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Ferrata Storti Foundation
Chronic Lymphocytic Leukemia
Prognostic significance of translocations in the presence of mutated IGHV and of cytogenetic complexity at diagnosis of chronic lymphocytic leukemia
ABSTRACT
Mutations of the IGH variable region in patients with chronic lym- phocytic leukemia are associated with a favorable prognosis, whereas cytogenetic complexity (≥3 unrelated aberrations) and translocations have been associated with an unfavorable prognosis. While mutational status of IGHV is stable, cytogenetic aberrations frequently evolve. However, the relationships of these features as prognosticators at diagnosis are unknown. We examined the CpG-stimulated metaphase cytogenetic features detected within 1 year of diagnosis of chronic lym- phocytic leukemia and correlated these features with outcome and other clinical features including IGHV mutational status. Of 329 untreated patients, 53 (16.1%) had a complex karyotype, and 85 (25.8%) had a translocation. The median time to first treatment (TFT) was 47 months. In univariable analyses, significant risk factors for shorter TFT (P<0.05)
Haematologica 2021 Volume 106(6):1608-1615
Nyla A. Heerema,1 Natarajan Muthusamy,2 Qiuhong Zhao,2 Amy S. Ruppert,2 Heather Breidenbach,1 Leslie A. Andritsos,2 Michael R. Grever,2 Kami J. Maddocks,2 Jennifer Woyach,2 Farrukh Awan,2 Meixiao Long,2 Amber Gordon,2 Caitlin Coombes2 and John C. Byrd2
Department of Pathology, The Ohio State University Wexner Medical Center and 2Department of Hematology, The Ohio State University Wexner Medical Center, Columbus, OH, USA
1
were Rai stage 3-4, b 2
-microglobulin >3.5 mg/L, log-transformed white blood cell count, unmutated IGHV, a complex karyotype, a translocation, and trisomy 8, del(11q) or del(17p) detected by fluorescence in situ hybridization. In multivariable analysis, there was a significant effect modification of IGHV status on the relationship between translocation and TFT (P=0.002). In IGHV-mutated patients, those with a translocation had an over 3.5 times higher risk of starting treatment than those without a translocation (P<0.001); however, among IGHV-unmutated patients, a translocation did not significantly increase the risk of starting treatment (hazard ratio 1.00, P=0.99). The effect of Rai stage 3-4, log-transformed white blood cell count and complex karyotype remained statistically sig- nificant, whereas that of del(17p) did not (P=0.51). In summary, the pres- ence of a translocation in IGHV-mutated patients appeared to negate the improved prognosis of mutated IGHV, but the presence of a translocation
did not have an effect on TFT in high-risk IGHV-unmutated patients.
Introduction
Chronic lymphocytic leukemia (CLL) has a varied clinical course. Some patients have an indolent disease with a lifespan similar to that of their peers without the disease. Other patients have rapid disease progression, require treatment early in the course of the disease, are less responsive to therapy, or exhibit short remission after therapy and have a relatively short overall survival. Factors that have prognos- tic significance include clinical variables such as gender, age and Rai/Binet stage, and biological factors such as IGHV mutational status, ZAP70 status and genetic abnormalities as detected by fluorescence in situ hybridization (FISH). IGHV muta- tional status is a significant and independent prognostic factor that does not change over the course of the disease. Patients with unmutated IGHV have a worse prog- nosis than those with mutated IGHV.1-3
Correspondence:
NYLA A. HEEREMA
Nyla.heerema@osumc.edu
Received: November20,2018. Accepted: May 8, 2020. Pre-published: May 15, 2020.
https://doi.org/10.3324/haematol.2018.212571
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