强化交替药物组合治疗高危儿童急性淋巴细胞白血病。一项儿科肿瘤学组的试点研究。

Intensive alternating drug pairs for treatment of high-risk childhood acute lymphoblastic leukemia. A Pediatric Oncology Group pilot study.

作者信息

Lauer S J, Camitta B M, Leventhal B G, Mahoney D H, Shuster J J, Adair S, Casper J T, Civin C I, Graham M, Kiefer G

机构信息

Department of Pediatrics, Midwest Children's Cancer Center, Medical College of Wisconsin, Milwaukee.

出版信息

Cancer. 1993 May 1;71(9):2854-61. doi: 10.1002/1097-0142(19930501)71:9<2854::aid-cncr2820710929>3.0.co;2-j.

DOI:10.1002/1097-0142(19930501)71:9<2854::aid-cncr2820710929>3.0.co;2-j

PMID:8467463

Abstract

BACKGROUND

To prevent drug resistance, the authors designed a protocol that featured early intensive rotating drug pairs as part of the therapy for acute lymphoblastic leukemia (ALL).

METHODS

After prednisone, vincristine, asparaginase, and daunorubicin induction, 12 intensive treatments (ABACABACABAC) were given in 30 weeks: A--intermediate-dose methotrexate (IDMTX) plus intermediate-dose mercaptopurine (MP); B--cytosine arabinoside (AC) plus daunorubicin (DNR); C--AC plus teniposide (VM-26). Triple intrathecal chemotherapy (AC, MTX, and hydrocortisone) was given for central nervous system (CNS) prophylaxis. Continuation therapy consisted of weekly MTX and daily MP until 2.5 years of continuous complete remission had been achieved.

RESULTS

Seventy-four children (age range, 1-19 years) at high risk of relapse were treated. Of 55 with B-lineage (early pre-B, pre-B) ALL, 24 have failed (2 induction failures, 2 deaths from infection, and 20 relapses). The event-free survival (EFS) rate at 4 years was 55.5% (standard error [SE] +/- 7.7%). Of 19 patients with T-cell ALL, 12 have failed (2 induction failures and 10 relapses). The EFS rate at 4 years was 32.6% (SE +/- 26.8%). Toxicities were significantly more common after AC and DNR or AC and VM-26 than IDMTX and MP. There were no toxicity-related deaths during intensive treatments.

CONCLUSION

Early intensive rotating therapy is tolerable and warrants consideration for additional trials of patients with high-risk, B-lineage ALL.

摘要

背景

为预防耐药性，作者设计了一种方案，其特点是将早期强化轮换药物组合作为急性淋巴细胞白血病（ALL）治疗的一部分。

方法

在泼尼松、长春新碱、天冬酰胺酶和柔红霉素诱导治疗后，在30周内给予12次强化治疗（ABACABACABAC）：A——中剂量甲氨蝶呤（IDMTX）加中剂量巯嘌呤（MP）；B——阿糖胞苷（AC）加柔红霉素（DNR）；C——AC加替尼泊苷（VM - 26）。给予三联鞘内化疗（AC、甲氨蝶呤和氢化可的松）用于中枢神经系统（CNS）预防。维持治疗包括每周一次甲氨蝶呤和每日一次巯嘌呤，直至实现2.5年持续完全缓解。

结果

对74例有高复发风险的儿童（年龄范围1 - 19岁）进行了治疗。在55例B系（早前B、前B）ALL患者中，24例治疗失败（2例诱导失败、2例死于感染和20例复发）。4年无事件生存率（EFS）为55.5%（标准误[SE]±7.7%）。在19例T细胞ALL患者中，12例治疗失败（2例诱导失败和10例复发）。4年EFS为32.6%（SE±26.8%）。AC与DNR或AC与VM - 26联合治疗后的毒性明显比IDMTX与MP联合治疗更常见。强化治疗期间无毒性相关死亡。