Kay N E, Leong T, Kyle R A, Greipp P, Billadeau D, Van Ness B, Bone N, Oken M M
Department of Medicine, University of Kentucky Medical Center, Lexington 40536-0093, USA.
Blood. 1997 Jul 1;90(1):340-5.
Recent analyses of circulating blood B cells in myeloma have generated controversy concerning the exact levels of these cells and whether they may represent circulating clonal tumor B cells. Previous reports suggested that CD19+ B cells are markedly increased in myeloma patients and that this population shares clonotypic rearrangements with the malignant plasma cell. We studied the numbers of CD19+ B cells by flow cytometry in previously untreated newly diagnosed myeloma patients in Eastern Cooperative Oncology Group (ECOG) phase III trial E9486. There 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 myeloma patients exhibited a marked heterogeneity in the number of circulating 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 was not significantly different from the median of age-matched, normal controls. Analysis of CD19+ blood cells in relationship to circulating clonal cells was done in 13 myeloma patients using a clonotypic, quantitative allele-specific oligonucleotide-polymerase chain reaction (PCR) assay. No correlation was found between the numbers of CD19+ B cells (range, 5% to 51%) and PCR estimates of the number of clonal cells in the peripheral blood (range, .009% to 3.6%). Low CD19+ B-cell level (<125 microL) was associated with clinical stage III (P = .033). A significant relationship exists between higher levels (> or = 125/microL) of CD19 cells and longer overall survival (P < .0001). 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 the first 2 months of diagnosis. Importantly, the number of deaths related to infections was significantly greater in the low versus high CD19 group (P < .0202). Also, CD19 is an independent prognostic factor in addition to plasma cell labeling indices, beta2-microglobulin, hemoglobin, and plasmablastic morphology. Patients with infections were more likely to have low levels of CD19+ cells. In summary, higher CD19+ cell levels are a favorable prognostic sign with no apparent relationship to circulating tumor cells. In addition, this analysis strongly suggests that low peripheral blood levels of CD19+ cells are an adverse prognostic sign in myeloma. The CD19+ cell levels in myeloma patients is an important parameter in the overall assessment of these patients.
最近对骨髓瘤患者循环血液B细胞的分析引发了关于这些细胞的确切水平以及它们是否可能代表循环克隆性肿瘤B细胞的争议。先前的报告表明，骨髓瘤患者中CD19⁺ B细胞明显增多，且这一群体与恶性浆细胞具有克隆型重排。我们通过流式细胞术研究了东部肿瘤协作组（ECOG）III期试验E9486中未经治疗的新诊断骨髓瘤患者的CD19⁺ B细胞数量。有628例患者符合临床方案E9486的条件，但其中521例也参与了配套的实验室研究（E9487）并拥有CD19数据。与正常对照组相比，通过流式细胞术检测发现，骨髓瘤患者循环CD19⁺ B细胞数量存在明显异质性。约20%的患者循环CD19⁺ B细胞水平显著升高。然而，骨髓瘤患者血液中总的CD19⁺细胞群体与年龄匹配的正常对照组中位数无显著差异。使用克隆型定量等位基因特异性寡核苷酸聚合酶链反应（PCR）分析，对13例骨髓瘤患者的CD19⁺血细胞与循环克隆细胞的关系进行了研究。未发现CD19⁺ B细胞数量（范围为5%至51%）与外周血中克隆细胞数量的PCR估计值（范围为0.009%至3.6%）之间存在相关性。低CD19⁺ B细胞水平（<125 μL）与临床III期相关（P = 0.033）。CD19细胞水平较高（≥125/μL）与总生存期较长显著相关（P < 0.0001）。此外，高CD19水平还预示着临床缓解和较长的无事件生存期。诊断时CD19值水平与诊断后前2个月内的感染之间存在强烈的负相关。重要的是，低CD19组与高CD19组相比，与感染相关的死亡人数显著更多（P < 0.0202）。此外，除了浆细胞标记指数、β2微球蛋白、血红蛋白和浆母细胞形态外，CD19还是一个独立的预后因素。感染患者更可能具有低水平的CD19⁺细胞。总之，较高的CD19⁺细胞水平是一个良好的预后标志，与循环肿瘤细胞无明显关系。此外，该分析强烈表明，骨髓瘤患者外周血中低水平的CD19⁺细胞是不良预后标志。骨髓瘤患者的CD19⁺细胞水平是这些患者总体评估中的一个重要参数。
