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: Peter Dreger, Andrea Schnaiter, Thorsten Zenz, Sebastian Böttcher, Marianna Rossi, Peter Paschka, Andreas Bühler, Sascha Dietrich, Raymonde Busch, Matthias Ritgen, Donald Bunjes, Matthias Zeis, Michael Stadler, Lutz Uharek, Christof Scheid, Ute Hegenbart, Michael Hallek, Michael Kneba, Norbert Schmitz, Hartmut Döhner, Stephan Stilgenbauer
• Journal: Blood (Blood) Vol. 121 Issue 16 Pg. 3284-8 (Apr 18 2013) ISSN: 1528-0020 [Electronic] United States
• PMID: 23435461 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Phosphoproteins
• RNA Splicing Factors
• Receptor, Notch1
• Ribonucleoprotein, U2 Small Nuclear
• SF3B1 protein, human
• TP53 protein, human
• Tumor Suppressor Protein p53

Topics

• Adult
• Aged
• Disease-Free Survival
• Female
• Follow-Up Studies
• Hematopoietic Stem Cell Transplantation (methods)
• Humans
• Leukemia, Lymphocytic, Chronic, B-Cell (genetics, surgery, therapy)
• Male
• Middle Aged
• Mutation
• Phosphoproteins (genetics)
• RNA Splicing Factors
• Receptor, Notch1 (genetics)
• Ribonucleoprotein, U2 Small Nuclear (genetics)
• Transplantation, Homologous (methods)
• Treatment Outcome
• Tumor Suppressor Protein p53 (genetics)