T-helper phenotypes in the blood of myeloma patients on ECOG phase III trials E9486/E3A93

Abstract

T-helper blood populations are frequently altered in multiple myeloma (MM). We measured the numbers of naive and activated cell subsets in the blood of a cohort of both previously untreated and treated MM patients. Two- colour flow cytometry to detect total CD4+, CD4+, CD45RA+ (naive) and CD4+, CD45RO+ (activated) subsets was then used to quantify the T-cell subsets in controls and MM patients. Previously treated MM patients either on or off treatment (n = 105) had significantly reduced (P < 0.0001) total CD4 and naive/activated cells than controls. Previously treated MM patients sampled for naive/activated cells while currently off therapy (n = 45) had no difference in the levels of CD4 and naive/activated cells compared to the currently treated patients (n = 60). However, newly diagnosed patients (n = 58) had a significantly reduced total CD4 (P = 0.023) and activated CD4 (P = 0.004), but not naive CD4 subsets, compared to controls. CD19+ cell levels above 125/μl were positively associated with higher T-helper cell levels. There was a strong positive association for better overall survival for patients with >395 CD4 cells/μl (P=0.0001). These data indicate that MM patients at diagnosis have altered T helper subsets, with a selective reduction in activated but not naive cells. Subsequent chemotherapy or the disease process contributes to a further reduction in CD4 cells. Importantly, the association of higher CD19+ cell levels with higher T helper cells indicates that certain myeloma patients can be identified with a more quantitatively intact immune system.