Prognostic significance of lymphocyte morphology in patients with advanced chronic lymphocytic leukemia treated with first line therapy of fludarabine + prednisone

Abstract

BACKGROUND AND OBJECTIVES: Chronic lymphocytic leukemia (CLL) is characterized by clinical, immunophenotypic and morphologic heterogeneity. The morphologic pattern of CLL lymphocytes at diagnosis has been associated with likelihood of different prognoses, while its prognostic significance at the time of disease progression is uncertain. DESIGN AND METHODS: In 69 previously untreated patients with advanced CLL the morphology of peripheral blood (PB) lymphocytes was retrospectively analyzed prior to therapy with fludarabine (FD: 25 mg/m(2) x 5 consecutive days every 4 weeks) and prednisone (P: 40 mg/m(2) x 5 consecutive days every 4 weeks). Two groups of patients were identified: the first one characterized by typical CLL morphology (T) and < or =11% of atypical lymphocytes, and the second one characterized by >11% of atypical lymphocytes (A). The second group was further subdivided into a group characterized by prolymphocyte prevalence (Ap) and into a group characterized by mixed cell morphology (Amc), with a prevalence of large-sized lymphocytes and/or small, cleaved lymphocytes and/or lymphoplasmocytoid cells with or without shaped nucleus. RESULTS: Forty-two patients (61%) showed a T morphology and 27 (39%) an A morphology. The latter group included 14 patients with an Ap morphology and 13 with an Amc morphology. Two thirds of patients with A morphology showed an immunophenotypic score of 3-4. No significant differences in the distribution of clinical features prior to therapy were observed within the three morphologic groups (T, Ap, Amc), except for a higher lymphocyte count in the Ap group (p<0.05). The morphologic pattern did not have a significant impact on the response rate or on the duration of response. Patients with A morphology did, nonetheless, have a significantly shorter survival than patients with T morphology (p=0.05). However, in multivariate analysis we failed to demonstrate an independent prognostic effect of the lymphocyte morphology observed prior to therapy, while age (< or =55 vs >55 years) and CLL duration (< or =12 vs >12 months) emerged as significant and independent prognostic factors of survival probability. INTERPRETATION AND CONCLUSIONS: The results of this study indicate that about one third of CLL patients with advanced disease have an atypical morphology and that about two thirds of patients with A morphology also show a low immunophenotypic score. The morphologic pattern at the time of progression does not allow identification of prognostic subgroups of patients with different response rates to first line therapy with FD + P.