Outcome of Patients With Central Nervous System Multiple Myeloma (CNS-MM) Treated With CNS-Directed Radiation Therapy.

Background: The prognosis of multiple myeloma involving the central nervous system (CNS-MM) is poor. We report outcomes of CNS-MM treated with CNS-directed radiation therapy (RT).

Methods: We retrospectively reviewed patients with CNS-MM treated with CNS-directed RT from 2015 to 2024.

Human Papilloma Virus Circulating Cell-Free DNA Kinetics in Cervical Cancer Patients Undergoing Definitive Chemoradiation.

Purpose: The human papillomavirus (HPV) is a significant cause of cervical cancer. We hypothesized that detecting viral cell-free HPV DNA (cfDNA) before, during, and after chemoradiation (chemoRT) could provide insights into disease extent, clinical staging, and treatment response.

Experimental Design: Sixty-six patients with locally advanced cervical cancer were enrolled between 2017 and 2023.

Inherited thrombocytopenia associated with mutation of UDP-galactose-4-epimerase (GALE).

Severe thrombocytopenia, characterized by dysplastic megakaryocytes and intracranial bleeding, was diagnosed in six individuals from a consanguineous kindred. Three of the individuals were successfully treated by bone marrow transplant. Whole-exome sequencing and homozygosity mapping of multiple family members, coupled with whole-genome sequencing to reveal shared non-coding variants, revealed one potentially functional variant segregating with thrombocytopenia under a recessive model: GALE p.

Mechanism for survival of homozygous nonsense mutations in the tumor suppressor gene .

is essential for repair of DNA double-strand breaks by homologous recombination, and hence for survival. Complete loss of its function is lethal during early embryonic development. Patients who are compound heterozygous for truncating mutations and missense alleles that retain some DNA repair capacity may survive, albeit with very high risk of early onset breast or ovarian cancer and features of Fanconi anemia.

Bone marrow failure unresponsive to bone marrow transplant is caused by mutations in .

We report 5 individuals in 3 unrelated families with severe thrombocytopenia progressing to trilineage bone marrow failure (BMF). Four of the children received hematopoietic stem cell transplants and all showed poor graft function with persistent severe cytopenias even after repeated transplants with different donors. Exome and targeted sequencing identified mutations in the gene encoding thrombopoietin (): THPO R99W, homozygous in affected children in 2 families, and THPO R157X, homozygous in the affected child in the third family.

FAM111B Mutation Is Associated With Inherited Exocrine Pancreatic Dysfunction.

Objectives: Few genetic causes of exocrine pancreatic dysfunction have been described to date. We identified a family with multiple affected members manifesting exocrine pancreatic dysfunction. Additional associated features included facial rash, sparse hair, hypohidrosis, and swelling of the extremities.

Downregulation of MHC-I expression is prevalent but reversible in Merkel cell carcinoma.

Merkel cell carcinoma (MCC) is an aggressive, polyomavirus-associated skin cancer. Robust cellular immune responses are associated with excellent outcomes in patients with MCC, but these responses are typically absent. We determined the prevalence and reversibility of major histocompatibility complex class I (MHC-I) downregulation in MCC, a potentially reversible immune-evasion mechanism.