Crist W, Boyett J, Jackson J, Vietti T, Borowitz M, Chauvenet A, Winick N, Ragab A, Mahoney D, Head D
St Jude Children's Research Hospital, Memphis, Tennessee.
Blood. 1989 Sep;74(4):1252-9.
We report the prognostic significance of the pre-B-cell immunophenotype and other presenting features, including blast cell karyotype, in a randomized clinical trial conducted from 1981 to 1986 for children with early pre-B (n = 685) or pre-B (n = 222) acute lymphoblastic leukemia (ALL). Patients greater than or equal to 1 year and less than or equal to 21 years of age who attained complete remission were stratified by conventional risk criteria and immunophenotype and then randomized to receive continuation therapy with either of two regimens of intensive chemotherapy, designated S (standard) and SAM (standard plus intermediate-dose methotrexate, 1 g/m2 every 8 weeks). The proportions of subjects achieving complete remission in the two phenotypically defined subgroups were identical, 96%. At a median follow-up time of 42 months, the overall probability of 4-year event-free survival (+/- SE) was 63% +/- 2% (pre-B = 51% +/- 5% and early pre-B = 66% +/- 3%). Children with pre-B ALL had significantly shorter durations of continuous complete remission (P = .0004); this association included both bone marrow and CNS remissions (P = .0004 and P = .02, respectively). In a univariate Cox regression analysis of potentially important prognostic factors, the pre-B immunophenotype was significantly related to a poorer outcome, as were other recognized biologic and clinical features (eg, pseudodiploidy, older age, male sex, black race, and a higher WBC). It retained its prognostic strength in a multivariate model based on age, WBC, ploidy, and sex. The risk of failure at any point in the clinical course of a child with the pre-B immunophenotype was 1.8 times as great as that in a patient lacking this feature but otherwise having an equivalent risk status. It should be stressed that the predictive value of any of the significant characteristics identified in this study could diminish in the context of another, more effective treatment program. Nevertheless, our major conclusion, that children with pre-B ALL fare worse than those with early pre-B disease in a contemporary clinical trial has implications for stratified randomization of patients and the design of risk-specific treatment protocols.
我们报告了在1981年至1986年针对早期前B细胞（n = 685）或前B细胞（n = 222）急性淋巴细胞白血病（ALL）患儿进行的一项随机临床试验中，前B细胞免疫表型及其他呈现特征（包括原始细胞核型）的预后意义。年龄大于或等于1岁且小于或等于21岁且达到完全缓解的患者，根据传统风险标准和免疫表型进行分层，然后随机接受两种强化化疗方案之一的继续治疗，这两种方案分别指定为S（标准）和SAM（标准加中剂量甲氨蝶呤，每8周1 g/m²）。两个表型定义亚组中实现完全缓解的受试者比例相同，均为96%。在中位随访时间42个月时，4年无事件生存率（±SE）的总体概率为63%±2%（前B细胞型 = 51%±5%，早期前B细胞型 = 66%±3%）。前B细胞ALL患儿的持续完全缓解时间明显更短（P = 0.0004）；这种关联包括骨髓和中枢神经系统缓解（分别为P = 0.0004和P = 0.02）。在对潜在重要预后因素的单变量Cox回归分析中，前B细胞免疫表型与较差的预后显著相关，其他公认的生物学和临床特征（如假二倍体、年龄较大、男性、黑人种族和较高的白细胞计数）也是如此。在基于年龄、白细胞计数、倍性和性别的多变量模型中，它保留了其预后强度。具有前B细胞免疫表型的儿童在临床病程中任何时候的失败风险是缺乏此特征但其他风险状态相当的患者的1.8倍。应该强调的是，在另一个更有效的治疗方案背景下，本研究中确定的任何显著特征的预测价值可能会降低。然而，我们的主要结论是，在当代临床试验中，前B细胞ALL患儿的预后比早期前B细胞疾病患儿更差，这对患者的分层随机化和风险特异性治疗方案的设计具有启示意义。
