A simplified frailty score predicts survival and can aid treatment-intensity decisions in older patients with DLBCL.

Patients with diffuse large B-cell lymphoma (DLBCL) have a median age of 70 years. Yet, empirical knowledge about the treatment of older patients is limited because they are frequently excluded from clinical trials. We aimed to construct a simplified frailty score and examine survival and treatment-related mortality (TRM) according to frailty status and treatment intensity in an older real-world population with DLBCL. All patients aged ≥70 years diagnosed with DLBCL between 2006 and 2016 in southeastern Norway (N = 784) were included retrospectively and divided into training (n = 522) and validation (n = 262) cohorts. We constructed and validated a frailty score based on geriatric assessment variables and examined survival and TRM according to frailty status and treatment. The frailty score identified 3 frailty groups with distinct survival and TRM, independent of established prognostic factors (2-year overall survival [OS]: fit, 82%; unfit, 47%; frail, 14%; P < .001). For fit patients, full-dose R-CHOP (initial dosage >80%) was associated with better survival than attenuated R-CHOP ([R-miniCHOP]; 2-year OS: 86% vs 70%; P = .012), also in adjusted analyses. For unfit and frail patients, full-dose R-CHOP was not superior to R-miniCHOP, whereas an anthracycline-free regimen was associated with poorer survival in adjusted analyses. A simplified frailty score identified unfit and frail patients with a higher risk for death and TRM, which can aid treatment-intensity decisions in older patients with DLBCL. In this study, fit patients benefited from full-dose R-CHOP, whereas unfit and frail patients had no benefit from full-dose R-CHOP over R-miniCHOP. An online calculator for assessment of the frailty score is available at https://wide.shinyapps.io/app-frailty/.

Therapy-related Myeloid Leukemia With the Translocation t(8;19)(p11;q13) Leading to a KAT6A-LEUTX Fusion Gene.

BACKGROUND/AIM: The chromosome translocation t(8;19)(p11;q13) has been reported in only six acute myeloid leukemia (AML) patients. We here present the genetic and clinical features of the seventh AML case with this aberration. MATERIALS AND METHODS: Cytogenetic and molecular genetic investigations were performed on leukemic bone marrow cells from a patient with therapy-related AML. RESULTS: A t(8;19)(p11;q13) was found leading to an in-frame fusion of exon 16 of the lysine acetyltransferase 6A gene (KAT6A) from 8p11 with exon 2 of the leucine twenty homeobox gene (LEUTX) from 19q13 resulting in expression of the otherwise silent LEUTX gene in the leukemic cells. The KAT6A-LEUTX protein is predicted to act as a histone acetyltransferase at its amino-terminal-KAT6A moiety but as a homeobox transcription factor at the LEUTX-carboxyl-terminal moiety. CONCLUSION: The present case is the second therapy-related AML, and the third AML overall, in which both a t(8;19)(p11;q13) and its molecular result, a KAT6A-LEUTX fusion gene, are described. The t(8;19)(p11;q13)/KAT6A-LEUTX deregulates transcription and induces leukemogenesis.