风险导向治疗后急性淋巴细胞白血病患儿的低复发率

Low relapse rate in children with acute lymphoblastic leukemia after risk-directed therapy.

作者信息

Tzortzatou-Stathopoulou F, Papadopoulou A L, Moschovi M, Botsonis A, Tsangaris G T

机构信息

First Department of Pediatrics, University of Athens, Aghia Sophia Children's Hospital, Greece.

出版信息

J Pediatr Hematol Oncol. 2001 Dec;23(9):591-7. doi: 10.1097/00043426-200112000-00008.

DOI:10.1097/00043426-200112000-00008

PMID:11902303

Abstract

PURPOSE

Even though acute lymphoblastic leukemia (ALL) responds well to chemotherapy, relapse remains the major problem. This study documents relapse and survival rates in 85 consecutive children (33 at good risk, 52 at high risk) with ALL diagnosed in 1991 to 1996.

PATIENTS AND METHODS

Until 1993, the New York II protocol for the high-risk group and a combination of UKALL XI (induction) and R blocks of ALL-REZ BFM-87 (intensification) regimens for patients at good risk were used. To reduce toxicity, the protocols were subsequently modified. Consolidation treatment was the same for both groups, consisting of a lower cytarabine dose and methotrexate removal, whereas intensification was changed only for the high-risk group using the BB block of the NHL-BFM-90 protocol. The bone marrow clearance of leukemia was assessed on day 22, and minimal residual disease was detected using polymerase chain reaction analysis of Ig heavy-chain gene rearrangements.

RESULTS

Seventy patients had common precursor B lineage ALL, six had pre-B-ALL, eight had T-ALL, and one had B-ALL. Two patients never achieved remission and died. Six patients died of consolidation-related complications. Four more patients died, two during induction and two during maintenance therapy. Two other children had relapse (2.3%), both of whom were treated with the earlier protocols and then underwent bone marrow transplantation. Four more children with morphologically complete remission showed minimal residual disease (which reached the levels of 1 leukemic cell among 10(2)-10(4) normal cells) with the use of clone-specific probes at several points of the study intervals, but never had relapse. The 5-year overall and event-free survival rates were 86% and 83%, respectively. The 5-year overall survival rates for good-risk and high-risk groups were 94% and 81%; the corresponding event-free rates were 91% and 78%. The 5-year event-free survival rate in the patients at high risk was significantly higher after the protocol change (90% vs. 65%, P = 0.04).

CONCLUSIONS

The modification proved to be effective in diminishing the therapeutic toxicity and improving the efficacy, mainly for the high-risk group.

摘要

目的

尽管急性淋巴细胞白血病（ALL）对化疗反应良好，但复发仍是主要问题。本研究记录了1991年至1996年确诊的85例连续ALL患儿（33例低危，52例高危）的复发率和生存率。

患者与方法

直到1993年，高危组采用纽约II方案，低危患者采用UKALL XI（诱导）和ALL-REZ BFM-87方案的R块（强化）联合方案。为降低毒性，随后对方案进行了修改。两组的巩固治疗相同，包括降低阿糖胞苷剂量和去除甲氨蝶呤，而强化治疗仅对高危组进行了改变，采用NHL-BFM-90方案的BB块。在第22天评估白血病的骨髓清除情况，并使用Ig重链基因重排的聚合酶链反应分析检测微小残留病。

结果

70例为普通前体B系ALL，6例为前B-ALL，8例为T-ALL，1例为B-ALL。2例患者从未达到缓解并死亡。6例患者死于巩固治疗相关并发症。另有4例患者死亡，2例在诱导期，2例在维持治疗期。另有2例儿童复发（2.3%），均接受了早期方案治疗，然后进行了骨髓移植。在研究期间的几个时间点，另外4例形态学完全缓解的儿童使用克隆特异性探针显示微小残留病（达到每10（2）-10（4）个正常细胞中有1个白血病细胞的水平），但从未复发。5年总生存率和无事件生存率分别为86%和83%。低危组和高危组的5年总生存率分别为94%和81%；相应的无事件生存率分别为91%和78%。方案改变后，高危患者的5年无事件生存率显著提高（90%对65%，P = 0.04）。