Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia: a Southwest Oncology Group/Eastern Cooperative Oncology Group Study.
Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia: a Southwest Oncology Group/Eastern Cooperative Oncology Group Study.
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DOI：
10.1182/blood.v96.13.4075.h8004075_4075_4083
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发表时间：
2000
期刊：
影响因子：
20.3
通讯作者：
M. Slovak;K. Kopecky;P. Cassileth;D. H. Harrington;Karl S. Theil;Anwar Mohamed;E. Paietta;C. Willma
中科院分区：
文献类型：
--
作者：
M. Slovak;K. Kopecky;P. Cassileth;D. H. Harrington;Karl S. Theil;Anwar Mohamed;E. Paietta;C. Willma
在一项临床试验中，对609例年龄小于56岁的既往未经治疗的AML患者进行了细胞遗传学与完全缓解（CR）率、总生存期（OS）和CR后结局的相关性研究，该试验比较了3种强化缓解后治疗：强化化疗、自体移植（ABMT）或来自匹配亲属供体的异基因骨髓移植（alloBMT）。根据治疗前核型将患者分为有利、中等、不利和未知细胞遗传学风险组。CR率在4组之间差异显著（P <.0001）：有利，84%（95%置信区间[CI]，77%-90%）;中等，76%（CI，71%-81%）;不利，55%（CI，48%-63%）;未知，54%（CI，33%-74%）。OS也有相似的显著异质性（P <0.0001），估计的任何原因死亡的相对危险度为1.50（CI，1.10-2.05），3。与有利组相比，中度、不利和未知风险组分别为33（CI，2.43-4.55）和2.66（CI，1.59-4.45）。在多变量分析中，细胞遗传学风险状态对CR率和OS的影响不能用其他患者或疾病特征来解释。在缓解后患者中，CR后生存率在有利、中等和不利组之间差异显著（P =.0003），治疗效果和细胞遗传学风险状态对生存率的影响之间存在显著的相互作用（P =.017）。细胞遗传学良好的患者在ABMT和alloBMT后的表现明显好于单纯化疗，而细胞遗传学不良的患者在alloBMT后的表现更好。细胞遗传学风险状态是预测AML患者对治疗的反应的重要因素;然而，为了在遗传学定义的AML亚群内加强治疗相关性，需要一个显著更大的白血病细胞遗传学数据库。
The associations of cytogenetics with complete remission (CR) rates, overall survival (OS), and outcomes after CR were studied in 609 previously untreated AML patients younger than 56 years old in a clinical trial comparing 3 intensive postremission therapies: intensive chemotherapy, autologous transplantation (ABMT), or allogeneic bone marrow transplantation (alloBMT) from matched related donors. Patients were categorized into favorable, intermediate, unfavorable, and unknown cytogenetic risk groups based on pretreatment karyotypes. CR rates varied significantly (P <.0001) among the 4 groups: favorable, 84% (95% confidence interval [CI], 77%-90%); intermediate, 76% (CI, 71%-81%); unfavorable, 55% (CI, 48%-63%); and unknown, 54% (CI, 33%-74%). There was similar significant heterogeneity of OS (P <.0001), with the estimated relative risk of death from any cause being 1.50 (CI, 1.10-2.05), 3. 33 (CI, 2.43-4.55), and 2.66 (CI, 1.59-4.45) for the intermediate, unfavorable, and unknown risk groups, respectively, compared with the favorable group. In multivariate analyses, the effects of cytogenetic risk status on CR rate and OS could not be explained by other patient or disease characteristics. Among postremission patients, survival from CR varied significantly among favorable, intermediate, and unfavorable groups (P =.0003), with significant evidence of interaction (P =.017) between the effects of treatment and cytogenetic risk status on survival. Patients with favorable cytogenetics did significantly better following ABMT and alloBMT than with chemotherapy alone, whereas patients with unfavorable cytogenetics did better with alloBMT. Cytogenetic risk status is a significant factor in predicting response of AML patients to therapy; however, to tighten treatment correlates within genetically defined AML subsets, a significantly larger leukemia cytogenetic database is warranted.