Slovak M L, Kopecky K J, Wolman S R, Henslee-Downey J P, Appelbaum F R, Forman S J, Blume K G
Department of Cytogenetics, City of Hope National Medical Center, Duarte, CA, USA.
Leuk Res. 1995 Jun;19(6):381-8. doi: 10.1016/0145-2126(94)00162-4.
A retrospective cytogenetic study was performed to determine whether non-random chromosome aberrations were related to the outcome of marrow transplantation for advanced stage acute leukemia (AL) and chronic myelogenous leukemia (CML). The patients were registered on SWOG-8612, a randomized comparison of busulphan and cyclophosphamide (BU/CY) to fractionated total body irradiation and etoposide (FTBI/VP16) as preparatory regimens for allogeneic bone marrow transplant (BMT). Blume K. G., Kopecky K. J., Henslee-Downey J. P., Forman S. J., Stiff P. J., Le Maistre C. F. & Appelbaum F. R. (1987) Blood 81, 2187. Pretreatment cytogenetic studies were available for 90 (78%) of the 115 patients who proceeded to BMT. Patients were categorized by diagnosis (ALL/AML/CML), disease status ['good' risk = second complete remission (CR2) or CML-accelerated phase (AP); 'poor' risk = third complete remission (CR3), induction failure, florid relapse or CML-blast phase (BP)] and cytogenetic status (favorable = normal cytogenetics in AL or Philadelphia chromosome positive (Ph+) standard or variant translocation as the sole findings in CML; unfavorable = all other cytogenetic aberrations). Chromosomal aberrations observed in the unfavorable category included -7, t(9;22) in AL, t(8;21) in association with complex karyotypes, t(6;9), del(9q), t/del(11q), t(1;19), hypotetraploidy, and complex karyotypes (> 3 cytogenetic anomalies). Unfavorable cytogenetic status was significantly more frequent among patients with 'poor' risk clinical disease status (P < 0.0001). In multivariate analysis, disease-free survival (DFS) was significantly poorer for patients with unfavorable cytogenetic status (P = 0.002) but not significantly related to disease status (P = 0.43). These data indicate that certain secondary chromosome aberrations [+8,i(17q), duplication of Ph] should be reclassified as relatively favorable predictors of successful BMT in CML and, therefore, be separated from the unfavorable cytogenetic aberrations characteristic of drug resistant disease [-7, inv(3), complex karyotypes]. The limited number of patients precluded definitive assessment of the prognostic significance of specific cytogenetic aberrations for any single diagnosis. Nevertheless, these findings suggest that cytogenetic status may be an important and independent factor in predicting outcome following allogeneic bone marrow transplantation.
进行了一项回顾性细胞遗传学研究，以确定非随机染色体畸变是否与晚期急性白血病（AL）和慢性粒细胞白血病（CML）的骨髓移植结果相关。患者登记在SWOG - 8612研究中，该研究将白消安和环磷酰胺（BU/CY）与分次全身照射和依托泊苷（FTBI/VP16）作为异基因骨髓移植（BMT）的预处理方案进行了随机比较。Blume K.G., Kopecky K.J., Henslee - Downey J.P., Forman S.J., Stiff P.J., Le Maistre C.F. & Appelbaum F.R.（1987年），《血液》81卷，2187页。在进行BMT的115名患者中，90名（78%）有预处理细胞遗传学研究数据。患者按诊断（ALL/AML/CML）、疾病状态[“良好”风险 = 第二次完全缓解（CR2）或CML加速期（AP）；“不良”风险 = 第三次完全缓解（CR3）、诱导失败、明显复发或CML急变期（BP）]和细胞遗传学状态（有利 = AL中细胞遗传学正常或CML中仅发现费城染色体阳性（Ph +）标准或变异易位；不利 = 所有其他细胞遗传学畸变）进行分类。在不利类别中观察到的染色体畸变包括 - 7、AL中的t(9;22)、与复杂核型相关的t(8;21)、t(6;9)、del(9q)、t/del(11q)、t(1;19)、亚四倍体和复杂核型（> 3种细胞遗传学异常）。在“不良”风险临床疾病状态的患者中，不利细胞遗传学状态明显更常见（P < 0.0001）。在多变量分析中，细胞遗传学状态不利的患者无病生存期（DFS）明显较差（P = 0.002），但与疾病状态无显著相关性（P = 0.43）。这些数据表明，某些继发性染色体畸变[+8，i(17q)，Ph重复]应重新分类为CML中BMT成功的相对有利预测指标，因此应与耐药疾病特有的不利细胞遗传学畸变[-7，inv(3)，复杂核型]区分开来。患者数量有限，无法对任何单一诊断的特定细胞遗传学畸变的预后意义进行明确评估。然而，这些发现表明细胞遗传学状态可能是预测异基因骨髓移植后结果的一个重要且独立的因素。
