Prognosis of Binet stage A chronic lymphocytic leukemia patients: the strength of routine parameters

Abstract

Recent developments in the management of chronic lymphocytic leukemia (CLL) patients have made necessary the availability of dependable prognostic factors. We have developed a prognostic index derived from the multivariate analysis of 339 stage A patients at diagnosis, exhaustively studied for classical and recent predictive markers. Only 4 biologic parameters were found to be independent predictors of progression-free survival (PFS): serum thymidine kinase (sTK), lymphocytosis, ␤2-microglobulin, and CD38 expression. Two groups were distinguishable: cases with no or 1 risk factor (among whom 85% did not progress after 7 years), IntroductionWithin the past decade, treatment options in chronic lymphocytic leukemia (CLL) have moved from being palliative to potentially curative. The clinical staging systems developed by Rai et al 1 and Binet et al 2 define early-, intermediate-, and advanced-disease stages. Nonetheless, as substantial variability in the course of the disease is observed among patients at each stage, particularly stage A, 3 there has been a sustained effort to identify reliable prognostic factors in CLL. However, the identification of high-risk (or low-risk) patients remains challenging.Currently, up to 80% of newly diagnosed patients present with Binet stage A. 4 Among them, identifying patients at high risk of progression and precisely evaluating time to progression are fundamental needs for both patients and physicians. For patients with indolent disease, number of follow-up visits may be reduced. Therefore, clinicians in charge of CLL patients would benefit from a simple prognostic index similar to the International Prognostic Index 5 for aggressive non-Hodgkin lymphomas.We exhaustively studied a cohort of 339 stage A CLL patients at diagnosis and determined both typical and specialized prognostic factors. The multivariate analysis allowed us to propose a prognostic score for an easy, fast, and effective assessment of the risk of progression in Binet stage A patients. Methods PatientsOver a period of 8 years, 339 patients diagnosed with CLL in 3 university hospitals were enrolled in the study. All cases were CD5 ϩ CD23 ϩ and had an RMH-Matutes score Ն 4. Patients were followed up from diagnosis until progression to Binet stage B/C. This study was approved by the institutional review board of Hôpital Avicenne. IGHV gene mutational statusIGHV mutational status was evaluated in genomic DNA as previously described. 6 Data obtained after automated sequencer processing were analyzed using the IMGT 7 database. A sequence was considered unmutated when at least 98% identity to the closest germline VH gene was observed. Cytogenetics/targeted chromosome alterationsThe 4 relevant chromosomal abnormalities-del13q, trisomy12, del11q, and del17p-were investigated by interphasic fluorescence in situ hybridization (FISH) analysis. sTKSerum thymidine kinase (sTK) was investigated using a Profiligen TK-Rea kit (Diasorin). CD38 expression by flow cytometryCD38 expression was measured on fresh cells at diagnosis usi...

Chromosomal aberrations and their prognostic value in a series of 174 untreated patients with Waldenstrom's macroglobulinemia

“…In particular, 6q deletion and trisomy 4 are more frequent in WM, while 13q14 deletion is less frequent in WM (13% in Progression-free survival our series) than in CLL and MM (both ~50%). [14][15][16] Interestingly, trisomy 18, which is reported to be common in MZL (10-28%), was also frequent in our series of WM (15%), and was significantly associated with trisomy 4.…”

“…3 The frequency of 11q22 (ATM) deletions is 7-24% in CLL, and this abnormality is often associated with lymphadenopathy and a poor prognosis. 14,22,26 In our series of WM, 11q deletion was associated with advanced age and hypoalbuminemia but had no impact on clinical outcome.…”

“…Chromosomal abnormalities may help with diagnosis and prognostication, in conjunction with other clinical and biological characteristics. Joris Andrieux, 11 Virginie Eclache, 12 Chrystèle Bilhou-Nabera, 13 Isabelle Luquet, 14 Christine Terre, 15 Laurence Baranger, 16 Francine Mugneret, 17 Jean Chiesa, 18 Marie-Joelle Mozziconacci, 19 Evelyne Callet-Bauchu, 20 Lauren Veronese, 21 Hélène Blons, 22 Roger Owen, 23 …”

Development of a comprehensive prognostic index for patients with chronic lymphocytic leukemia

“…Despite these advantages, the clinical staging systems do not fully reflect the high variability of CLL, nor do they account for known biological characteristics of CLL cells predicting survival and response to therapy. 3,6,7 Recently an impressive array of novel effective therapies has been developed that hold the potential of increasingly individualized treatments if patient risk could be accurately characterized. [8][9][10] Unfortunately, the large number of novel prognostic markers in CLL, limited information on their independent prognostic value, and a lack of understanding of how to interpret discordant markers are still major barriers to integrate these in routine clinical CLL practice.…”

The degree of BCR and NFAT activation predicts clinical outcomes in chronic lymphocytic leukemia

“…CLL affects predominantly elderly people and, based on clinical and biologic annotations, the course of the disease can be classified from indolent to more aggressive subtypes. [1][2][3][4][5] CLL is defined as an expansion of monoclonal, slowly dividing CD5 ϩ / CD20 ϩ B lymphocytes. An important prognosis factor for CLL patients is the mutational status of immunoglobulin (Ig) variable heavy chain genes (IGHV) constituting the IgM B-cell antigen receptor (BCR).…”