Chiu E K, Chan L C, Liang R, Lie A, Kwong Y L, Todd D, Chan T K
Department of Medicine, University of Hong Kong, Queen Mary Hospital.
Leukemia. 1994 Sep;8(9):1469-73.
Fifty consecutive adult patients with acute lymphoblastic leukemia (ALL) were treated with an intensive cyclical chemotherapy and the mean received dose of individual cytotoxic drug was retrospectively studied. The median age was 28 years. Twenty-one (43%) had white blood cell (WBC) count over 30 x 10(9)/l. Of the 26 patients with successful cytogenetic studies, ten (28%) had unfavorable clonal chromosomal abnormalities (four Philadelphia chromosome, six others). A high complete remission (CR) rate (86%) was achieved. This was associated with delivery of 100% of the planned dosage of vincristine, prednisone, and daunorubicin at induction. Dose reduction of asparaginase, the fourth drug in the induction protocol, was recorded in 20 (40%) patients. The CR rate of these patients was not adversely affected. Dose reduction was recorded during consolidation (38 of 43 remitters) and maintenance (18 of 20 remitters) as a result of treatment toxicity. The mean received dose of teniposide, Ara-C, asparaginase, mercaptopurine, and methotrexate was 73% (SD 7%), 73% (SD 7%), 62% (SD 41%), 65% (SD 15%) and 73% (SD 17%) of the planned dosage, respectively. The 5-year overall survival and leukemia-free survival (LFS) were 11% (95% CI: 0-27%) and 13% (95% CI: 0-26%), respectively. Even standard-risk patients had 4-year LFS of only 26% (95% CI: 0-57%). Among 36 remitters not withdrawn from consolidation, there were 29 treatment failures after a median follow-up of 42 months; 25 (86%) of these were leukemia relapse, three (10%) were toxic death during consolidation, and one patient (4%) died from therapy-related myelodysplastic syndrome. We postulate inadequate drug delivery during postremission therapy contributed to the high relapse rate in the whole group as well as the standard-risk patients.
连续50例成年急性淋巴细胞白血病（ALL）患者接受了强化周期性化疗，并对个体细胞毒性药物的平均接受剂量进行了回顾性研究。中位年龄为28岁。21例（43%）患者白细胞（WBC）计数超过30×10⁹/L。在26例成功进行细胞遗传学研究的患者中，10例（28%）存在不良克隆性染色体异常（4例费城染色体，6例其他异常）。实现了较高的完全缓解（CR）率（86%）。这与诱导期长春新碱、泼尼松和柔红霉素100%的计划剂量给药有关。诱导方案中的第四种药物天冬酰胺酶有20例（40%）患者出现剂量减少。这些患者的CR率未受到不利影响。由于治疗毒性，巩固期（43例缓解者中的38例）和维持期（20例缓解者中的18例）均记录到剂量减少。替尼泊苷、阿糖胞苷、天冬酰胺酶、巯嘌呤和甲氨蝶呤的平均接受剂量分别为计划剂量的73%（标准差7%）、73%（标准差7%）、62%（标准差41%）、65%（标准差15%）和73%（标准差17%）。5年总生存率和无白血病生存率（LFS）分别为11%（95%CI：0 - 27%）和13%（95%CI：0 - 26%）。即使是标准风险患者，4年LFS也仅为26%（95%CI：0 - 57%）。在36例未退出巩固治疗的缓解者中，中位随访42个月后有29例治疗失败；其中25例（86%）为白血病复发，3例（10%）为巩固期毒性死亡，1例患者（4%）死于治疗相关的骨髓增生异常综合征。我们推测缓解后治疗期间药物给药不足导致了整个组以及标准风险患者的高复发率。
