Allogeneic hematopoietic cell transplantation (HCT) in patients with myelodysplastic syndrome (MDS) improves overall survival. The authors evaluated the impact of MDS genetics on the benefit of HCT in a biological assignment (donor v no donor) study. https://pubmed.ncbi.nlm.nih.gov/37607457/ ALSO AS VIDEO ON https://youtu.be/JbHS_-2sJQc CONNECT WITH US https://twitter.com/TheEBMT_Trainee https://www.ebmt.org/trainee-committee https://twitter.com/CarmeloGurnari
In this study, Nathanial and colleagues systematically analyzed CD19 CAR-T cells of 10 children with R/R B-ALL enrolled in the CARPALL trial via high-throughput single-cell gene expression and T cell receptor sequencing of infusion products and serial blood and bone marrow samples up to 5 years after infusion. Article: https://www.nature.com/articles/s41591-023-02415-3
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Chimeric antigen receptor (CAR) T-cell therapy is a promising option for patients with heavily treated multiple myeloma. Point-of-care manufacturing can increase the availability of these treatments worldwide. Aina and colleagues assessed the safety and activity of ARI0002h, a BCMA-targeted CAR T-cell therapy developed by academia, in patients with relapsed or refractory multiple myeloma. https://pubmed.ncbi.nlm.nih.gov/37414060/ ALSO AS VIDEO ON https://youtu.be/Ymgg22roWGU CONNECT WITH US https://twitter.com/TheEBMT_Trainee https://www.ebmt.org/trainee-committee https://twitter.com/CarmeloGurnari
Immunotherapy with chimeric antigen receptor (CAR)–expressing T cells that target the disialoganglioside GD2 expressed on tumor cells may be a therapeutic option for patients with high-risk neuroblastoma. In an academic, phase 1–2 clinical trial, the investigators enrolled patients (1 to 25 years of age) with relapsed or refractory, high-risk neuroblastoma in order to test autologous, third-generation GD2-CAR T cells expressing the inducible caspase 9 suicide gene (GD2-CART01). https://www.nejm.org/doi/full/10.1056/NEJMoa2210859 ALSO AS VIDEO ON YOUTUBE
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The presence of TP53 mutations is associated with an unfavorable outcome in patients allografted for acute myeloid leukemia (AML), leading some to question the benefit of an allogeneic stem cell transplantation (allo-SCT) for this patient group, although this has not been studied in a large cohort. Article: https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.34268 ALSO AS AUDIO ON
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Richter transformation (RT) is a paradigmatic evolution of chronic lymphocytic leukemia (CLL) into a very aggressive large B cell lymphoma conferring a dismal prognosis. The mechanisms driving RT remain largely unknown.
Article: https://www.nature.com/articles/s41591-022-01927-8
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Risk stratification and therapeutic decision-making for myelodysplastic syndromes (MDS) are based on the International Prognostic Scoring System–Revised (IPSS-R), which considers hematologic parameters and cytogenetic abnormalities. Somatic gene mutations are not yet used in the risk stratification of patients with MDS. Combining genomic profiling with hematologic and cytogenetic parameters, the IPSS-M improves the risk stratification of patients with MDS and represents a valuable tool for clinical decision-making.
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Schimke immuno-osseous dysplasia (SIOD) is a multisystem disorder that is inherited in an autosomal recessive pattern. It usually manifests first with growth failure. Other features of the disease are generally noted in the ensuing evaluation of the growth failure or develop in the following years.
Article: https://www.nejm.org/doi/10.1056/NEJMoa2117028?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed
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Oncogenic alterations underlying B-cell acute lymphoblastic leukemia (B-ALL) in adults remain incompletely elucidated. To uncover novel oncogenic drivers, Marie and her team performed RNA-seq and whole-genome analyses in a large cohort of unresolved B-ALL. Marie and colleagues identified a novel subtype characterized by a distinct gene expression signature and the unique association of two genomic microdeletions. Article link: https://ashpublications.org/blood/article/doi/10.1182/blood.2021014723/484449/Concurrent-CDX2-cis-deregulation-and-UBTF-ATXN7L3
Hemophagocytic lymphohistiocytosis (HLH; hemophagocytic syndrome) is a rare syndrome of potentially fatal, uncontrolled hyperinflammation. Allogeneic hematopoietic stem cell transplantation is indicated in primary, recurrent or progressive HLH, but information about its outcomes in the adult population is limited.
Rafal works at the Department of Hematology, Transplantation and Internal Medicine, Medical University of Warsaw, Warsaw, Poland. And he is part of YoungEHA.
Progression and persistence of malignancies are influenced by the local tumor microenvironment, and future eradication of currently incurable tumors will, in part, hinge on our understanding of malignant cell biology in the context of their nourishing surroundings. Article: https://www.nature.com/articles/s41590-021-00931-3
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Histopathology is elementary in the diagnostics of patients with MDS, but its high-dimensional data are underused. By elucidating the association of morphologic features with clinical variables and molecular genetics, this study highlights the vast potential of convolutional neural networks in understanding MDS pathology and how genetics is reflected in BM morphology. Article: https://bloodcancerdiscov.aacrjournals.org/content/2/3/238
Clonal hematopoiesis (CH) is an age-related, asymptomatic condition in which leukemia-associated somatic mutations are detected in the blood of individuals without a hematologic malignancy. In the nontransplant setting, CH is uniformly associated with adverse outcomes, including an elevated risk of developing hematologic malignancies and an increased risk of nonhematologic outcomes because of altered inflammatory signaling. Current evidence has thus been insufficient to resolve disagreement about whether to screen older candidate donors for CH, and some transplant centers have begun excluding donors found to have CH on the basis of the assumption that the adverse associations of native CH also apply in the context of transplant. This study performed a comprehensive analysis of samples from donors age 40 years or older to determine the impact of CH on overall recipient outcomes, risk of DCL, and measures of graft alloimmune activity. Article: https://ascopubs.org/doi/full/10.1200/JCO.21.02286
Hurler syndrome, also known as mucopolysaccharidosis Type IH (MPS-IH), Hurler's disease, and formerly gargoylism, is a genetic disorder that results in the buildup of large sugar molecules called glycosaminoglycans (GAGs) in lysosomes. The inability to break down these molecules results in a wide variety of symptoms caused by damage to several different organ systems, including but not limited to the nervous system, skeletal system, eyes, and heart. Allogeneic hematopoietic stem-cell transplantation is the standard of care for Hurler syndrome (mucopolysaccharidosis type I, Hurler variant [MPSIH]). However, this treatment is only partially curative and is associated with complications.
Join our conversation with Francesca Tucci from Pediatric Immunohematology and Bone Marrow Transplantation and the San Raffaele Telethon Institute for Gene Therapy, Milan, Italy (Article: https://www.nejm.org/doi/full/10.1056/NEJMoa2106596).
VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a recently described autoinflammatory syndrome characterized by diffuse inflammatory manifestations, predisposition to hematological malignancy, and an association with a high rate of thrombosis. VEXAS is attributed to somatic mutations in the UBA1 gene in hematopoietic stem and progenitor cells with myeloid restriction in mature forms.
Join our conversation with Emma Groarke from the National Cancer Institute, USA, to understand how it was discovered and more.
Article: https://www.nejm.org/doi/10.1056/NEJMoa2026834?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub++0pubmed
Clinical evolution, genetic landscape and trajectories of clonal hematopoiesis in SAMD9/SAMD9L syndromes. Sahoo SS, et al. Nat Med. 2021 Oct;27(10):1806-1817. doi: 10.1038/s41591-021-01511-6
