Low expression of the myeloid differentiation antigen CD65s, a feature of poorly differentiated AML in older adults: study of 711 patients enrolled in ECOG trials

Abstract

CD65s appears when the progenitor antigen CD34 disappears, suggesting that this sialylated carbohydrate antigen marks a turning point in normal myeloid differentiation. We characterized acute myeloid leukemia (AML) with low CD65s expression (CD65s low AML) in 711 patients entered on seven Eastern Cooperative Oncology Group AML treatment trials (1986)(1987)(1988)(1989)(1990)(1991)(1992)(1993)(1994)(1995)(1996)(1997)(1998)(1999). Of those, 198 (28%) qualified as having CD65s low AML. Morphologically, CD65s low AML was more common in FAB subgroups with minimal differentiation, M0/M1 (P ¼ o0.0001). Early precursor antigens CD34, CD117 and terminal transferase were more frequent in CD65s low than CD65s high AML (P ¼ o0.0001). Myeloperoxidase was present in fewer CD65s low myeloblasts, and the more mature myeloid antigens, CD15 and CD11b, were rarely detected (P ¼ o0.0001). Yet, the two diagnoses did not differ in the distribution of cytogenetic prognostic groups or the occurrence of the multidrug-resistance mediator, P-glycoprotein. CD65s low AML patients were significantly older than CD65s high cases (Po0.0001). Furthermore, the incidence of CD65s low cases increased with age, from 20% in patients under the age of 50 years to 67% in patients older than 80 years (Po0.0001). Overall, complete remission (CR) rate and overall survival were comparable in CD65s low and CD65s high AML. However, among patients 455 years of age, CD65s low AML had a decreased CR rate of 33 vs 44% in CD65s high AML (P ¼ 0.055). Thus, CD65s low AML represents immunophenotypically undifferentiated disease and occurs predominantly in older adults. Although not statistically significant, the observed association between low CD65s expression and decreased CR rate only in patients over the age of 55 is intriguing.

Treatment of myelodysplastic syndrome patients with erythropoietin with or without granulocyte colony-stimulating factor: results of a prospective randomized phase 3 trial by the Eastern Cooperative Oncology Group (E1996)

“…The relatively good prognosis and responsiveness to lenalidomide therapy of del(5q) MDS patients 49 are in agreement with the superior outcome of differentiated, CD65 ϩ AML. 30 Accumulating data in MDS indicate that fatigue and transfusion dependence negatively impact patients' QOL. 12,17,50 In our study, we demonstrated no differences in fatigue and QOL subscale scores between treatment groups (EPO vs SC) at 4 months.…”

“…29 ECOG has used CD65s expression to differentiate between undifferentiated (Յ 30% CD65 ϩ myeloblasts) from differentiated AML (Ͼ 30% CD65 ϩ myeloblasts). 30 …”

Acute myeloid leukaemia in the elderly: a review

“…Multivariate predictors for disease resistance include cytogenetics, beta-2 microglobulin and PS (Albitar et al, 2007;Estey, 2008), and for OS include cytogenetics, age, luekocytosis, LDH, CD34-expression and NPM1 status (Rollig et al, 2010). More blasts at diagnosis predicted worse outcomes (Baudard et al, 1994), as did CD34-positive disease (Rollig et al, 2010), the presence of chromosomal monosomies (Breems et al, 2008;Medeiros et al, 2010), decreased expression of CD65s (Paietta et al, 2003) and increased expression of CD7 (Stasi et al, 1996). Interestingly, age is not a multivariate predictor of outcomes in several models (Chen et al, 2005;Gupta et al, 2005a;Malfuson et al, 2008), suggesting other risk factors may be more important for treatment decisions.…”

CD25 expression status improves prognostic risk classification in AML independent of established biomarkers: ECOG phase 3 trial, E1900

“…The presence of a distinct CD25 POS myeloblast population (range, 19%-99%) defined CD25 positivity (CD25 POS ). Undifferentiated, CD65 (s) LOW , 30 and CD11b POS AML were characterized as previously reported. 31 …”