Greipp P R, Leong T, Bennett J M, Gaillard J P, Klein B, Stewart J A, Oken M M, Kay N E, Van Ness B, Kyle R A
Mayo Clinic, Rochester, MN 55905, USA.
Blood. 1998 Apr 1;91(7):2501-7.
We studied the prognostic significance of plasmablastic (PB) multiple myeloma (MM) in Eastern Cooperative Oncology Group Phase III trial E9486. Two reviewers independently reviewed 453 cases. They agreed on 37 PB (8.2%) cases and 416 non-PB cases, achieving an 85% concordance (P < .0001). These PB cases had significantly lower hemoglobin and serum albumin levels, higher calcium and beta 2-microglobuin levels, and higher percentage BM plasma cells (PC) by immunofluorescence. They had higher bone marrow PC labeling indices, higher serum soluble interleukin-6 receptor (sIL-6R) levels, and a higher probability of ras mutations. Three treatment regimens were used: vincristine, bis-chloro-ethyl nitrosourea (BCNU) melphalan, cyclophosphamide, and prednisone (VBMCP) alone; VBMCP with added cyclophosphamide (HiCy); or recombinant interferon alpha 2 (rIFNalpha2). Although the numbers are low, patients with PB had a significantly lower response rate versus non-PB MM when treated with VBMCP (treated, 47.1% v nontreated, 66.5% [P = .015]). Patients with nonresponding PB had a significantly higher progression rate than non-PB cases (30.6% v 11.8% [P < .0001]), especially with VBMCP alone (35.3% v 15.8% [P = .002]), and with added HiCy (37.5% v 9.8% [P < .0001]), but not with added rIFNalpha2. Event-free and overall survival of PB MM was shorter (median years, 1.1 v 2.7 and 1.9 v 3.7, respectively [P < .0001 for both]). In multivariate analysis, PB classification was also highly prognostic. There is no survival difference between the patients who were classified as PB by both reviewers versus patients classified as PB by only one reviewer. We conclude that PB MM is a discrete entity associated with more aggressive disease and shortened survival. Tumor cell ras mutations and increased sIL-6R may contribute to a higher proliferation rate and reduced survival. There were significant improvements in response and progression with the addition of HiCy and rIFNalpha2 to VBMCP, but the numbers were small and improved survival could not be shown.
我们在东部肿瘤协作组（Eastern Cooperative Oncology Group）的III期试验E9486中研究了浆母细胞性（PB）多发性骨髓瘤（MM）的预后意义。两名审阅者独立审阅了453例病例。他们对37例PB（8.2%）病例和416例非PB病例达成一致意见，一致性为85%（P <.0001）。这些PB病例的血红蛋白和血清白蛋白水平显著较低，钙和β2-微球蛋白水平较高，免疫荧光检测显示骨髓浆细胞（PC）百分比更高。它们具有更高的骨髓PC标记指数、更高的血清可溶性白细胞介素-6受体（sIL-6R）水平以及更高的ras突变概率。使用了三种治疗方案：单独使用长春新碱、双氯乙基亚硝脲（BCNU）、美法仑、环磷酰胺和泼尼松（VBMCP）；添加环磷酰胺的VBMCP（HiCy）；或重组干扰素α2（rIFNα2）。尽管病例数较少，但与非PB MM患者相比，PB患者接受VBMCP治疗时的缓解率显著较低（治疗组为47.1%，未治疗组为66.5% [P = 0.015]）。无反应的PB患者的进展率显著高于非PB病例（30.6%对11.8% [P <.0001]），尤其是单独使用VBMCP时（35.3%对15.8% [P = 0.002]）以及添加HiCy时（37.5%对9.8% [P <.0001]），但添加rIFNα2时并非如此。PB MM的无事件生存期和总生存期较短（中位年数分别为1.1对2.7和1.9对3.7 [两者P均<.0001]）。在多变量分析中，PB分类也具有高度预后价值。两位审阅者均将其分类为PB的患者与仅一位审阅者将其分类为PB的患者之间的生存期无差异。我们得出结论，PB MM是一种与更具侵袭性的疾病和生存期缩短相关的离散实体。肿瘤细胞ras突变和sIL-6R增加可能导致更高的增殖率和生存期缩短。在VBMCP中添加HiCy和rIFNα2后，缓解和进展情况有显著改善，但病例数较少，未能显示出生存期的改善。
