Dördelmann M, Reiter A, Borkhardt A, Ludwig W D, Götz N, Viehmann S, Gadner H, Riehm H, Schrappe M
Department of Pediatric Hematology and Oncology, Medical School Hannover, Hannover, Germany. The ALL-BFM Group.
Blood. 1999 Aug 15;94(4):1209-17.
To define prognostic factors in infant acute lymphoblastic leukemia (ALL), the outcome of 106 infants (age </=12 months) during 3 consecutive multicenter trials of the Berlin-Frankfurt-Münster group (ALL-BFM 83, 86, and 90) was retrospectively analyzed according to presenting features and early in vivo response to prednisone. The prednisone response was defined as the cytoreduction (number of blood blasts per microliter at day 8) to a 7-day prednisone prephase and 1 intrathecal dose of methotrexate on day 1. Prednisone good responder (PGR; <1,000 blasts/microL) received conventional therapy and prednisone poor responder (PPR; >/=1,000 blasts/microL) received intensified therapy. Infant ALL was characterized by a high incidence of a white blood cell count greater than 100 x 10(3)/microL (57%), central nervous system leukemia (24%), lack of CD10 expression (59%), 11q23 rearrangement (49%) including the translocation t(4;11) (29%), and a comparatively high proportion of PPR (26%), which were all significantly associated with inferior outcome by univariate analysis. The estimated probability for an event-free survival at 6 years (pEFS) was by far better for PGR compared with PPR, who had a dismal prognosis despite intensified treatment (pEFS, 53% +/- 6% v 15% +/- 7%, P =.0001). Infant PGR, who were less than 6 months of age (n = 40), lacked CD10 expression (n = 43), and/or had an 11q23 rearrangement (n = 17) fared significantly better compared with corresponding PPR, as indicated by a pEFS of 44% +/- 8%, 49% +/- 8%, and 41% +/- 12%, respectively. In multivariate analysis, PPR was the strongest adverse prognostic factor (relative risk, 3.3; 95% confidence interval, 1.9 to 5.8; P <.0001). Infants with PGR, comprising a major subgroup (74%) among infants, might successfully be treated with conventional therapy, whereas PPR require new therapeutic strategies, including early treatment intensification or bone marrow transplantation in first remission.
为了确定婴儿急性淋巴细胞白血病（ALL）的预后因素，我们根据临床表现和早期对泼尼松的体内反应，对柏林-法兰克福-明斯特组连续3项多中心试验（ALL-BFM 83、86和90）中的106例婴儿（年龄≤12个月）的预后进行了回顾性分析。泼尼松反应定义为在第8天的细胞减少（每微升血液中的原始细胞数）至7天泼尼松前期和第1天1次鞘内注射甲氨蝶呤后的结果。泼尼松反应良好者（PGR；＜1000个原始细胞/微升）接受常规治疗，泼尼松反应不佳者（PPR；≥1000个原始细胞/微升）接受强化治疗。婴儿ALL的特征是白细胞计数大于100×10³/微升的发生率高（57%）、中枢神经系统白血病（24%）、缺乏CD10表达（59%）、11q23重排（49%）包括易位t(4;11)（29%）以及PPR的比例相对较高（26%），单因素分析显示这些均与较差的预后显著相关。与PPR相比，PGR的6年无事件生存率（pEFS）估计概率要好得多，尽管接受了强化治疗，但PPR的预后仍然很差（pEFS，53%±6%对15%±7%，P = 0.0001）。年龄小于6个月（n = 40）、缺乏CD10表达（n = 43）和/或有11q23重排（n = 17）的婴儿PGR与相应的PPR相比，预后明显更好，pEFS分别为44%±8%、49%±8%和41%±12%。多因素分析显示，PPR是最强的不良预后因素（相对风险，3.3；95%置信区间，1.9至5.8；P＜0.0001）。婴儿PGR占婴儿中的主要亚组（74%），可能通过常规治疗成功治愈，而PPR则需要新的治疗策略，包括早期强化治疗或首次缓解时的骨髓移植。
