Hirst W J, Mufti G J
Department of Haematological Medicine, King's College Hospital School of Medicine and Dentistry, London, U.K.
Leuk Res. 1994 Nov;18(11):797-804. doi: 10.1016/0145-2126(94)90158-9.
The use of intensive chemotherapy in the treatment of myelodysplastic syndromes (MDS) has met with some disappointment, although subgroups of patients have been identified in which the response approaches that of de novo acute myeloid leukaemia (AML). We hypothesized that it is not the FAB classification per se, but the biological behaviour of the blasts as shown by their rate of accumulation that influences the response. We have, therefore, included AML with trilineage dysplasia (AML/TLD) as it represents one extreme of the evolution of MDS to AML. We have analysed the results of intensive chemotherapy in 22 patients (median age 60 years; range 26-77 years) with MDS (14) and AML/TLD (8). Response to treatment was analysed by age, interval from diagnosis to treatment, the number of cytopenias, bone marrow blasts and karyotype. Patients were also divided according to the rate of disease progression, shown by the time from diagnosis to treatment (group A = < 3 months; group B = > 3 months). The overall response rate was 87%; 13 (60%) complete responses (CR) and 6 (27%) partial responses. The rate of disease progression was identified as the most significant predictive factor of achieving CR (p = 0.003) (group A 10/12; group B 3/10). Patients presenting with more than 20% blasts also had a better response (p = 0.031). The combined response rates, however, did not differ significantly between the two groups (group A 92%; group B 80%) as 50% of group B achieved a PR. The failure to normalize blood counts was not related to the number of cytopenias before starting treatment. In all cases, PR was associated with persistence of dysplastic morphology and cytogenetic abnormalities. CR was associated with complete morphological and cytogenetic response except in two patients in group B. Dysplastic morphology re-emerged in patients who achieved CR and of these, all but one acquired a new cytogenetic abnormality. Patients in group B who achieved CR all needed two courses compared with a mean of 1.1 for the other group. The median survival from treatment for both groups was 10 months, however, no patient in group B survived more than 20 months. In comparison 33% in group A were alive at 5 years. The rate of accumulation of blasts predicts the response to chemotherapy and the quality of remissions achieved. Patients with rapidly increasing blasts can achieve complete morphological and cytogenetic remissions, although they eventually have a dysplastic relapse. In contrast, intensive chemotherapy for patients with a slow accumulation of blasts may reduce the blast population but with much less benefit on haemopoiesis.(ABSTRACT TRUNCATED AT 400 WORDS)
尽管已确定部分患者亚组对强化化疗的反应接近初发急性髓系白血病（AML），但强化化疗在骨髓增生异常综合征（MDS）治疗中的应用效果却不尽人意。我们推测，影响反应的并非FAB分类本身，而是原始细胞的生物学行为，如它们的积聚速率所示。因此，我们纳入了伴有三系发育异常的AML（AML/TLD），因为它代表了MDS向AML演变的一个极端情况。我们分析了22例患者（中位年龄60岁；范围26 - 77岁）强化化疗的结果，其中MDS患者14例，AML/TLD患者8例。通过年龄、从诊断到治疗的间隔时间、血细胞减少的数量、骨髓原始细胞以及核型来分析治疗反应。患者还根据疾病进展速率进行分组，以从诊断到治疗的时间表示（A组 = < 3个月；B组 = > 3个月）。总体缓解率为87%；13例（60%）完全缓解（CR），6例（27%）部分缓解。疾病进展速率被确定为实现CR的最显著预测因素（p = 0.003）（A组10/12；B组3/10）。原始细胞超过20%的患者也有更好的反应（p = 0.031）。然而，两组的联合缓解率差异不显著（A组92%；B组80%），因为B组50%的患者达到部分缓解。血细胞计数未恢复正常与开始治疗前血细胞减少的数量无关。在所有病例中，部分缓解与发育异常形态学和细胞遗传学异常的持续存在相关。完全缓解与完全的形态学和细胞遗传学反应相关，但B组有2例患者除外。达到CR的患者中发育异常形态学再次出现，其中除1例患者外，所有患者均获得了新的细胞遗传学异常。B组达到CR的患者均需要两个疗程，而另一组的平均疗程为1.1个。两组治疗后的中位生存期均为10个月，然而，B组没有患者存活超过20个月。相比之下，A组33%的患者5年后仍存活。原始细胞的积聚速率可预测化疗反应及所达到的缓解质量。原始细胞快速增加的患者可实现完全的形态学和细胞遗传学缓解，尽管他们最终会出现发育异常复发。相反，对原始细胞积聚缓慢的患者进行强化化疗可能会减少原始细胞数量，但对造血的益处要小得多。（摘要截选至400字）
