Cortes Jorge, Talpaz Moshe, O'Brien Susan, Giles Francis, Beth Rios Mary, Shan Jianquin, Faderl Stefan, Garcia-Manero Guillermo, Ferrajoli Alessandra, Wierda William, Kantarjian Hagop
Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Cancer. 2003 Sep 15;98(6):1105-13. doi: 10.1002/cncr.11629.
Older age is a consistent poor prognostic factor in patients with Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML). Whether this is related to an intrinsic worse disease biology or to inadequate drug delivery or excessive treatment-associated toxicity is unknown. The availability of imatinib mesylate, a selective, Bcr-Abl-targeted therapy that is administered orally with minimal side effects, may clarify whether older age would remain an adverse factor (thus, implying a different age-related CML biology).
Seven hundred forty-seven patients in different phases of Ph-positive CML who were treated with imatinib from 1999 until the time of last follow-up were evaluated. Among them, 187 patients had newly diagnosed, early chronic phase CML; 351 patients had chronic phase CML after interferon alpha (IFN) failure; 133 patients had accelerated phase CML; and 76 patients had blastic phase CML. The imatinib daily dose varied from 400 mg to 800 mg orally, according to the protocol design. Patients were categorized into a group of older patients (age 60 years or older) or younger patients (age younger than 60 years). Their characteristics, responses to therapy, and survival were compared by univariate and multivariate analyses.
One hundred eighty-seven patients had newly diagnosed CML, and 49 patients (26%) were in the older age group. Older patients had similar cytogenetic response rates and survival compared with younger patients. Among 351 patients with late chronic phase CML after IFN failure, 120 patients (34%) were in the older age group. Although the older patients had a lower incidence of achievement of complete cytogenetic response (Ph, 0%) by univariate analysis (56% vs. 44%; P = 0.05), age was not found to be an independent poor prognostic factor in the multivariate analysis. Similarly, older age was not an adverse poor prognostic factor for survival. Forty-two of 133 patients (32%) with accelerated phase CML were older. The incidence of any cytogenetic response was lower in older patients (53% vs. 33%; P = 0.04), but age was not significant in the multivariate analysis. Older patients also had a trend toward worse survival (P = 0.09) that was not significant in the multivariate analysis. Twenty-eight of 76 patients (37%) evaluated in blastic phase were older. Older age was not a significant prognostic factor either for achieving response or for survival.
With imatinib therapy, older age appears to have lost much of its prognostic relevance. This suggests that the previous poor prognosis observed with older age was related to treatment-associated factors (e.g., toxicity with allogeneic transplantation or with IFN therapy) rather than to an intrinsic, different disease biology of CML in older patients.
在费城染色体（Ph）阳性慢性髓性白血病（CML）患者中，高龄一直是预后不良的因素。这是与内在的更差疾病生物学特性有关，还是与药物递送不足或过度的治疗相关毒性有关，目前尚不清楚。甲磺酸伊马替尼的出现，这是一种选择性的、靶向Bcr - Abl的疗法，口服给药且副作用极小，可能会阐明高龄是否仍将是一个不利因素（因此，意味着存在与年龄相关的不同CML生物学特性）。
对1999年至最后一次随访期间接受伊马替尼治疗的747例处于不同阶段的Ph阳性CML患者进行了评估。其中，187例患者为新诊断的早期慢性期CML；351例患者为干扰素α（IFN）治疗失败后的慢性期CML；133例患者为加速期CML；76例患者为急变期CML。根据方案设计，伊马替尼的每日口服剂量从400mg到800mg不等。患者被分为老年患者组（年龄60岁及以上）或年轻患者组（年龄小于60岁）。通过单因素和多因素分析比较了他们的特征、对治疗的反应和生存率。
187例患者为新诊断的CML，其中49例（26%）属于老年患者组。老年患者与年轻患者相比，具有相似的细胞遗传学反应率和生存率。在351例IFN治疗失败后的晚期慢性期CML患者中，120例（34%）为老年患者组。尽管单因素分析显示老年患者完全细胞遗传学反应（Ph，0%）的发生率较低（56%对44%；P = 0.05），但在多因素分析中，年龄并未被发现是独立的不良预后因素。同样，高龄也不是生存的不良预后因素。133例加速期CML患者中有42例（32%）为老年患者。老年患者的任何细胞遗传学反应发生率较低（53%对33%；P = 0.04），但在多因素分析中年龄并不显著。老年患者的生存趋势也较差（P = 0.09），但在多因素分析中并不显著。在76例接受评估的急变期患者中有28例（37%）为老年患者。高龄对于实现反应或生存均不是显著的预后因素。
使用伊马替尼治疗后，高龄似乎已失去其大部分预后相关性。这表明先前观察到的高龄患者预后不良与治疗相关因素（例如，异基因移植或IFN治疗的毒性）有关，而不是与老年患者内在的、不同的CML疾病生物学特性有关。
