CIRCULATING BLOOD B-CELLS IN MULTIPLE-MYELOMA - ANALYSIS AND RELATIONSHIP TO CIRCULATING CLONAL CELLS AND CLINICAL-PARAMETERS IN A COHORT OF PATIENTS ENTERED ON THE EASTERN-COOPERATIVE-ONCOLOGY-GROUP PHASE-IIIE9486 CLINICAL-TRIAL

Recent analyses of circulating blood B cells in myeloma have generated controversy concerning the exact levels of these cells and whether th ey may represent circulating clonal tumor B cells. Previous reports su ggested that CD19(+) B cells are markedly increased in myeloma patient s and that this population shares clonotypic rearrangements with the m alignant plasma cell. We studied the numbers of CD19(+) B cells by flo w cytometry in previously untreated newly diagnosed myeloma patients i n Eastern Cooperative Oncology Group (ECOG) phase III trial E9486. The re were 628 patients who were eligible for the clinical protocol E9486 , but of these 521 were also entered on the companion laboratory study (E9487) and had CD19 data. In comparison with normal controls, the my eloma patients exhibited a marked heterogeneity in the number of circu lating CD19(+) B cells as detected by flow cytometry. Approximately 20 % of patients had significantly increased levels of circulating CD19() B cells. However, the total CD19(+) blood population from myeloma wa s not significantly different from the median of age-matched, normal c ontrols. Analysis of CD19(+) blood cells in relationship to circulatin g clonal cells was done in 13 myeloma patients using a clonotypic, qua ntitative allele-specific oligonucleotide-polymerase chain reaction (P CR) assay. No correlation was found between the numbers of CD19(+) B c ells (range, 5% to 51%) and PCR estimates of the number of clonal cell s in the peripheral blood (range, .009% to 3.6%). Low CD19(+) B-cell l evel (<125 mu L) was associated with clinical stage III (P = .033). A significant relationship exists between higher levels (greater than or equal to 125/mu L) of CD19 cells and longer overall survival (P < .00 01). In addition, high CD19 levels also predicted a clinical response and longer event-free survival. There was a strong inverse association between the level of CD19 values at diagnosis and infections within t he first 2 months of diagnosis. Importantly, the number of deaths rela ted to infections was significantly greater in the low versus high CD1 9 group (P < .0202). Also, CD19 is an independent prognostic factor in addition to plasma cell labeling indices, beta(2)-microglobulin, hemo globin, and plasmablastic morphology. Patients with infections were mo re likely to have low levels of CD19(+) cells. In summary, higher CD19 (+) cell levels are a favorable prognostic sign with no apparent relat ionship to circulating tumor cells. In addition, this analysis strongl y suggests that low peripheral blood levels of CD19(+) cells are an ad verse prognostic sign in myeloma. The CD19(+) cell levels in myeloma p atients is an important parameter in the overall assessment of these p atients. (C) 1997 by The American Society of Hematology.