Differentiating chronic lymphocytic leukemia from monoclonal B-lymphocytosis according to the clinical outcome: on behalf of the GIMEMA Chronic Lymphoproliferative Diseases Working Group

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BlankHaematologica 2010, 10.3324/haematol.2010.030189

Differentiating chronic lymphocytic leukemia from monoclonal B-lymphocytosis

according to the clinical outcome: on behalf of the GIMEMA Chronic

Lymphoproliferative Diseases Working Group

Stefano Molica1,*, Francesca Mauro2, relli3, Francesco Lauria4,

Agostino Cortelezzi5, Maura Brugiatelli6, Vincenzo Liso7, Cuneo8, Robin

Foa'2

1 Dept Hematology-Oncology, Azienda Ospedaliera Pugliese-Ciaccio, Catanzaro,

Italy;

2 Dept. of Cellular Biotechnologies and Hematology, Div. of Hematology, Sapienza

Univ., Rome, Italy;

3 Biostatistics, Regina Elena National Cancer Institute, Rome, Italy;

4 Department of Hematology and Transplant, University of Siena, AOUS, Siena,

Italy;

5 Fondazione Ospedale Maggiore Policlinico, Mangiagalli, Milano, Italy;

6 Department of Hematology, Azienda Ospedaliera Papardo, Messina, Italy;

7 Hematology Section, DAP, University of Bari, Italy;

8 Hematology Section, St. University Hospital, University of Ferrara, Italy

* Corresponding author; email: smolica@...

ABSTRACT

Background. Optimal lymphocyte parameters and thresholds for the diagnosis of

chronic lymphocytic leukemia have been proposed by The National Cancer

Institute-sponsored Working Group and recently updated by the International

Workshop on chronic lymphocytic leukemia. However, it is not clear how these

criteria apply to the management of patients in the daily clinical practice and

whether the lymphocyte thresholds recommended truly predict for clinical outcome

in early chronic lymphocytic leukemia.

Design and Methods. An observational database of the GIMEMA (Gruppo Italiano

Malattie EMatologiche dell' Adulto), which included 1158 patients with newly

diagnosed Binet stage A chronic lymphocytic leukemiawho were observed at

different primary hematology centers during the period 1991-2000, was used for

the purpose of this study.

Results. Among 818 consecutive chronic lymphocytic leukemia patients with Rai

stage 0 (i.e., no palpable lymphadenopathy or hepatosplenomegaly) who had flow

cytometry evaluations at the time of diagnosis and were included in a GIMEMA

database, both absolute lymphocyte count and B-cell count had a similar value in

predicting time to first treatment as continuous variables (P<0.0001). Receiver

operating characteristic analysis identified an absolute lymphocyte count of

11.5x109/L and an absolute B-cell count of 10.0x109/L as the best thresholds

capable of separating patients who will require treatment from those with stable

disease. However, in a multivariate analysis only the B-cell count retained

its discriminating power (P<0.0001) and the estimated rate of progression to

chronic lymphocytic leukemia requiring treatment among subjects with a B-cell

count <10.0x109/L was approximately 2.3% per year (95% CI, 2.1-2.5%) while it

was two-fold higher for patients with a B-cell count of =/>10.0x109/L (i.e.,

5.2% per year; 95% CI=4.9-5.5%). Finally, in this community-based patient cohort

the B-cell threshold defined by investigators at the Mayo Clinic (i.e.,

11.0x109/L) allowed to separate patients into two subsets with a higher and

lower likelihood of treatment (P<0.0001).

Conclusions. Our results, based on a retrospective patients' cohort, provide a

clear justification to retain the B-cell count as the reference gold standard of

chronic lymphocytic leukemia diagnosis and imply that a count of 10x109/L B

cells is the best lymphocyte threshold to predict time to first treatment. The

use of clinical outcome to distinguish chronic lymphocytic leukemia from other

premalignant conditions, such as monoclonal B-cell lymphocytosis, is a pragmatic

approach meeting the patients' need to minimize the psychological discomfort of

receiving a diagnosis of leukemia when the risk of adverse clinical

consequencesis low.