Wetzler M, Dodge R K, Mrózek K, Carroll A J, Tantravahi R, Block A W, Pettenati M J, Le Beau M M, Frankel S R, Stewart C C, Szatrowski T P, Schiffer C A, Larson R A, Bloomfield C D
Roswell Park Cancer Institute, Buffalo, NY, USA.
Blood. 1999 Jun 1;93(11):3983-93.
The Cancer and Leukemia Group B (CALGB) has been conducting a prospective cytogenetic companion study (CALGB 8461) to all CALGB treatment protocols for newly diagnosed adults with acute lymphoblastic leukemia (ALL). These protocols underwent a significant change in 1988 when a new intensive chemotherapy program was introduced (CALGB 8811). We asked whether karyotype continued to represent a significant prognostic factor in adult ALL patients after the change. A total of 256 patients had adequate pretreatment cytogenetic analyses: 67 before 1988 and 189 subsequently. The complete remission (CR) rate for the whole group was 80%. Patients with t(9;22), t(4;11), -7, or +8 had significantly lower probabilities of continuous CR and survival at 5 years (.11 and.12) than patients with a normal karyotype (.38 and.37) and patients with miscellaneous cytogenetic abnormalities (.52 and.49; P <.001 for each comparison). When analyzed by treatment period, the CR rate before CALGB 8811 was 63%; subsequently, it was 86% (P <.001). Patients with cytogenetic abnormalities other than t(9;22), t(4;11), -7, or +8 had better CR rates, disease-free survival (DFS), and survivals (P =.001, P =.04, and P =.004, respectively) after the change to the more intensive chemotherapy regimens. Patients with normal cytogenetics had improved CR rate but no improved DFS or survival, whereas no significant benefit for patients with t(9;22), t(4;11), -7, or +8 was seen. In a multivariate analysis, karyotype retained its prognostic significance for DFS but not for survival; it remained the most important factor for DFS. We conclude that cytogenetic analysis at diagnosis should be used to guide treatment decisions in adults with ALL.
癌症与白血病B组（CALGB）一直在对所有针对新诊断的成年急性淋巴细胞白血病（ALL）患者的CALGB治疗方案进行一项前瞻性细胞遗传学配套研究（CALGB 8461）。1988年引入新的强化化疗方案（CALGB 8811）时，这些方案发生了重大变化。我们询问在这一变化之后，核型是否仍然是成年ALL患者的一个重要预后因素。共有256例患者进行了充分的预处理细胞遗传学分析：1988年之前有67例，之后有189例。整个组的完全缓解（CR）率为80%。与核型正常的患者（CR率为0.38，生存率为0.37）和有其他细胞遗传学异常的患者（CR率为0.52，生存率为0.49）相比，有t(9;22)、t(4;11)、-7或+8的患者持续CR和5年生存率显著更低（分别为0.11和0.12；每次比较P<0.001）。按治疗时期分析时，CALGB 8811之前的CR率为63%；之后为86%（P<0.001）。在改为更强化的化疗方案后，除t(9;22)、t(4;11)、-7或+8之外有细胞遗传学异常的患者有更好的CR率、无病生存期（DFS）和生存率（分别为P = 0.001、P = 0.04和P = 0.004）。核型正常的患者CR率有所提高，但DFS或生存率没有改善，而有t(9;22)、t(4;11)、-7或+8的患者未观察到显著获益。在多变量分析中，核型对DFS仍具有预后意义，但对生存率则不然；它仍然是DFS最重要的因素。我们得出结论，诊断时的细胞遗传学分析应用于指导成年ALL患者的治疗决策。
