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Blood, 1 November 2001, Vol. 98, No. 9, pp. 2633-2639
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Clinical significance of CD38 expression in chronic
lymphocytic leukemia
Giovanni Del Poeta,
Luca Maurillo,
Adriano Venditti,
Francesco Buccisano,
Anna Maria Epiceno,
Giovanni Capelli,
Anna Tamburini,
Giovanna Suppo,
Alessandra Battaglia,
Maria Ilaria Del
Principe,
Beatrice Del Moro,
Mario Masi, and
Sergio Amadori
From the Cattedra e Divisione di Ematologia,
Università "Tor Vergata," Ospedale S.Eugenio, and the
Istituto di Igiene, Istituti di Ginecologia, Università Cattolica
"Sacro Cuore," Roma, Italy.
B-cell chronic lymphocytic leukemia (B-CLL) follows heterogeneous
clinical courses, and several biological parameters need to be added to
the current clinical staging systems to predict which patients will
experience an indolent or an aggressive outcome. This study
analyzed CD38 expression by flow cytometry and soluble APO1/Fas
(sAPO1/Fas), Bcl-2 (sBcl-2), and CD23 (sCD23) proteins by
immunoenzymatic methods to evaluate their effect on the clinical course
of 168 unselected B-CLL patients. Intermediate/high risk modified Rai
stages were characterized by a higher CD38+ B-cell number
(P = .0002) and higher sCD23 levels
(P < .0001). Moreover, CD38+ B-cell
percentages were significantly and directly associated both with
 2-microglobulin and sCD23 concentrations
(P < .0001 and P = .002, respectively).
Both a higher tumor burden (lymphadenopathy/splenomegaly) and a
lymphocyte doubling time less than 12 months were significantly associated with higher CD38+ percentages (P <
.0001 and P = .0001, respectively). With regard to
clinical outcome, progression-free survival was significantly longer
(75% versus 37% at 5 years; P = .00006) in patients
with lower CD38+ B-cell percentages. Furthermore, the risk
of partial or no response to fludarabine increased with increasing CD38
expression (P = .003), and a shorter overall survival
(50% versus 92% at 8 years; P < .00001) characterized
patients with more than 30% CD38+ B-cell number. The
predictive value of CD38 expression was maintained among the patients
within the Rai intermediate risk group and was confirmed in
multivariate analysis. Thus, the percentage of CD38+ B
cells appears to be an accurate predictor of clinical outcome and
therefore could be used to indicate when more novel chemotherapeutic approaches are needed.
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