The mutational landscape of small lymphocytic lymphoma compared to non-early stage chronic lymphocytic leukemia

Abstract

Small lymphocytic lymphoma (SLL) is considered as the non-leukemic form of presentation of chronic lymphocytic leukemia (CLL). We have compared the features, genomic alterations, and outcome of 890 patients with CLL and SLL. One hundred and thirteen patients presented as SLL and more frequently had unmutated-IGHV, CD38^high, ZAP-70^high, CD49d^high, +12, alterations in genes of NOTCH1, cell cycle, RNA metabolism, and NFkB pathways than CLL. During the follow-up, 46% of SLL patients developed CLL. Time to first treatment (TTFT) was shorter in SLL (10-year: 75% vs 62%; p = .006). Binet stage, SLL, and IGHV were independent predictive factors for TTFT. Transformation to diffuse large B-cell lymphoma was higher (10-year: 12% vs 6%; p = .003), and overall survival was shorter in SLL (10-year: 55% vs 66%; p = .004). When A0 CLL patients were excluded, only CD38 and CD49d expression, +12, and 10-year TTFT remained different between the SLL and CLL patients. In summary, SLL showed only minor clinicobiological differences when compared with CLL in similar clinical stages.

Keywords:

• Small lymphocytic lymphoma
• chronic lymphocytic leukemia
• gene mutations
• prognostic factors
• clinicobiological characteristics

Acknowledgements

We are grateful to Sara Guijarro, Silvia Martín, Cristina Capdevila, Montse Sánchez, Miguel Osuna, and Laura Plà for excellent technical assistance, and Nathalie Villahoz and Carmen Muro for excellent work in the coordination of the CLL Spanish Consortium. We are indebted to the HCB-IDIBAPS Biobank-Tumor Bank and Hematopathology Collection for the sample procurement. We are also very grateful to all patients with CLL who have participated in this study.

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article online at https://doi.org/10.1080/10428194.2017.1397660.

Additional information

Funding

This work was funded by the Spanish Ministry of Science and Innovation (MICINN) through the Instituto de Salud Carlos III (ISCIII) (International Cancer Genome Consortium-Chronic Lymphocytic Leukemia Genome Project and FIS-PMP15), red Temática de Investigación del Cáncer (RITCC) of the ISCIII (RD12/0036/0036 [E. Campo], RD12/0036/0023 [A.L.-G.], RD12/0036/0036 [M. G.-D.], Plan Nacional SAF2015-64885-R, Fondo de investigaciones sanitarias PI16/00420), Fellowship Program of Gilead España (GLD15/00288; E. Campo), and Generalitat de Catalunya Suport Grups de Recerca AGAUR (2014-SGR-795 and 2014-SGR-668). E. Campo is a researcher of the Academia Program of the Institució Catalana de Recerca i Estudis Avançats (ICREA) of the Generalitat de Catalunya. This work has been partially developed at the Centro Esther Koplowitz (CEK), Barcelona, Spain.