Prognostic Scoring System in CLL

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[2328] Definition of a Prognostic Scoring System for Predicting

Clinical Outcome in B-Cell Chronic Lymphocytic Leukemia. Session

Type: Poster Session, Board #506-II

Fortunato Morabito, Giovanna Cutrona, Massimo Gentile, Serena Matis,

Colombo, Eugenio Lucia, Mauro Spriano, Edoardo Rossi, Vincenzo

Callea, Caterina Stelitano, Carla Mazzone, Ernesto Vigna, Carlo

Gentile, Gianluca Festini, Antonino Neri, Simonetta Zupo, Stefano

Molica, Chiorazzi, Manlio Ferrarini Hematology, Azienda Osp.

di Cosenza, Cosenza, Italy; Medical Oncology C, Istituto Nazionale

per la Ricerca sul Cancro, Genova, Italy; Hematology, Azienda Osp. S.

o, Genova, Italy; Hematology, Azienda Osp. Bianchi-Melacrino-

Morelli, Reggio Calabria, Italy; Hematology, Ospedale Maggiore

Trieste, Trieste, Italy; Hematology 2, Ospedale Maggiore IRCCS,

Milano, Italy; Diagnostica Mal. Linfoprol, Istituto Nazionale per la

Ricerca sul Cancro, Genova, Italy; Hematology/Oncology, Azienda Osp.

Pugliese-Ciaccio, Catanzaro, Italy; The Feinstein Institute for

Medical Research, North Shore University Hospital, Manhasset, NY, USA

Patients whose cells utilize unmutated Ig VH region genes and/or

express ZAP-70 or CD38 have a more aggressive course than patients

whose cells have mutated Ig VH genes and/or do not express ZAP-70 or

CD38.

We have conducted here a study on 500 patients characterized for

marker expression. By ROC curve analysis, we found 30% as the best

cut-off value of CD38 which discriminates between mutated and

unmutated cases in CLLs. CD38 expression, had low sensitivity (66%),

but relatively high specificity (80%), with a positive and a negative

predictive value respectively of 68% and 78% in anticipating VH

mutational status. Moreover, the agreement between CD38 expression

and VH mutational status was low although significant (K=0.46,

p<0.001). ZAP-70 showed high sensitivity (76%) and specificity (75%),

high negative (89%) but a low positive (54%) predictive value and a

low, although significant, K statistic (0.45, p<0.001).

Furthermore, we combined CD38 and Zap-70 expression to evaluate

whether both variables provided more precise information in

estimating VH mutational status.

We found sensitivity, 42%; specificity, 97%; positive predictive

value, 90%; negative predictive value, 72%; K statistic 0.43,

p<0.001.

In conclusion neither CD38 nor ZAP-70 by themselves or in combination

were able to anticipate VH mutational status, meaning that CD38

and/or Zap-70 expression could surrogate the VH mutational status. In

the second part of this study we wanted to validate this findings on

clinical ground.

Clinical information was available for 150/500 CLL cases

investigated. After a median follow-up of 38 months, 83 cases

remained untreated, while 67 cases received treatment. We show that

these markers predict the clinical course by using time to first

treatment (TTT) as a measure for disease progression.

Each of the three markers was capable of discriminating two distinct

groups of patients (p<0.0001 for CD38, p<0.00001 for ZAP-70 and Ig VH

mutations) with different clinical behavior, although marker

combinations provided a more precise definition of prognosis.

Although many patients expressed all favorable or all unfavorable

markers, there also were patients with different marker combinations.

We devised a scoring system that subdivides patients based on the

absence (score 0) or presence of 1 (score 1), 2 (score 2), or 3

(score 3) unfavorable prognostic markers. Using this scoring system,

we have identified 3 groups with significantly different clinical

courses: i.e., low- (score 0), intermediate-risk (score 1) and high-

risk (score2-3) patients. This scoring system has potential

utilization for prognostic stratification of CLL in designing

prospective clinical trials.