Poly(ADP-ribose) polymerase inhibitors (PARPi) have profoundly transformed the management of patients with cancer, particularly ovarian cancer patients. However, their use is associated with hematologic toxicities, ranging from transient cytopenias to myeloid neoplasia post-cytotoxic therapy (MN-pCT). Transient cytopenias, mainly anemia, occur early after treatment initiation and display a variable profile depending on the PARPi, with a central role of PARP2 inhibition in erythropoietic abnormalities. More rarely, MN-pCT develop after prolonged exposure to PARPi and are associated with an unfavorable prognosis, characterized by complex cytogenetic abnormalities and high-risk mutations, particularly TP53. Current data suggest a mechanism of selection of pre-existing clonal hematopoiesis under the selective pressure of cytotoxic therapies followed by PARPi. A better understanding of the pathophysiological mechanisms and early identification of high-risk patients could enable optimized monitoring puis des PARPi. Une meilleure compr & eacute;hension des m & eacute;canismes physiopathologiques et l'identification pr & eacute;coce des patients & agrave; risque pourraient permettre d'optimiser la surveillance et, potentiellement, de d & eacute;velopper des approches pr & eacute;ventives visant & agrave; limiter ces complications h & eacute;matologiques. and, potentially, the development of preventive approaches to limit the development of MN-pCT.
Transcranial Doppler (TCD) has been used routinely since the 1990s in children with sickle cell disease SS/Sb0 from the age of 2, enabling the detection of children risk of clinical stroke. Abnormally high cerebral velocities (>= 200 cm/s) expose children to a 40% risk of stroke within three years. This risk has been reduced to 2% thanks the implementation of a transfusion program. However, the risk of silent infarction, known to cause cognitive impairment, remained high at 37% before the age of 14. More recent investigations of the extracranial cervical portion of the internal carotid artery have shown a highly significant association between high velocities (>= 160 cm/s), the visibility of stenosis on magnetic resonance angiography (MRA), and an increased risk of silent infarction. The systematic detection of this cervical arteriopathy Doppler ultrasound and MRA since 2011, combined with the implementation of a transfusion program, has significantly reduced the risk of silent infarcts. Hydroxyurea, which significantly reduces crises, acute chest syndromes, and hemolysis, also reduces the risk of abnormal velocities, but its introduction after the age of 2 has not reduced the risk of silent infarction, and its effect on the development of cerebral vasculopathy remains to be evaluated. The management of abnormal velocities and intracranial cervical stenoses that have occurred despite hydroxyurea is based on a transfusion program and hematopoietic stem cell transplantation.
Hospital at home (HaH) is playing an increasing role in oncology and hematology care pathways, in a context marked by rising cancer incidence, the chronic nature of malignant hematologic diseases, and the expansion of injectable therapies. The current model, still largely hospital-centered, faces organizational limitations that support the development of hybrid models of care. The impact of cancer and its treatments on patients' quality of life remains substantial, highlighting the need to improve coordination between hospital and community care. In this context, HaH emerges not only as an alternative mode of treatment administration but also as a lever for organizational transformation. French experiences with the externalization of systemic anticancer drug treatments in oncology and hematology show that home administration is feasible and safe, provided that it relies on a robust structure: shared protocols; close coordination between hospital teams, HaH services, and community healthcare professionals; secure pharmaceutical logistics; and appropriate training of providers. The gradual integration of innovative therapies, such as bispecific antibodies, further supports the relevance of hybrid pathways combining hospital-based care with home-based treatment delivery. For patients, HaH reduces travel, supports remaining at home, and improves continuity of care. For the healthcare system, it contributes to smoother care pathways, reduces pressure on day hospitals, and supports the transition toward more outpatient and territorially integrated oncology care.
The field of transcriptomics has undergone two relatively recent revolutions compared to the early discoveries about the genetic information contained within our cells. First, single-cell RNA sequencing (scRNA-seq) has enabled a better characterization of tissue and tumor microenvironments, confirming what was already known: Tissue heterogeneity cannot be accurately assessed through bulk transcriptomic analysis. The second revolution involves studying gene expression linked to spatial information. As of this writing, a quick search of the NCBI database using the keywords "spatial," "transcriptomics," and "cancer" yields over 3,000 articles published since 2016, the year this method was introduced to the scientific community. These techniques have been crucial for understanding the tumor microenvironment in various cancers. Improvements in these methods suggest an exponential growth in publications, similar to the trajectory observed with scRNA-seq. Without being exhaustive, this review highlights the impact of spatial transcriptomics on the understanding of certain hematologic malignancies and its clinical relevance.
Erythropoietin (EPO) is a key hormone regulating erythropoiesis, whose production is tightly controlled by oxygen availability. While the kidney is the main source of EPO in adulthood, the liver plays a major role during fetal development and retains the capacity to express EPO under certain pathological conditions. This review summarizes the physiological and molecular bases of EPO regulation, the main sites of its production throughout life, as well as the mechanisms involved in hypoxia pathway-related secondary erythrocytosis. Particular emphasis is placed on the recent identification of mutations in non-coding regions of the EPO gene associated with familial erythrocytosis. These mutations lead to increased EPOtranscription in a model of immature hepatic cells and to the production of circulating EPO displaying a hepatic-like glycosylation profile and enhanced biological activity. Together, these findings broaden the spectrum of mechanisms responsible for erythrocytosis and highlight the importance of qualitative EPO analyses, in addition to genetic and quantitative approaches, to improve diagnosis and understanding of these disorders.
