Seminars in hematology最新文献

Novartis, a global medicines company, and the Sickle Cell Foundation of Ghana (SCFG), an advocacy organization, have endeavored to support the implementation of global best practices in the care of people living with sickle cell disease (SCD) in Africa, and to address unmet needs relating to this condition on the continent. Beginning in 2019, a multifaceted SCD program was implemented in Ghana through a public-private partnership involving the government of Ghana, the SCFG, Novartis, and other partners. A key component of the program involved expanding the reach of hydroxyurea (HU), the only approved disease-modifying generic treatment for SCD, in ways that would promote sustainable access. The program helped to raise the profile of SCD in Ghana and, in 2022, the government adopted HU into its National Health Insurance Scheme. Features of the effort in Ghana are now being expanded to other countries in Africa through cocreated programs with in-country partners. This article reviews the program's history, progress, challenges, and lessons learned.

Natural killer (NK)/T-cell lymphomas (NK/TCL) and peripheral T-cell lymphomas (PTCL) are aggressive hematological malignancies. With the development of next-generation sequencing, circulating tumor DNA (ctDNA) can be detected by several techniques with clinical implications. So far, the effect of ctDNA in pretreatment prognosis prediction, longitudinal monitoring of treatment response and surveillance of long-term remission or relapse in NK/TCL and PTCL has been reported in several researches.

Large B-cell lymphomas (LBCLs) are a strikingly diverse set of diseases, including clinical, biological, and molecular heterogeneity. Despite a wealth of information resolving this heterogeneity in the research setting, applying molecular features routinely in the clinic remains challenging. The advent of circulating tumor DNA (ctDNA) liquid biopsies promises to unlock additional molecular information in the clinic, including mutational genotyping, molecular classification, and minimal residual disease detection. Here, we examine the technologies, applications, and studies exploring the utility of ctDNA in LBCLs.

Indolent B-cell lymphomas are generally incurable with standard therapy and most patients have a prolonged disease course that includes multiple treatments and periods of time in which they do not require therapy. Currently available tools to monitor disease burden and define response to treatment rely heavily on imaging scans that lack tumor specificity are unable to detect disease at the molecular level. Circulating tumor DNA (ctDNA) is a versatile and promising biomarker being developed across multiple lymphoma subtypes. Advantages of ctDNA include high tumor specificity and limits of detection that are significantly lower than imaging scans. Potential clinical applications of ctDNA in indolent B-cell lymphomas include baseline prognostication, early signs of treatment resistance, measurements of minimal residual disease, and a noninvasive method to directly monitor disease burden and clonal evolution after therapy. Clinical applications of ctDNA have not yet proven clinical utility but are increasingly used as translational endpoints in clinical trials testing novel approaches and the analytic techniques used for ctDNA continue to evolve. Advances in therapy for indolent B-cell lymphomas include novel targeted agents and combinations that achieve very high rates complete response which amplifies the need to improve our current methods to monitor disease.

Liquid biopsies utilizing plasma circulating tumor DNA (ctDNA) are anticipated to revolutionize decision-making in cancer care. In the field of lymphomas, ctDNA-based blood tests represent the forefront of clinically applicable tools to harness decades of genomic research for disease profiling, quantification, and detection. More recently, the discovery of nonrandom fragmentation patterns in cell-free DNA (cfDNA) has opened another avenue of liquid biopsy research beyond mutational interrogation of ctDNA. Through examination of structural features, nucleotide content, and genomic distribution of massive numbers of plasma cfDNA molecules, the study of fragmentomics aims at identifying new tools that augment existing ctDNA-based analyses and discover new ways to profile cancer from blood tests. Indeed, the characterization of aberrant lymphoma ctDNA fragment patterns and harnessing them with powerful machine-learning techniques are expected to unleash the potential of nonmutant molecules for liquid biopsy purposes. In this article, we review cfDNA fragmentomics as an emerging approach in the ctDNA research of B-cell lymphomas. We summarize the biology behind the formation of cfDNA fragment patterns and discuss the preanalytical and technical limitations faced with current methodologies. Then we go through the advances in the field of lymphomas and envision what other noninvasive tools based on fragment characteristics could be explored. Last, we place fragmentomics as one of the facets of ctDNA analyses in emerging multiview and multiomics liquid biopsies. We pay attention to the unknowns in the field of cfDNA fragmentation biology that warrant further mechanistic investigation to provide rational background for the development of these precision oncology tools and understanding of their limitations.