et al. A 3-week pause versus continued Bruton tyrosine kinase inhibitor use during COVID-19 vaccination in individuals with chronic lymphocytic leukaemia (IMPROVE trial): a randomised, open-label, superiority trial. Lancet Haematol 2025; 12: e294–303—In this Article, the affiliation of Paul Moss, Thomas Roberts, Marie Hodges, Adrian M Shields, and Helen M Parry should have been “Department of Immunology and Immunotherapy and School of Infection, Inflammation and Immunology, College of Medicine and Health, University of Birmingham, UK”; and Paul Moss, Shankara Paneesha, and Helen M Parry should have had the affiliation “University Hospitals Birmingham NHS Trust, Birmingham, UK”.

Kiavasch Mohammad Nejad Farid, from Heidelberg University Hospital (Heidelberg, Germany), presented the results of a compassionate use study of the in-house manufactured second-generation BCMA-directed CAR T-cell construct MDC-CAR-BCMA001 in six patients with relapsed or refractory, multiple myeloma and light-chain amyloidosis. At a median follow-up of 13 months the overall response was 83% (five of six), three of which were complete responses and two very good partial responses. After a median follow-up of 12 months, five remained alive and progression-free (median overall survival and progression-free survival not reached), the relapse-free survival rate was 66% (four of six).

The global burden of sickle cell disease is particularly severe in regions with high malaria prevalence. Uganda, with its significant malaria burden, is one of the countries heavily impacted by sickle cell disease. It is estimated that up to 20% of the population carries the sickle cell trait, with the prevalence of sickle cell disease ranging between 0·7% and 0·8%. This translates to approximately 25 000 new cases annually, with up to 80% of children potentially dying before the age of 5 years due to complications related to the disease.

Jeffery Smith

Matthew R Wilson

These mature data with 15 years of follow-up confirm that early rituximab monotherapy substantially delays the need for new treatment for patients with advanced stage, asymptomatic low tumour burden follicular lymphoma, providing an evidence base for its use in this setting and confirming its value for patients who seek to defer or avoid treatment with chemotherapy.

Sequential molecular MRD monitoring, coupled with MRD-guided treatment, did not improve overall survival in the entire study population; however, in the subgroup of patients with baseline NPM1 and FLT3 ITD mutations, we observed a survival benefit for MRD monitoring.

Incidences of recurrent venous thromboembolism and bleeding during extended-phase anticoagulant treatment were low and similar to those observed during acute-phase treatment and adult studies on extended-phase anticoagulant treatment, providing valuable information for clinical practice on extended anticoagulation in children.

Anti-GPRC5D CAR T-cell salvage therapy induced a high response rate, and could be a potential treatment option in relapsed or refractory multiple myeloma patients who have progressed after anti-BCMA CAR T-cell treatment. Further investigations are warranted to establish the long-term efficacy and safety of this therapeutic approach.

Iron deficiency is the most common micronutrient deficiency worldwide. Oral iron is often recommended as first-line treatment, but there is no consensus on the optimal formulation, dosing strategy, or which patients should be treated preferentially with intravenous iron. To address these challenges, the Iron Consortium at Oregon Health & Science University (OHSU) convened an international panel of 26 experts in haematology, primary care, paediatrics, obstetrics, gastroenterology, cancer, and patient advocacy among its members.

Viral hepatitis remains a global health challenge and immune status affects outcomes. In patients with haematological malignancies, including haematopoietic stem-cell transplantation recipients, viral hepatitis can be life-threatening due to the direct effects of the virus or the need to modify or delay chemotherapy. Additionally, haematopoietic stem-cell donors with past or current viral hepatitis infections might transmit the virus to recipients. The growing recognition of hepatitis E virus (HEV), advances in haematological therapies, and the availability of direct-acting antivirals for hepatitis C virus (HCV), led the 2022 9th European Conference on Infections in Leukaemia (ECIL-9) to update the 2013 ECIL-5 guidelines on viral hepatitis.

A 77-year-old woman was admitted to Matsunami General Hospital (Gifu, Japan) with anaemia and thrombocytopenia. Clinical laboratory data showed a white blood cell count of 4300 per μL (normal range 3300–8600 per μL), with the differential including 10% neutrophils, 85% lymphocytes, and 5% monocytes. The patient's haemoglobin concentration was 6·6 g/dL (normal range 11·6–14·8 g/dL), platelet count was 2·6 × 1010 per L (normal range 15·5–34·8 × 1010 per L), serum lactate dehydrogenase concentration was 305 IU/L (normal range 124–222 IU/L), and serum creatinine level was 0·96 mg/dL (normal range 0·46–0·79 mg/dL).

Our findings demonstrate that neighborhood archetypes efficiently account for complex interactions across social and built environment attributes with leukemia survival. The greater effects of neighborhood archetype in pediatric ALL survival, as compared to AML, may be related to the prolonged, outpatient nature of ALL maintenance therapy and the challenges associated with treatment adherence among patients residing in disadvantaged neighborhoods.

The CORE clinical workflow algorithm is feasible and acceptable among women who have newly diagnosed stage I–III breast cancer with plans for surgery as first‐line treatment. CORE was also acceptable among clinic staff.

Testicular and ovarian juvGCTs are clinically distinct entities. Although testicular juvGCTs exclusively present during infancy and have an excellent prognosis, ovarian juvGCTs may arise at any age and constitute potentially aggressive tumors. Centralized reference diagnostics and the establishment of counseling structures for the treatment of patients with ovarian juvGCTs improved prognosis compared with historical groups. The mitotic rate and incomplete surgery were identified as important risk factors in addition to tumor stage and should be considered in the risk‐stratification of therapy.

Overall cancer mortality declined over 20 years, even during the COVID‐19 pandemic. Disruptions in health care use early in the pandemic resulted in incidence declines in 2020, but 2021 incidence returned to prepandemic levels.

Cancer-related studies were among the nearly 6,000 abstracts presented at Digestive Disease Week® (DDW) 2025, including research on artificial intelligence (AI) in patient communication, polyp detection, and colonoscopy prep.

Anal cancer has been steadily increasing in the United States, with the biggest jumps among older women, especially White and Hispanic women, a new study presented at Digestive Disease Week 2025 (Abstract 76) found. According to the investigators, this shift challenges assumptions about high-risk...

The Atrium Health Levine Cancer Institute established a Financial Toxicity Tumor Board in 2019. The board is the first known institutional-level intervention of its kind and functions like a traditional disease-focused multidisciplinary tumor board—with a singular focus on financial distress.

The Association for Clinical Oncology (ASCO) is carefully reviewing the Administration’s Fiscal Year (FY) 2026 “skinny” budget proposal, which was released May 2 and contains significant cuts to federal health agencies under the Department of Health and Human Services (HHS)—notably, a 40% cut to...

In an analysis from the Scandinavian phase III NARLAL2 trial, reported in the Journal of Clinical Oncology, Schytte et al found that fluorodeoxyglucose (FDG)-PET–guided heterogeneously dose-escalated radiotherapy was not associated with greater 6-month toxicity vs standard radiotherapy in...

In the phase IIb ADAGIO trial, reported in the Journal of Clinical Oncology, Liu et al found that the Wee1 inhibitor adavosertib showed some activity in patients with recurrent or persistent uterine serous carcinoma. However, its use was associated with high toxicity rates.

Applications are now being accepted for the 2025 Integrative Oncology Scholars Program and Integrative Oncology Fellows Program at the University of Michigan in Ann Arbor (https://sites.google.com/view/integrative-oncology-scholars-/home). Launched in 2018, the Integrative Oncology Scholars Program ...

Researchers may have uncovered the role of Plasmodium falciparum malaria in the development of Burkitt lymphoma, according to a recent study published by Ariera et al in The Journal of Immunology.

Ruxolitinib may prove to be an effective treatment of parkinsonism arising from ciltacabtagene autoleucel treatment for patients with multiple myeloma, according to the results of a case report published in the Journal of Hematology. The report featured two cases of patients with multiple myeloma...

Investigators have uncovered mixed progress in major cancer risk factors, preventive behaviors, and screenings in the post–COVID-19 pandemic period among adults in the United States, according to a new study published by Bandi et al in Cancer Epidemiology, Biomarkers & Prevention.

Using next-generation DNA sequencing, researchers have identified four specific genes whose mutations are linked to the development and progression of lethal stomach cancers. This could potentially enable practitioners to offer targeted treatments that would spare many patients from unnecessarily...

A 20-year initiative that offered flexible options for colorectal cancer screening at a major integrated health system doubled colorectal cancer screening rates, cut cancer incidence by a third, halved deaths, and brought racial differences in outcomes to nearly zero, according to a study that will ...

A novel chimeric antigen receptor (CAR) T-cell therapy called AIC100, which targets the ICAM-1 protein, demonstrated encouraging responses and an acceptable safety profile in patients with two types of advanced thyroid cancer. Results from a small, first-in-human phase I trial were presented at the ...

A novel artificial intelligence (AI)-based model could accurately classify sarcomas among pediatric patients using digital pathology images alone, according to new findings presented by Thiesen et al at the 2025 American Association for Cancer Research (AACR) Annual Meeting (Abstract 2423/8).

Compared with a placebo gel, an investigational topical BRAF inhibitor (LUT014) was found to improve the symptoms of acneiform rash in patients with colorectal cancer. These phase II clinical trial results were presented by Anisha B. Patel, MD, Associate Professor of Dermatology, Deputy Chair of...

According to the results of a molecularly matched, tumor-agnostic phase II trial, the combination of the PARP inhibitor olaparib and the PD-1 inhibitor pembrolizumab demonstrated antitumor activity with no new safety signals, particularly in patients with BRCA1/2 mutations. Data from this...

A new gene-expression atlas developed using single-cell RNA sequencing data sheds light on how normal hematopoietic cells differentiate and was used to catalog the multiple ways aberrant differentiation can lead to acute myeloid leukemia (AML). Andy G.X. Zeng, PhD, an MD/PhD candidate at the...

Breast cancer deaths among women between the ages of 20 and 49 declined significantly across all breast cancer subtypes and racial/ethnic groups from 2010 to 2020, with marked declines starting after 2016, according to an analysis of data from the Surveillance, Epidemiology, and End Results (SEER)...

Right ventricle (RV) dysfunction is associated with poorer outcomes in heart failure with preserved ejection fraction (HFpEF). Females are more likely to have HFpEF but males have worse prognosis and resting RV function. The contribution of dynamic RV-pulmonary artery (RV-PA) coupling between sex and its impact on peak exercise capacity (VO2) in HFpEF is not known.

A Phase I, single-center investigation demonstrated that 8 weeks of antimycobacterial therapy improved sarcoidosis forced vital capacity (FVC). Safety and efficacy assessments have not been performed in a multicenter cohort.

All aspects of medical education were affected by the Novel Coronavirus Infectious Disease-19 (COVID-19) pandemic. Several challenges were experienced by trainees and programs alike due to the economic repercussions of the pandemic, how social distancing affected the delivery of medical education, testing and interviewing, how the surge of patients affected redeployment of personnel, potential compromise in core training and the overall impact on the wellness and mental health of trainees and educators.

In this meta-analysis of observational studies, RV dysfunction was associated with higher short-term and long-term mortality in sepsis and septic shock.

Legionella is an uncommon cause of CAP, occurring primarily from late spring through early autumn. Testing is uncommon, even among patients with risk factors, and many positive patients failed to receive empiric coverage for LP.

The nS classification could be used to provide a more accurate prognosis in patients with resected NSCLC. The nS is worth taking into consideration when defining nodal category in the forthcoming ninth edition of the staging system.

NLP successfully identified a large cohort with CC. Most patients were identified through NLP alone, rather than diagnoses or medications. NLP improved detection of patients nearly seven-fold, addressing the gap in ability to identify and characterize CC disease burden. Nearly all cases appeared to be managed in primary care. Identifying these patients is important for characterizing treatment and unmet needs.

Pulmonary arterial hypertension (PAH) is a rare disease and much of our understanding stems from single-center studies, which are limited by sample size and generalizability. Administrative data offer an appealing opportunity to inform clinical, research, and quality improvement efforts for PAH. Yet, there is currently no standardized, validated method to distinguish PAH from other subgroups of pulmonary hypertension (PH) within this data source.

A transparent DL algorithm improves on traditional clinical criteria to predict the need for MV in hospitalized patients, including in those with COVID-19. Such an algorithm may help clinicians optimize timing of tracheal intubation, better allocate resources and staff, and improve patient care.

To assess airway and lung parenchymal damage non-invasively in cystic fibrosis (CF), chest MRI has been historically out of the scope of routine clinical imaging due to technical difficulties such as the low proton density and respiratory and cardiac motion. However, technological breakthroughs have recently emerged to dramatically improve lung MRI quality (including signal-to-noise ratio, resolution, speed, contrast). At the same time, novel treatments have changed the landscape of CF clinical care.

Bronchoscopic lung volume reduction with one-way endobronchial valves is a guideline treatment option for patients with advanced emphysema, supported by extensive scientific data. Patients limited by severe hyperinflation, with a suitable emphysema treatment target lobe and with absence of collateral ventilation are the responders to this treatment. Detailed patient selection, a professional treatment performance, and dedicated follow-up of the valve treatment, including management of complications, are key ingredients to success.

Chronic Obstructive Pulmonary Disease (COPD) may cause profound dyspnea, functional impairment, and reduced quality of life. Available pharmacologic therapy provides suboptimal symptom improvement in many patients. Bronchoscopic lung volume reduction (BLVR), achieved with endobronchial valve (EBV) placement, can effectively improve dyspnea and functional status in appropriately selected patients. Operationalizing a safe and effective BLVR program requires appropriate oversight which can be achieved by a BLVR Nurse Coordinator (NC).

Empathy-based, stigma-reducing communication may lead to improved assessments of tobacco use and smoking cessation for patients with smoking-related cancers. These findings support the dissemination and further testing of a new ECS model for training OCPs in best practices for assessment of smoking history and engagement of patients who currently smoke in tobacco treatment delivery.

In clinical practice, reslizumab may have been initiated in response to heavy symptom burden and CAEs. Reslizumab was associated with improved clinical and patient-reported outcomes and significant reductions in asthma-related HRU.

Quantitative emphysema measured on LDCT of the chest can be leveraged to improve lung cancer risk prediction and help diagnose COPD in individuals who currently or formerly smoked undergoing lung cancer screening.

Durable responses to belzutifan in patients with VHL disease

Sacituzumab tirumotecan improves OS in mTNBC

In 2024, the US FDA approved several new agents for the treatment of patients with cancer, including small-molecule inhibitors, immune-checkpoint inhibitors, bispecific antibodies, antibody–drug conjugates and cell and gene therapy products. Areas of regulatory focus included the accelerated approval programme and diligent completion of post-marketing trials, convening of Oncologic Drugs Advisory Committee meetings to ensure transparent discussions of complex regulatory issues, and continuation of robust, meaningful engagement with the oncology community to foster efficient drug development.

The development of companion diagnostic assays enabling the detection and quantification of HER2 expression and ERBB2 amplifications has provided an important early example that has informed the development of many companion diagnostics for the identification of other drug targets. However, the introduction of trastuzumab deruxtecan and, potentially, other novel antibody–drug conjugates has created the need for assays that are much more sensitive. In this Review, the authors describe the historical development of HER2 companion diagnostic assays in breast and other HER2-positive cancers and highlight the possible, future, more sensitive methods of HER2 detection and quantification that might provide the next generation of companion diagnostics.

Multiple myeloma is a malignancy at the forefront of measurable residual disease (MRD) assessment. In this Review, the authors describe the evolution of MRD analysis in multiple myeloma from technical and clinical standpoints, and discuss opportunities and challenges for MRD-guided management of this disease.

Tumours with deficient DNA mismatch repair (dMMR) leading to a microsatellite instability-high (MSI-H) phenotype are characterized by a high burden of immunogenic mutations and, thus, an immunological ‘hot’ microenvironment that is associated with high sensitivity to immune-checkpoint inhibitors. In this Review, the authors discuss the epidemiology, biology, pathogenesis, clinical diagnosis and treatment of MSI-H/dMMR tumours, highlighting idiosyncrasies associated with specific pathogenetic alterations and tumour histologies.

Surrogate end points in drug regulation are thought to reduce the time required to bring new drugs to market; however, only a few of the drugs approved on the basis of these outcomes have subsequently demonstrated robust improvements in overall survival (OS). If the FDA and other regulators were to shift their priority to patient-centred outcomes, such as OS, I argue that such a shift would probably lead to fewer, but also a higher standard of drugs entering the market, potentially with faster approval decisions because novel therapies would initially be tested in later lines and in patients with a worse prognosis.

Stereotactic radiosurgery (SRS) has been established as a key therapeutic modality for the management of brain metastases. In this Review, an international group of experts discuss the expanding opportunities for SRS, including application for larger brain metastases and cumulative intracranial tumour volumes, fractionated delivery, neoadjuvant use and combinatorial approaches with modern systemic therapy, as well as associated challenges and remaining questions.

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No abstract available

No abstract available

Resistance to cytarabine is a key problem in the treatment of acute myeloid leukemia (AML). To understand the molecular biology of resistance to cytarabine, a viability-based chemosensitizer screen was utilized. We screened synthetic lethal targets using 437 different small interfering RNAs (siRNAs) directed against factors involved in DNA repair mechanisms and cytarabine as the chemical compound. Three hits were identified: CUL4A, TP73, and RFC2. We show here that the ubiquitin ligase CULLIN 4A (CUL4A) and the tumor-suppressive transcription factor p73 contribute to drug resistance by modulating DNA damage response. P73 confers resistance to cytarabine therapy by transactivation of REV3L, encoding the catalytic subunit of translesion DNA polymerase ζ, and CUL4A probably by influencing proliferating cell nuclear antigen (PCNA) and the polymerase switch towards error-prone translesion DNA polymerases. Abrogation of the polymerase ζ by siRNA causes identical effects as siRNAs against CUL4A or TP73 and resensitizes cells towards cytarabine therapy in vitro. As CUL4A needs to be activated by neddylation to facilitate the degradation of several proteins including PCNA, we propose a novel explanation for the synergism between cytarabine and the neddylation inhibitor pevonedistat by inhibition of translesion synthesis. In keeping with this, in AML patients treated with cytarabine, we found high expression of CUL4A and TP73 to be associated with poor prognosis.

Data on outcome of patients with mantle cell lymphoma (MCL) and COVID-19 infection are limited. The European MCL (EMCL) registry is a centralized registry of the EMCL network, collecting real-world information about treatments and disease courses. During the COVID-19 pandemic, additional data on MCL patients with COVID-19 infection were collected, aiming to identify risk factors for mortality from COVID-19. In our retrospective, multicenter, international study, we collected data from 63 MCL patients with a median age of 64 years (range, 44–84) in 9 countries with evidence of a COVID-19 infection between February 2020 and October 2021. The overall mortality rate was high (44.4%), especially in hospitalized patients (61%) and in patients with need for intensive care unit care (94%). Patients receiving rituximab had significantly poorer survival than patients not receiving rituximab (P = 0.04). Our data highlight the importance of prevention strategies and underline the need for effective vaccination in this vulnerable cohort.

Immune dysregulation has been highlighted as a key player in the pathogenesis of myelodysplastic syndromes (MDS), but little is known about cytokine profiles in patients with unexplained cytopenia with or without mutations in MDS-associated genes (clonal cytopenias of undetermined significance [CCUS] and idiopathic cytopenias of undetermined significance [ICUS], respectively), which often precede MDS. Here, we study the cytokine profiles in 111 patients with ICUS (N = 41), CCUS (N = 30), lower-risk MDS (LR-MDS; N = 22) and higher-risk MDS (HR-MDS; N = 18), and in healthy elderly controls (N = 21). Twenty cytokines were examined in blood plasma at time of diagnosis using Luminex assays and enzyme linked immunosorbent assays. The cytokine levels were compared between patient groups, and in patients versus controls. Associations between cytokines and MDS-associated mutations were evaluated. An aberrant cytokine profile was observed in all patient groups relative to healthy elderly controls. Patients had significantly higher levels of IL-6 (P< 0 .001), tumor necrosis factor α (P < 0.001), IL-10 (P < 0.001), and C-X-C motif chemokine 10 (P < 0.001) and lower levels of transforming growth factor beta 1 (P < 0.001), CCL5/regulated on activation normal T-cell expressed and secreted (P < 0.001), and S100A4 (P < 0.001) compared with healthy controls. Survival was significantly shorter in CCUS and MDS patients with a high systemic inflammatory cytokine load (median overall survival [OS] 21 months) compared with those with low-moderate systemic inflammatory cytokine load (median OS 64 months; P < 0.0001). These data suggest that patients with ICUS and CCUS have cytokine levels as abnormal as in LR-MDS. Indeed, high cytokine levels are present before MDS is diagnosed and cytokine levels are elevated irrespective of the presence or size of the myeloid clones. Cytokines may have a prognostic impact at a very early premalignant stage of myeloid disorders.

No abstract available

No abstract available

Musculoskeletal symptoms in chronic graft-versus-host disease (cGVHD) are rare manifestations contributing to disease burden. This study assesses the frequency of muscle cramps, joint and muscle aches, and muscle weakness in a cohort of patients severely affected by cGVHD. Three hundred thirty-four patients participated in the NCI natural history study of cGVHD (NCT00092235) from October 2004 to March 2017. Five-point Lee cGVHD Symptom Scale was dichotomized (less symptom bother—0, 1, 2; severe symptom bother—3, 4) and tested for associations with: Short Form 36 (SF36), 2-minute walk test, grip strength, joint range of motion, and human activity profile, clinical and laboratory data. Seventy-five point four percent of patients reported joint and muscle aches (36.8% severe, Lee Symptom Scale score 3–4), 74.3% muscle cramps (33.5% severe), and 82.34% muscle weakness (45.51% severe), which were associated with reduced functional capacity (SF36 Physical Component Scale, P < 0.0001). Muscle cramps were associated with limited joint movement (P < 0.0001) and skin manifestations (skin thickening, P = 0.0008; itchy skin, P = 0.0003). Muscle cramps did not show association with potential causative agents, such as concomitant calcineurin inhibitors therapy, statins, or use of antidiabetic drugs. Joint and muscle aches showed associations with multiple variables (including strong associations with mood symptoms and fatigue, P < 0.0001). Muscle weakness was not associated with steroid dose, but was significantly associated with depression (P < 0.0001) and anxiety (P = 0.0009). This study documents a high frequency of musculoskeletal symptoms in a cohort of adult patients with cGVHD. The multivariable logistic regression models showed that a joint set of factors were moderately well associated with musculoskeletal symptoms in this study.

No abstract available

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Drug resistance and treatment failure in pediatric acute lymphoblastic leukemia (ALL) are in part driven by tumor heterogeneity and clonal evolution. Although bulk tumor genomic analyses have provided some insight into these processes, single-cell sequencing has emerged as a powerful technique to profile individual cells in unprecedented detail. Since the introduction of single-cell RNA sequencing, we now have the capability to capture not only transcriptomic, but also genomic, epigenetic, and proteomic variation between single cells separately and in combination. This rapidly evolving field has the potential to transform our understanding of the fundamental biology of pediatric ALL and guide the management of ALL patients to improve their clinical outcome. Here, we discuss the impact single-cell sequencing has had on our understanding of tumor heterogeneity and clonal evolution in ALL and provide examples of how single-cell technology can be integrated into the clinic to inform treatment decisions for children with high-risk disease.

Real-world data on the efficacy and tolerability of isatuximab with pomalidomide and dexamethasone (IsaPomDex) in relapsed/refractory myeloma patients have not been reported. In this UK-wide retrospective study, IsaPomDex outcomes were evaluated across 24 routine care cancer centers. The primary endpoint was overall response rate (ORR). Secondary endpoints included progression-free survival (PFS), duration of response (DOR) for patients who achieved an objective response (≥partial response [PR]), and adverse events (AEs). In a total cohort 107 patients, median follow up (interquartile range [IQR]) was 12.1 months (10.1–18.6 mo), median age (IQR) was 69 years (61–77). Median (IQR) Charlson Comorbidity Index (CCI) score was 3 (2–4); 43% had eGFR <60 mL/min. Median (IQR) number of prior therapies was 3 (3–3). Median (IQR) number of IsaPomDex cycles administered was 7 (3–13). ORR was 66.4%, with responses categorized as ≥ very good partial response: 31.8%, PR: 34.6%, stable disease: 15.9%, progressive disease: 15%, and unknown 2.8%. Median PFS was 10.9 months. Median DOR was 10.3 months. There was no statistical difference in median PFS by age (<65: 10.2 versus 65–74 13.2 versus ≥75: 8.5 mo, log-rank P = 0.4157), by CCI score (<4: 10.2 mo versus ≥4: 13.2, log-rank P = 0.6531), but inferior PFS was observed with renal impairment (≥60: 13.2 versus <60: 7.9 mo, log-rank P = 0.0408). Median OS was 18.8 months. After a median of 4 cycles, any grade AEs were experienced by 87.9% of patients. The most common ≥G3 AEs were neutropenia (45.8%), infections (18.7%), and thrombocytopenia (14%). Our UK-wide IsaPomDex study demonstrated encouraging efficacy outcomes in the real world, comparable to ICARIA-MM trial.

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The hierarchical framework of the adult blood system as we know it from current medical and hematology textbooks, displays a linear branching network of dividing and differentiated cells essential for the growth and maintenance of the healthy organism. This view of the hierarchy has evolved over the last 75 years. An amazing increase in cellular complexity has been realized; however, innovative single-cell technologies continue to uncover essential cell types and functions in animal models and the human blood system. The most potent cell of the hematopoietic hierarchy is the hematopoietic stem cell. Stem cells for adult tissues are the long-lived self-renewing cellular component, which ensure that differentiated tissue-specific cells are maintained and replaced through the entire adult lifespan. Although much blood research is focused on hematopoietic tissue homeostasis, replacement and regeneration during adult life, embryological studies have widened and enriched our understanding of additional developmental hierarchies and interacting cells of this life-sustaining tissue. Here, we review the current state of knowledge of the hierarchical organization and the vast heterogeneity of the hematopoietic system from embryonic to adult stages.

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It has been unclear what role metabolism is playing in the pathophysiology of chronic lymphocytic leukemia (CLL). One reason is that the study of CLL metabolism is challenging due to the resting nature of circulating CLL cells. Also, it is not clear if any of the genomic aberrations observed in this disease have any impact on metabolism. Here, we demonstrate that CLL cells in proliferation centers exhibit upregulation of several molecules involved in glycolysis and mitochondrial metabolism. Comparison of CXCR4/CD5 intraclonal cell subpopulations showed that these changes are paralleled by increases in the metabolic activity of the CXCR4lowCD5high fraction that have recently egressed from the lymph nodes. Notably, anti-IgM stimulation of CLL cells recapitulates many of these metabolic alterations, including increased glucose uptake, increased lactate production, induction of glycolytic enzymes, and increased respiratory reserve. Treatment of CLL cells with inhibitors of B-cell receptor (BCR) signaling blocked these anti-IgM-induced changes in vitro, which was mirrored by decreases in hexokinase 2 expression in CLL cells from ibrutinib-treated patients in vivo. Interestingly, several samples from patients with 17p-deletion manifested increased spontaneous aerobic glycolysis in the unstimulated state suggestive of a BCR-independent metabolic phenotype. We conclude that the proliferative fraction of CLL cells found in lymphoid tissues or the peripheral blood of CLL patients exhibit increased metabolic activity when compared with the bulk CLL-cell population. Although this is due to microenvironmental stimulatory signals such as BCR-engagement in most cases, increases in resting metabolic activity can be observed in cases with 17p-deletion.

The rapid evolution of genomic technologies over the last years has led to the development of different methods for the detection, measurement and analysis of cell-free DNA fragments (cfDNA) which are shed into the bloodstream by apoptotic cells and circulate at a low concentration in plasma. In cancer patients, the proportion of tumor-derived cfDNA is defined as circulating tumor DNA. This analysis, commonly known as liquid biopsy, allows to access tumor DNA through a simple blood sampling and therefore without the need of an invasive tissue biopsy. For this reason, this tool may have several clinical applications in terms of diagnosis, prognosis, and monitoring of minimal residual disease. However, there are still several critical issues that need to be resolved. In this review, we will discuss some of the controversies around this method and its potential clinical applications.

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Genotyping is not routinely performed at diagnosis of von Willebrand disease (VWD). Therefore, the association between genetic variants and pathogenic mechanism or the clinical and laboratory phenotype is unknown in most patients, especially in type 1 VWD. To investigate whether genotyping adds to a better understanding of the pathogenic mechanisms and variability in phenotype, we analyzed the VWF gene in 390 well-defined VWD patients, included in the WiN study. A VWF gene variant was found in 155 patients (61.5%) with type 1, 122 patients (98.4%) with type 2, and 14 patients (100%) with type 3 VWD. Forty-eight variants were novel. For each VWF gene variant, the pathogenic mechanisms associated with reduced VWF levels was investigated using the FVIII:C/VWF:Ag and VWFpp/VWF:Ag ratios. In type 1 VWD, reduced synthesis or secretion of VWF was most frequently found in patients with nonsense variants, frameshift variants, and deletions, whereas rapid clearance of VWF was mainly found in patients with missense variants. Furthermore, type 1 VWD patients with and without a VWF gene variant were clearly distinct in their clinical features such as age of diagnosis, laboratory phenotype, and bleeding phenotype. In type 2 VWD, 81% of variants were associated with an increased clearance of VWF. To conclude, we identified the pathogenic mechanisms associated with various VWF gene variants in type 1, 2, and 3 VWD patients. Additionally, major differences in the phenotype of type 1 VWD patients with and without a variant were observed, which may be of importance for clinical management.

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Measurable residual disease (MRD) quantified by multiparameter flow cytometry (MFC) is a strong and independent prognostic factor in acute myeloid leukemia (AML). However, several technical factors may affect the final read-out of the assay. Experts from the MRD Working Party of the European LeukemiaNet evaluated which aspects are crucial for accurate MFC-MRD measurement. Here, we report on the agreement, obtained via a combination of a cross-sectional questionnaire, live discussions, and a Delphi poll. The recommendations consist of several key issues from bone marrow sampling to final laboratory reporting to ensure quality and reproducibility of results. Furthermore, the experiences were tested by comparing two 8-color MRD panels in multiple laboratories. The results presented here underscore the feasibility and the utility of a harmonized theoretical and practical MFC-MRD assessment and are a next step toward further harmonization.

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Mastocytosis is a hematologic neoplasm characterized by expansion and focal accumulation of neoplastic mast cells (MC) in diverse organs, including the skin, bone marrow (BM), spleen, liver, and gastrointestinal tract. The World Health Organization classification divides the disease into prognostically distinct variants of cutaneous mastocytosis (CM) and systemic mastocytosis (SM). Although this classification remains valid, recent developments in the field and the advent of new diagnostic and prognostic parameters created a need to update and refine definitions and diagnostic criteria in MC neoplasms. In addition, MC activation syndromes (MCAS) and genetic features predisposing to SM and MCAS have been identified. To discuss these developments and refinements in the classification, we organized a Working Conference comprised of experts from Europe and the United States in August 2020. This article reports on outcomes from this conference. Of particular note, we propose adjustments in the classification of CM and SM, refinements in diagnostic criteria of SM variants, including smoldering SM and BM mastocytosis (BMM), and updated criteria for MCAS and other conditions involving MC. CD30 expression in MC now qualifies as a minor SM criterion, and BMM is now defined by SM criteria, absence of skin lesions and absence of B- and C-findings. A basal serum tryptase level exceeding 20 ng/mL remains a minor SM criterion, with recognition that hereditary alpha-tryptasemia and various myeloid neoplasms may also cause elevations in tryptase. Our updated proposal will support diagnostic evaluations and prognostication in daily practice and the conduct of clinical trials in MC disorders.

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This expert opinion originally developed by a panel of the Italian Society of Thalassemias and Hemoglobinopathies (SITE), reviewed and adopted by the European Hematology Association (EHA) through the EHA Scientific Working Group on Red Cells and Iron, has been developed as priority decision-making algorithm on evidence and consensus with the aim to identify which patients with transfusion-dependent beta-thalassemia (TDT) could benefit from a gene therapy (GT) approach. Even if the wide utilized and high successful allogeneic hematopoietic stem-cell transplantation provides the possibility to cure several patients a new scenario has been opened by GT. Therefore, it is important to establish the patients setting for whom it is priority indicated, particularly in the early phase of the diffuse use outside experimental trials conducted in high selected centers. Moreover, actual price, limited availability, and resources disposal constitute a further indication to a rational and progressive approach to this innovative treatment. To elaborate this algorithm, the experience with allogeneic transplantation has been used has a predictive model. In this large worldwide experience, it has been clearly demonstrated that key for the optimal transplant outcome is optimal transfusion and chelation therapy in the years before the procedure and consequently optimal patient’s clinical condition. In the document, different clinical scenarios have been considered and analyzed for the possible impact on treatment outcome. According to the European Medicine Agency (EMA) for the GT product, this expert opinion must be considered as a dynamic, updatable, priority-based indications for physicians taking care of TDT patients.

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As a result of significant recent developments, the management of patients with chronic lymphocytic leukemia (CLL) is changing, and new therapeutic options will continue to emerge in the near future. The recommendations of the French Innovative Leukemia Organization (FILO-CLL) group presented here are intended to provide practical recommendations for physicians taking care of CLL patients, taking into account the availability of both biological tests and therapies in daily practice in France at the time of publication. This text details the documented information and guidelines on diagnosis, indications for treatment, infectious complications and therapeutic strategies in frontline and relapsed CLL as well as in particular conditions such as autoimmune cytopenia or Richter syndrome.

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Infections are a major cause of morbidity and mortality in patients with chronic lymphocytic leukemia (CLL). These can be exacerbated by anti-leukemic treatments. In addition, the typical patients with CLL already have fragilities and background risk factors that apply to the general population for severe COVID-19. On these bases, patients with CLL may experience COVID-19 morbidity and mortality. Recurrent seasonal epidemics of SARS-CoV-2 are expected, and doctors taking care of patients with CLL must be prepared for the possibility of substantial resurgences of infection and adapt their approach to CLL management accordingly. In this Guideline Article, we aim at providing clinicians with a literature-informed expert opinion on the management of patients with CLL during SARS-CoV-2 epidemic.

In the light of the COVID-19 pandemic, the International Workshop on Waldenström Macroglobulinemia (IWWM) Treatment Recommendations Panel felt the need to provide a consensus statement for the management of Waldenström Macroglobulinemia (WM) patients during this challenging time. We followed the current recommendations by the American Society of Hematology, which have been modified accordingly to fit the specific realities associated with the management of WM. In this Consensus Statement, the Panel addresses questions related to treatment initiation, preferred therapies, minimizing visit to clinics and infusions centers, supportive care and guidance for WM patients in clinical trials. Finally, we also provide information on timing and appropriateness of testing and management of COVID-19 infected patients, as well as ways to get physicians and patients involved in registry studies that could help others.

The objective of this guideline is to aid clinicians in making individual salvage treatment plans for pediatric and adolescent patients with first relapse or refractory (R/R) classical Hodgkin lymphoma (cHL). While salvage with standard dose chemotherapy followed by high dose chemotherapy and autologous stem cell transplant is often considered the standard of care in adult practice, pediatric practice adopts a more individualized risk stratified and response adapted approach to salvage treatment with greater use of non-transplant salvage. Here, we present on behalf of the EuroNet Pediatric Hodgkin Lymphoma group, evidence and consensus-based guidelines for standardized diagnostic, prognostic and response procedures to allocate children and adolescents with R/R cHL to stratified salvage treatments.

Myeloid neoplasms (MNs) with germline predisposition have recently been recognized as novel entities in the latest World Health Organization (WHO) classification for MNs. Individuals with MNs due to germline predisposition exhibit increased risk for the development of MNs, mainly acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Setting the diagnosis of MN with germline predisposition is of crucial clinical significance since it may tailor therapy, dictate the selection of donor for allogeneic hematopoietic stem cell transplantation (allo-HSCT), determine the conditioning regimen, enable relevant prophylactic measures and early intervention or contribute to avoid unnecessary or even harmful medication. Finally, it allows for genetic counseling and follow-up of at-risk family members. Identification of these patients in the clinical setting is challenging, as there is no consensus due to lack of evidence regarding the criteria defining the patients who should be tested for these conditions. In addition, even in cases with a strong suspicion of a MN with germline predisposition, no standard diagnostic algorithm is available. We present the first version of the Nordic recommendations for diagnostics, surveillance and management including considerations for allo-HSCT for patients and carriers of a germline mutation predisposing to the development of MNs.

Healthy subjects frequently report minor bleedings that are frequently ‘background noise’ of normality rather than a true disorder. Nevertheless, unexpected or unusual bleeding may be alarming. Thus, the distinction between normal and pathologic bleeding is critical. Understanding the underlying pathologic mechanism in patients with an excessive bleeding is essential for their counseling and treatment. Most of these patients with significant bleeding will result affected by non-severe inherited bleeding disorders (BD), collectively denominated mild or moderate BD for their relatively benign course. Unfortunately, practical recommendations for the management of these disorders are still lacking due to the current state of fragmented knowledge of pathophysiology and lack of a systematic diagnostic approach. To address this gap, an International Working Group (IWG) was established by the European Hematology Association (EHA) to develop consensus-based guidelines on these disorders. The IWG agreed that grouping these disorders by their clinical phenotype under the single category of mild-to-moderate bleeding disorders (MBD) reflects current clinical practice and will facilitate a systematic diagnostic approach. Based on standardized and harmonized definitions a conceptual unified framework is proposed to distinguish normal subjects from affected patients. The IWG proposes a provisional comprehensive patient-centered initial diagnostic approach that will result in classification of MBD into distinct clinical-pathological entities under the overarching principle of clinical utility for the individual patient. While we will present here a general overview of the global management of patients with MBD, this conceptual framework will be adopted and validated in the evidence-based, disease-specific guidelines under development by the IWG.

Chronic myelomonocytic leukemia (CMML) is a disease of the elderly, and by far the most frequent overlap myelodysplastic/myeloproliferative neoplasm in adults. Aside from the chronic monocytosis that remains the cornerstone of its diagnosis, the clinical presentation of CMML includes dysplastic features, cytopenias, excess of blasts, or myeloproliferative features including high white blood cell count or splenomegaly. Prognosis is variable, with several prognostic scoring systems reported in recent years, and treatment is poorly defined, with options ranging from watchful waiting to allogeneic stem cell transplantation, which remains the only curative therapy for CMML. Here, we present on behalf of the European Hematology Association and the European LeukemiaNet, evidence- and consensus-based guidelines, established by an international group of experts, from Europe and the United States, for standardized diagnostic and prognostic procedures and for an appropriate choice of therapeutic interventions in adult patients with CMML.

On April 23, 2025, the Food and Drug Administration approved penpulimab-kcqx (Akeso Biopharma Co., Ltd.) with cisplatin or carboplatin and gemcitabine for the first-line treatment of adults with recurrent or metastatic non-keratinizing nasopharyngeal carcinoma (NPC).

On April 11, 2025, the Food and Drug Administration approved nivolumab (Opdivo, Bristol Myers Squibb Company) with ipilimumab (Yervoy, Bristol Myers Squibb Company) for the first-line treatment of adult patients with unresectable or metastatic hepatocellular carcinoma (HCC).

On April 8, 2025, the Food and Drug Administration approved nivolumab (Opdivo, Bristol Myers Squibb Company) with ipilimumab (Yervoy, Bristol Myers Squibb Company) for adult and pediatric patients 12 years of age and older with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer (CRC). The FDA also converted the accelerated approval to regular approval for single agent nivolumab for adult and pediatric patients 12 years of age and older with MSI-H or dMMR metastatic CRC, that has progressed following fluoropyrimidine, oxaliplatin, and irinotecan.

On March 28, 2025, the Food and Drug Administration approved durvalumab (Imfinzi, AstraZeneca) with gemcitabine and cisplatin as neoadjuvant treatment, followed by single agent durvalumab as adjuvant treatment following radical cystectomy, for adults with muscle invasive bladder cancer (MIBC).

On March 28, 2025, the Food and Drug Administration expanded the indication for lutetium Lu 177 vipivotide tetraxetan (Pluvicto, Novartis Pharmaceuticals Corporation) to include adults with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor pathway inhibitor (ARPI) therapy and are considered appropriate to delay taxane-based chemotherapy.

On March 26, 2025, the Food and Drug Administration approved cabozantinib (Cabometyx, Exelixis, Inc.) for adult and pediatric patients 12 years of age and older with previously treated, unresectable, locally advanced or metastatic, well-differentiated pancreatic neuroendocrine tumors (pNET) and well-differentiated extra-pancreatic neuroendocrine tumors (epNET). 

On March 19, 2025, the Food and Drug Administration granted traditional approval to pembrolizumab (Keytruda, Merck) with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 (CPS ≥1).

On February 14, 2025, the Food and Drug Administration approved vimseltinib (Romvimza, Deciphera Pharmaceuticals, LLC), a kinase inhibitor, for adult patients with symptomatic tenosynovial giant cell tumor (TGCT) for which surgical resection will potentially cause worsening functional limitation or severe morbidity.

On February 11, 2025, the Food and Drug Administration approved brentuximab vedotin (Adcetris, Seagen Inc., a subsidiary of Pfizer) in combination with lenalidomide and a rituximab product for adult patients with relapsed or refractory large B-cell lymphoma (LBCL), including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS), DLBCL arising from indolent lymphoma, or high-grade B-cell lymphoma (HGBL), after two or more lines of systemic therapy who are ineligible for autologous hematopoietic stem cell transplantation (auto-HSCT) or CAR T-cell therapy.

On February 11, 2025, the Food and Drug Administration approved mirdametinib (Gomekli, SpringWorks Therapeutics, Inc.), a kinase inhibitor, for adult and pediatric patients 2 years of age and older with neurofibromatosis type 1 (NF1) who have symptomatic plexiform neurofibromas (PN) not amenable to complete resection.

On January 21, 2025, the Food and Drug Administration approved treosulfan (Grafapex, medac GmbH), an alkylating agent, with fludarabine as a preparative regimen for allogeneic hematopoietic stem cell transplantation (alloHSCT) in adult and pediatric patients 1 year of age and older with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS).

On January 27, 2025, the Food and Drug Administration approved fam-trastuzumab deruxtecan-nxki (Enhertu, Daiichi Sankyo, Inc.) for unresectable or metastatic hormone receptor (HR)-positive, HER2-low (IHC 1+ or IHC 2+/ISH-) or HER2-ultralow (IHC 0 with membrane staining) breast cancer, as determined by an FDA-approved test, that has progressed on one or more endocrine therapies in the metastatic setting.

On January 17, 2025, the Food and Drug Administration approved datopotamab deruxtecan-dlnk (Datroway, Daiichi Sankyo, Inc.), a Trop-2-directed antibody and topoisomerase inhibitor conjugate, for adult patients with unresectable or metastatic, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative (IHC 0, IHC1+ or IHC2+/ISH-) breast cancer who have received prior endocrine-based therapy and chemotherapy for unresectable or metastatic disease.

On January 16, 2025, the Food and Drug Administration approved sotorasib (Lumakras, Amgen Inc.) with panitumumab (Vectibix, Amgen Inc.) for adult patients with KRAS G12C-mutated metastatic colorectal cancer (mCRC), as determined by an FDA-approved test, who have received prior fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy. 

On January 16, 2025, the Food and Drug Administration granted traditional approval to acalabrutinib (Calquence, AstraZeneca) with bendamustine and rituximab for adults with previously untreated mantle cell lymphoma (MCL) who are ineligible for autologous hematopoietic stem cell transplantation (HSCT).

On December 27, 2024, the Food and Drug Administration approved nivolumab and hyaluronidase-nvhy (Opdivo Qvantig, Bristol Myers Squibb Company) for subcutaneous injection across approved adult, solid tumor nivolumab (Opdivo, Bristol Myers Squibb Company) indications as monotherapy, monotherapy maintenance following completion of Opdivo plus Yervoy (ipilimumab) combination therapy, or in combination with chemotherapy or cabozantinib.

On December 20, 2024, the Food and Drug Administration granted accelerated approval to encorafenib (Braftovi, Array BioPharma Inc., a subsidiary of Pfizer Inc.) with cetuximab and mFOLFOX6 for patients with metastatic colorectal cancer (mCRC) with a BRAF V600E mutation, as detected by an FDA-approved test.

On December 18, 2024, the Food and Drug Administration approved remestemcel-L-rknd (Ryoncil, Mesoblast, Inc.), an allogeneic bone marrow-derived mesenchymal stromal cell (MSC) therapy, for steroid-refractory acute graft versus host disease (SR-aGVHD) in pediatric patients 2 months of age and older. Ryoncil is the first FDA-approved MSC therapy.

On December 18, 2024, the Food and Drug Administration approved ensartinib (Ensacove, Xcovery Holdings, Inc.) for adult patients with anaplastic lymphoma kinase (ALK)-positive locally advanced or metastatic non-small cell lung cancer (NSCLC) who have not previously received an ALK-inhibitor.

On December 13, 2024, the Food and Drug Administration approved cosibelimab-ipdl (Unloxcyt, Checkpoint Therapeutics, Inc.), a programmed death ligand-1 (PD-L1) blocking antibody, for adults with metastatic cutaneous squamous cell carcinoma (mCSCC) or locally advanced CSCC (laCSCC) who are not candidates for curative surgery or curative radiation. 

On December 4, 2024, the Food and Drug Administration approved durvalumab (Imfinzi, AstraZeneca) for adults with limited-stage small cell lung cancer (LS-SCLC) whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy.

On November 20, 2024, the Food and Drug Administration granted accelerated approval to zanidatamab-hrii (Ziihera, Jazz Pharmaceuticals, Inc.), a bispecific HER2-directed antibody, for previously treated, unresectable or metastatic HER2-positive (IHC 3+) biliary tract cancer (BTC), as detected by an FDA-approved test.

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