Pui C-H, Chessells J M, Camitta B, Baruchel A, Biondi A, Boyett J M, Carroll A, Eden O B, Evans W E, Gadner H, Harbott J, Harms D O, Harrison C J, Harrison P L, Heerema N, Janka-Schaub G, Kamps W, Masera G, Pullen J, Raimondi S C, Richards S, Riehm H, Sallan S, Sather H, Shuster J, Silverman L B, Valsecchi M G, Vilmer E, Zhou Y, Gaynon P S, Schrappe M
St. Jude Chidren's Research Hospital and University of Tennessee, Memphis, 38105, USA.
Leukemia. 2003 Apr;17(4):700-6. doi: 10.1038/sj.leu.2402883.
To assess the clinical heterogeneity among patients with acute lymphoblastic leukemia (ALL) and various 11q23 abnormalities, we analyzed data on 497 infants, children and young adults treated between 1983 and 1995 by 11 cooperative groups and single institutions. The substantial sample size allowed separate analyses according to age younger or older than 12 months for the various cytogenetic subsets. Infants with t(4;11) ALL had an especially dismal prognosis when their disease was characterized by a poor early response to prednisone (P=0.0005 for overall comparison; 5-year event-free survival (EFS), 0 vs 23+/-+/-12% s.e. for those with good response), or age less than 3 months (P=0.0003, 5-year EFS, 5+/-+/-5% vs 23.4+/-+/-4% for those over 3 months). A poor prednisone response also appeared to confer a worse outcome for older children with t(4;11) ALL. Hematopoietic stem cell transplantation failed to improve outcome in either age group. Among patients with t(11;19) ALL, those with a T-lineage immunophenotype, who were all over 1 year of age, had a better outcome than patients over 1 year of age with B-lineage ALL (overall comparison, P=0.065; 5-year EFS, 88+/-+/-13 vs 46+/-14%). In the heterogeneous subgroup with del(11)(q23), National Cancer Institute-Rome risk criteria based on age and leukocyte count had prognostic significance (P=0.04 for overall comparison; 5-year EFS, 64+/-+/-8% (high risk) vs 83+/-+/-6% (standard risk)). This study illustrates the marked clinical heterogeneity among and within subgroups of infants or older children with ALL and specific 11q23 abnormalities, and identifies patients at particularly high risk of failure who may benefit from innovative therapy.
为评估急性淋巴细胞白血病(ALL)合并各种11q23异常患者的临床异质性,我们分析了1983年至1995年间由11个合作组和单一机构治疗的497例婴儿、儿童及青年的数据。如此大的样本量使得我们能够根据不同细胞遗传学亚组,对12个月龄以下或以上的患者进行单独分析。伴有t(4;11) ALL的婴儿若疾病特征为对泼尼松早期反应不佳(总体比较P = 0.0005;5年无事件生存率(EFS),反应良好者为0,反应不佳者为23±12%标准误),或年龄小于3个月(P = 0.0003,5年EFS,小于3个月者为5±5%,大于3个月者为23.4±4%),其预后尤其糟糕。泼尼松反应不佳似乎也会使年龄较大的伴有t(4;11) ALL的儿童预后更差。造血干细胞移植未能改善这两个年龄组的预后。在伴有t(11;19) ALL的患者中,所有年龄超过1岁且具有T系免疫表型的患者,其预后优于年龄超过1岁的伴有B系ALL的患者(总体比较,P = 0.065;5年EFS,分别为88±13%和46±14%)。在伴有del(11)(q23)的异质性亚组中,基于年龄和白细胞计数的美国国立癌症研究所-罗马风险标准具有预后意义(总体比较P = 0.04;5年EFS,高风险组为64±8%,标准风险组为83±6%)。本研究阐明了ALL合并特定11q23异常的婴儿或大龄儿童亚组之间及亚组内部显著的临床异质性,并确定了可能从创新疗法中获益的、预后特别差的高危患者。