Prognostic importance of the pre-B-cell immunophenotype and other presenting features in B-lineage childhood acute lymphoblastic leukemia: a Pediatric Oncology Group study.
Prognostic importance of the pre-B-cell immunophenotype and other presenting features in B-lineage childhood acute lymphoblastic leukemia: a Pediatric Oncology Group study.
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DOI：
10.1182/blood.v74.4.1252.bloodjournal7441252
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发表时间：
1989-09
期刊：
影响因子：
20.3
通讯作者：
W. Crist;J. Boyett;J. Jackson;T. Vietti;M. Borowitz;A. Chauvenet;N. Winick;A. Ragab;Donald H. Mahoney;D. Head;R. Iyer;H. Wagner;J. Pullen
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文献类型：
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作者：
W. Crist;J. Boyett;J. Jackson;T. Vietti;M. Borowitz;A. Chauvenet;N. Winick;A. Ragab;Donald H. Mahoney;D. Head;R. Iyer;H. Wagner;J. Pullen
我们报告了1981年至1986年对早期b前（n = 685）或b前（n = 222）急性淋巴细胞白血病（ALL）儿童进行的随机临床试验中，b前细胞免疫表型和其他表现特征（包括母细胞核型）的预后意义。年龄大于或等于1岁，小于或等于21岁的完全缓解患者按常规风险标准和免疫表型分层，然后随机接受两种强化化疗方案中的一种继续治疗，指定为S（标准）和SAM（标准加中剂量甲氨蝶呤，每8周1 g/m2）。在两个表型定义的亚组中，达到完全缓解的受试者比例相同，为96%。在中位随访时间为42个月时，4年无事件生存率（+/- SE）的总体概率为63% +/- 2% （b前= 51% +/- 5%，b前= 66% +/- 3%）。b前ALL患儿持续完全缓解时间显著缩短（P = 0.0004）；这种关联包括骨髓和中枢神经系统的缓解（P = 0.0004和P = 0.02）。在一项潜在重要预后因素的单变量Cox回归分析中，b前免疫表型与较差的预后显著相关，其他已知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、倍性和性别的多变量模型中，它保持了其预后优势。在临床过程中，具有b前免疫表型的儿童在任何时候失败的风险是缺乏该特征但具有同等风险状态的患者的1.8倍。应该强调的是，本研究中确定的任何重要特征的预测价值都可能在另一种更有效的治疗方案的背景下降低。然而，我们的主要结论是，在一项当代临床试验中，b前ALL患儿的预后比早期b前ALL患儿差，这对患者分层随机化和设计风险特异性治疗方案具有重要意义。
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.