title: TP53, SF3B1, and NOTCH1 mutations and outcome of allotransplantation for chronic lymphocytic leukemia: six-year follow-up of the GCLLSG CLL3X trial.
abstract: The purpose of this analysis was to provide 6-year follow-up of the CLL3X trial, which studied reduced-intensity allogeneic hematopoietic stem cell transplantation (HSCT) in patients with poor-risk chronic lymphocytic leukemia (CLL), and to investigate the effect of TP53, SF3B1, and NOTCH1 mutations on HSCT outcome. For 90 allografted patients, 6-year overall survival (OS) was 58% and 6-year event-free survival (EFS) was 38%. TP53, SF3B1, and NOTCH1 mutations were found in 30%, 26%, and 14% of the trial population, respectively. By univariate and multivariate analyses, the mutational status of the TP53, SF3B1, and NOTCH1 genes had no significant effect on OS and EFS. Studies of minimal residual disease confirmed durability of CLL eradication in mutated patients. We conclude that HSCT can provide long-term disease control in patients with poor-risk CLL independent of the presence of TP53, SF3B1, and NOTCH1 mutations. The trial has been registered at the US National Cancer Institute as #EU-20554, NCT00281983.
authors: Department of Medicine V, University of Heidelberg, 69120 Heidelberg, Germany. peter.dreger@med.uni-heidelberg.de
authors: Peter
authors: P
authors: Dreger
authors: Andrea
authors: A
authors: Schnaiter
authors: Thorsten
authors: T
authors: Zenz
authors: Sebastian
authors: S
authors: Böttcher
authors: Marianna
authors: M
authors: Rossi
authors: Peter
authors: P
authors: Paschka
authors: Andreas
authors: A
authors: Bühler
authors: Sascha
authors: S
authors: Dietrich
authors: Raymonde
authors: R
authors: Busch
authors: Matthias
authors: M
authors: Ritgen
authors: Donald
authors: D
authors: Bunjes
authors: Matthias
authors: M
authors: Zeis
authors: Michael
authors: M
authors: Stadler
authors: Lutz
authors: L
authors: Uharek
authors: Christof
authors: C
authors: Scheid
authors: Ute
authors: U
authors: Hegenbart
authors: Michael
authors: M
authors: Hallek
authors: Michael
authors: M
authors: Kneba
authors: Norbert
authors: N
authors: Schmitz
authors: Hartmut
authors: H
authors: Döhner
authors: Stephan
authors: S
authors: Stilgenbauer
mesh_terms: D000328:Adult; D000368:Aged; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000601:surgery / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010750:Phosphoproteins / Q000235:genetics*; D000072260:RNA Splicing Factors; D051881:Receptor, Notch1 / Q000235:genetics*; D017413:Ribonucleoprotein, U2 Small Nuclear / Q000235:genetics*; D014184:Transplantation, Homologous / Q000379:methods; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D010750:Phosphoproteins; D000072260:RNA Splicing Factors; D051881:Receptor, Notch1; D017413:Ribonucleoprotein, U2 Small Nuclear; C112491:SF3B1 protein, human; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53