TY - JOUR
T1 - B-cell receptor stereotyped subsets and outcome for patients with chronic lymphocytic leukemia in the HOVON 68 trial
AU - Vojdeman, Fie J.
AU - Pedersen, Lone B.
AU - te Raa, Doreen
AU - Juvonen, Vesa
AU - van Norden, Yvette
AU - Tjønnfjord, Geir E.
AU - Kimby, Eva
AU - Itälä-Remes, Maija
AU - Rosenquist, Richard
AU - Langerak, Anton W.
AU - Evers, Ludo M.
AU - Zenz, Thorsten
AU - HOVON 68 trial group
AU - Walewski, Jan
AU - van Oers, Marinus H. J.
AU - Geisler, Christian H.
AU - Kater, Arnon P.
AU - Niemann, Carsten U.
PY - 2021
Y1 - 2021
N2 - Aim: We here assessed the impact of B-cell receptor stereotypy on progression-free survival (PFS) and overall survival in patients from the HOVON 68 trial. Methods: Based on IGHV mutational analyses from participating centers in Sweden, Norway, Finland, Denmark, Poland, and the Netherlands, B-cell receptor stereotyped subsets were assigned using the ARResT/AssignSubsets software. Analysis for recurrent mutations was performed by next-generation sequencing by a 454-base platform. All other clinical data were extracted from the HOVON database by November 2016. Results: In total, 178 out of 192 patients with sequences available were technically suitable for analysis. Thirty-eight patients (21%) were assigned to one of the 19 major subsets: Subset #2 (n = 12, 6.7%), Subset #8 (n = 7, 3.9%), Subset #6 (n = 6, 3.4%), and Subset #1 (n = 5, 2.8%). Other subsets found were: Subsets #3, #5, #31, and #64B. By November 2016, a PFS event had occurred for 150 patients (84%) and 79 patients (44%) had died. The median follow-up time for patients still alive was 78.9 months. Patients with UM-IGHV belonging to Subset #2 had significantly longer PFS than UM-IGHV 3-21-utilizing non-Subset #2 patients [UM-IGHV Subset #2 median PFS 61.3 months (n = 8) vs. UM-IGHV 3-21 non-Subset #2 median PFS 22.3 months (n = 6), P = 0.01]. Overall, no significant differences in PFS between groups were found for patients with M-IGHV. Conclusion: In the HOVON 68 trial. Subset #2 patients had a good treatment outcome comparable to the outcome for non-high-risk patients with chronic lymphocytic leukemia following fludarabine-cyclophosphamide-rituximab-based treatment.
AB - Aim: We here assessed the impact of B-cell receptor stereotypy on progression-free survival (PFS) and overall survival in patients from the HOVON 68 trial. Methods: Based on IGHV mutational analyses from participating centers in Sweden, Norway, Finland, Denmark, Poland, and the Netherlands, B-cell receptor stereotyped subsets were assigned using the ARResT/AssignSubsets software. Analysis for recurrent mutations was performed by next-generation sequencing by a 454-base platform. All other clinical data were extracted from the HOVON database by November 2016. Results: In total, 178 out of 192 patients with sequences available were technically suitable for analysis. Thirty-eight patients (21%) were assigned to one of the 19 major subsets: Subset #2 (n = 12, 6.7%), Subset #8 (n = 7, 3.9%), Subset #6 (n = 6, 3.4%), and Subset #1 (n = 5, 2.8%). Other subsets found were: Subsets #3, #5, #31, and #64B. By November 2016, a PFS event had occurred for 150 patients (84%) and 79 patients (44%) had died. The median follow-up time for patients still alive was 78.9 months. Patients with UM-IGHV belonging to Subset #2 had significantly longer PFS than UM-IGHV 3-21-utilizing non-Subset #2 patients [UM-IGHV Subset #2 median PFS 61.3 months (n = 8) vs. UM-IGHV 3-21 non-Subset #2 median PFS 22.3 months (n = 6), P = 0.01]. Overall, no significant differences in PFS between groups were found for patients with M-IGHV. Conclusion: In the HOVON 68 trial. Subset #2 patients had a good treatment outcome comparable to the outcome for non-high-risk patients with chronic lymphocytic leukemia following fludarabine-cyclophosphamide-rituximab-based treatment.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85153406007&origin=inward
U2 - https://doi.org/10.20517/jtgg.2021.03
DO - https://doi.org/10.20517/jtgg.2021.03
M3 - Article
SN - 2578-5281
VL - 5
SP - 182
EP - 188
JO - Journal of Translational Genetics and Genomics
JF - Journal of Translational Genetics and Genomics
IS - 2
ER -