Page 120 - Haematologica July

Ferrata Storti Foundation
Chronic Lymphocytic Leukemia
Low-count monoclonal B-cell lymphocytosis persists after seven years of follow up and is associated with a poorer outcome
Ignacio Criado,1 Arancha Rodríguez-Caballero,1 M. Laura Gutiérrez,1
Carlos E. Pedreira,2 Miguel Alcoceba,3 Wendy Nieto,1 Cristina Teodosio,1 Paloma Bárcena,1 Alfonso Romero,4 Paulino Fernández-Navarro,5
Marcos González,3 Julia Almeida,1* Alberto Orfao1* and The Primary Health Care Group of Salamanca for the Study of MBL
1Cancer Research Centre (IBMCC, USAL-CSIC), Department of Medicine and Cytometry Service (NUCLEUS), University of Salamanca, IBSAL and CIBERONC, Spain; 2Systems and Computing Department (PESC), COPPE, Federal University of Rio de Janeiro (UFRJ), Brazil; 3Hematology Service, University Hospital of Salamanca, IBMCC, IBSAL, CIBERONC and Department of Nursery and Physiotherapy, University of Salamanca, Spain; 4Centro de Atención Primaria de Salud Miguel Armijo, Salamanca, Sanidad de Castilla y León (SACYL), Spain and 5Centro de Atención Primaria de Salud de Ledesma, Salamanca, Sanidad de Castilla y León (SACYL), Spain
ABSTRACT
Low-count monoclonal B-cell lymphocytosis is defined by the pres- ence of very low numbers of circulating clonal B cells, usually phe- notypically similar to chronic lymphocytic leukemia cells, whose biological and clinical significance remains elusive. Herein, we re-evalu- ated 65/91 low-count monoclonal B-cell lymphocytosis cases (54 chronic lymphocytic leukemia-like and 11 non-chronic lymphocytic leukemia- like) followed-up for a median of seven years, using high-sensitivity flow cytometry and interphase fluorescence in situ hybridization. Overall, the clone size significantly increased in 69% of low-count mon- oclonal B-cell lymphocytosis cases, but only one subject progressed to high-count monoclonal B-cell lymphocytosis. In parallel, the frequency of cytogenetic alterations increased over time (32% vs. 61% of cases, respectively). The absolute number of the major T-cell and natural killer cell populations also increased, but only among chronic lymphocytic leukemia-like cases with increased clone size vs. age- and sex-matched controls. Although progression to chronic lymphocytic leukemia was not observed, the overall survival of low-count monoclonal B-cell lym- phocytosis individuals was significantly reduced vs. non-monoclonal B- cell lymphocytosis controls (P=0.03) plus the general population from the same region (P≤0.001), particularly among females (P=0.01); infec- tion and cancer were the main causes of death in low-count monoclonal B-cell lymphocytosis. In summary, despite the fact that mid-term pro- gression from low-count monoclonal B-cell lymphocytosis to high-count monoclonal B-cell lymphocytosis and chronic lymphocytic leukemia appears to be unlikely, these clones persist at increased numbers, usually carrying more genetic alterations, and might thus be a marker of an impaired immune system indirectly associated with a poorer outcome, particularly among females.
Introduction
Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults in the Western world, typically affecting older patients, particularly males, with a median age at diagnosis of 70 years (y) old.1 It is characterized by the accumulation of mature B cells in peripheral blood (PB), bone marrow (BM) and also secondary lymphoid tissues, with a uniquely aberrant CD19+ CD20+lo CD5+/++ CD23+ sIgM-/+lo phenotype and restricted immunoglobulin (Ig) light chain usage.2,3 Typically, CLL
Haematologica 2018 Volume 103(7):1198-1208
*AO and JA contributed equally to this work.
Correspondence:
orfao@usal.es
Received: November 3, 2017. Accepted: March 15, 2018. Pre-published: March 22, 2018.
doi:10.3324/haematol.2017.183954
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/103/7/1198
©2018 Ferrata Storti Foundation
Material published in Haematologica is covered by copyright. All rights are reserved to the Ferrata Storti Foundation. Use of published material is allowed under the following terms and conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode. Copies of published material are allowed for personal or inter- nal use. Sharing published material for non-commercial pur- poses is subject to the following conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode, sect. 3. Reproducing and sharing published material for com- mercial purposes is not allowed without permission in writing from the publisher.
1198
haematologica | 2018; 103(7)
ARTICLE