Pullarkat Vinod, Slovak Marilyn L, Kopecky Kenneth J, Forman Stephen J, Appelbaum Frederick R
Division of Hematology and Hematopoietic Cell Transplantation, Department of Cytogenetics, City of Hope Comprehensive Cancer Center, 1500 East Duarte Road, Duarte, CA 91010, USA.
Blood. 2008 Mar 1;111(5):2563-72. doi: 10.1182/blood-2007-10-116186. Epub 2007 Dec 21.
We examined the prognostic impact of cytogenetics on the outcome of 200 acute lymphoblastic leukemia (ALL) patients 15 to 65 years of age enrolled in Southwest Oncology Group (SWOG)-9400 study. Evaluable cytogenetics or fluorescence in situ hybridization studies were available in 140 (70%) patients. Four karyotype categories (normal [n = 31, 22%], t(9;22)/BCR/ABL1 [n = 36, 26%], other unfavorable [-7, +8, or 11q23 rearrangement, n = 19, 13%], and miscellaneous [n = 54, 39%]) and the biologically and clinically relevant ALL ploidy subgroups were prospectively defined. Overall survival (OS) decreased significantly with increasing age (P = .009) and varied with karyotype category (P < .001). OS was worst for t(9;22)/BCR/ABL1 followed by other unfavorable karyotypes, with hazard ratios (HR) of 3.45 (95% confidence interval [CI], 1.88-6.31) and 2.14 (95% CI, 1.04-4.04), respectively, compared with normal diploid group. OS of the miscellaneous group was similar to that of the normal diploid group (HR = 0.82; 95% CI, 0.44-1.53). Relapse-free survival (RFS) was not significantly associated with age (P = .30) but was heterogeneous among karyotype categories (P < .001) primarily because of poor RFS in t(9;22)/BCR/ABL1 (HR = 3.49; 95% CI, 1.80-6.75) compared with the normal diploid group. After accounting for the variation among karyotype groups, age was not a significant prognostic factor for OS or RFS, highlighting cytogenetics as the most important prognostic factor in adult ALL. This trial was registered at www.ClinicalTrials.gov as #NCT00002665.
我们研究了细胞遗传学对西南肿瘤协作组(SWOG)-9400研究中纳入的200例15至65岁急性淋巴细胞白血病(ALL)患者预后的影响。140例(70%)患者可进行可评估的细胞遗传学或荧光原位杂交研究。前瞻性定义了四种核型类别(正常[n = 31,22%]、t(9;22)/BCR/ABL1[n = 36,26%]、其他不良核型[-7、+8或11q23重排,n = 19,13%]和其他[n = 54,39%])以及生物学和临床相关的ALL倍体亚组。总生存期(OS)随年龄增加显著降低(P = .009),且因核型类别而异(P < .001)。t(9;22)/BCR/ABL1患者的OS最差,其次是其他不良核型,与正常二倍体组相比,风险比(HR)分别为3.45(95%置信区间[CI],1.88 - 6.31)和2.14(95%CI,1.04 - 4.04)。其他组的OS与正常二倍体组相似(HR = 0.82;95%CI,0.44 - 1.53)。无复发生存期(RFS)与年龄无显著相关性(P = .30),但在核型类别之间存在异质性(P < .001),主要是因为与正常二倍体组相比,t(9;22)/BCR/ABL1患者的RFS较差(HR = 3.49;95%CI,1.80 - 6.75)。在考虑核型组之间的差异后,年龄对OS或RFS不是一个显著的预后因素,这突出了细胞遗传学是成人ALL中最重要的预后因素。该试验在www.ClinicalTrials.gov上注册为#NCT00002665。