CLINICAL RELEVANCE OF P-GLYCOPROTEIN EXPRESSION IN DE-NOVO ACUTE MYELOID-LEUKEMIA

Cytofluorimetric detection of the multidrug resistance (MDR)-associate d membrane protein (P-170) was performed at the time of diagnosis in 1 58 patients with acute myeloid leukemia using the C219 monoclonal anti body (MoAb). In 108 of these cases the JSB1 MoAb was also tested. An i mproved histogram subtraction analysis, based on curve fitting and a s tatistical test was applied to distinguish antigen-positive from antig en-negative cells. A marker was considered positive when more than 20% of the cells were stained. At onset, P-170 was detected in 43% of cas es with C219 and in 73% of cases with JSB1. There was a strict correla tion between C219 and JSB1 positivity, as all C219(+) cases were also positive for JSB1 MoAb (P<.001). No relationship was found between sex , age, organomegaly, and MDR phenotype. Significant correlation was fo und between CD7 and both C219 and JSB1 expression (P<.001 and .001, re spectively). C219-negative phonotype was more often associated with a normal karyotype (24 of 55 with P=.030). Rhodamine 123 (Rh123) stainin g and flow cytometry analysis showed a significantly decreased mean fl uorescence in 51 C219(+) and 38 JSB1(+) patients compared to 42 MDR ne gative ones (P<.001). The rate of first complete remission (OR) differ ed both between 0219(+) and C219(-) cases and between JSB1(+) and JSB1 (-) ones (30.9% v 71.1% and 35.4% v 93.1%, respectively, P<.001). Of t he 21 C219(+) patients who had yielded a first OR, 19 (90.4%) relapsed , compared with 28 of 64 (43.7%) C219(-) patients (P<.001). Of the 28 JSB1(+) patients in first CR, 17 (60.7%) relapsed relative to 8 (29.6% ) of 27 JSB1(-) ones (P=.021). A higher rate of relapses among MDR(+) compared with MDR(-) patients was observed both for C219 and JSB1 MoAb s taken separately (C219 80% v 44%; JSB1 52% v 27%), with no relations hip to age. The survival rates (Kaplan-Meyer method) were significantl y shorter both in C219(+) patients and in JSB1(+) cases (P<.001). Dise ase-free survival curves followed this same trend. The combination (C2 19(-) JSB1(+)) identified a subset of patients with an intermediate ou tcome compared to C219 positive cases. The prognostic value of both ma rkers (C219 and JSB1) was confirmed in multivariate analysis. These re sults suggest that the assessment of MDR phenotype by flow cytometry m ay be an important predictor of treatment outcome. (C) 1996 by The Ame rican Society of Hematology.