Extramedullary Infiltrates of AML: Biological and Clinical Features in a Single Centre Experience.

Abstract

Extramedullary infiltration (EMI) of malignant myeloid precursor cells in acute myeloid leukemia (AML) may occasionally be a presenting clinical symptom at onset and may develop at any site in the body but most commonly in the gum, skin, central nervous system (CNS) and soft tissue. There is controversy about the prognostic significance of extramedullary disease in AML. The present study examines the incidence, the biological features and prognostic significance of EMI at diagnosis in adult patients with AML. From January 1997 to December 2004, 213 untreated patients with de novo AML were studied. According to Grimwade et al, 14 patients were in the favorable-risk group, 159 in the intermediate-risk group, 25 in the poor risk group and in 15 the karyotype was not available. All patients had been treated with induction therapy according to the GIMEMA protocols including cytarabine, etoposide and idarubicin (15 pts), or mitoxantrone (15 pts) or daunorubicin (183 pts).Of 213 cases with de novo AML, 29 (14%) had EMI at diagnosis. Ten patients (34.8%) had skin infiltrates, 12 (41.4%) had gum hypertrophy, 5 (17.2%) had CNS involvement and 2 (6.9%) had soft tissue infiltration. No significant differences in terms of sex, age median Hb level and platelets count were found between patients with EMI and patients without EMI. The patients with EMI had higher median WBC counts (27 × 109/L) than patients without EMI (8.5 × 109/L) (p=0.05). The patients with EMI had a higher incidence of the M4/M5 FAB subtype (62%) than patients without EMI (27.4%) (p=0.005). Cytogenetic analysis was performed in patients with and without EMI; none of the abnormal cytogenetic findings was associated with EMI. We evaluated the relationship between the AML blasts surface antigen expression and EMI; the association between CD56/CD4 and CD56/CD14 was more significantly expressed in patients with EMI (35% and 29%, respectively) than without EMI (10.4% and 6.9%, respectively) (p=0.004, p=0.003).The overall CR rate was 65%; the CR rate was lower in patients with EMI (48.2%) than patients without EMI (76.1%) (p=0.001) and their disease free survival was also shorter (p=0.017); the median duration of CR was 10 and 25 months (range 2–96) in EMI and no EMI group, respectively.Our data show that a high WBC count, M4/M5 subtype, CD56/CD4 and CD56/CD14 expression are associated with extramedullary infiltrates of AML at diagnosis; the presence of EMI adversely affects the complete response rate to induction chemotherapy and the OS rate. Analysis of the clinical and biologic features in a larger series of adult AML patients is needed to evaluate the allocation of this subgroup in a different or more intensive treatment arm.