Trainee Pearls

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://w...

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 As VIDEO on https://youtu.be...

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://...

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-genera...

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....

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   ALSO AS AUDIO ON https://podcasts.apple.com/us/podcast/trainee-pearls/id1596786132 ...

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 I...

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?u...

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 uni...

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...

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  CONNECT with Trainee Committee https://twitt...

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....

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 nonhemato...

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,...

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 i...

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