儿童B细胞急性淋巴细胞白血病风险适应性治疗的长期结果：日本儿童白血病研究协会ALL-97试验报告

Long-term Results of the Risk-adapted Treatment for Childhood B-Cell Acute Lymphoblastic Leukemia: Report From the Japan Association of Childhood Leukemia Study ALL-97 Trial.

作者信息

Horibe Keizo, Yumura-Yagi Keiko, Kudoh Tooru, Nishimura Shinichiro, Oda Megumi, Yoshida Makoto, Komada Yoshihiro, Hara Junichi, Tawa Akio, Usami Ikuya, Tanizawa Akihiko, Kato Koji, Kobayashi Ryoji, Matsuo Keitaro, Hori Hiroki

机构信息

*Clinical Research Center, National Hospital Organization Nagoya Medical Center ∥∥Department of Hematology and Oncology, Children's Medical Center, Japanese Red Cross Nagoya First Hospital ##Division of Molecular Medicine, Aichi Cancer Center, Nagoya †Department of Pediatrics, Osaka General Medical Center **Department of Pediatric, Osaka City General Hospital ††Department of Pediatric Hematolgy/Oncology, National Hospital Organization Osaka Medical Center, Osaka ‡Department of Pediatrics, Hokkaido Medical Center for Child Health and Rehabilitation ¶¶Department of Pediatrics, Hokkaido University Graduate School of Medicine, Sapporo §Hiroshima University Hospital, Hiroshima ∥Department of Pediatrics, Okayama University Hospital, Okayama ¶Department of Pediatrics, Asahikawa Medical College Hospital, Asahikawa #Department of Pediatrics, Mie University Hospital, Tsu ‡‡Department of Pediatrics, Kobe City Medical Center General Hospital, Kobe §§Department of Pediatrics, University of Fukui, Fukui, Japan.

出版信息

J Pediatr Hematol Oncol. 2017 Mar;39(2):81-89. doi: 10.1097/MPH.0000000000000760.

DOI:10.1097/MPH.0000000000000760

PMID:28169879

Abstract

PURPOSE

This study was conducted as the first clinical trial by Japan Association of Childhood Leukemia Study to improve the outcome of B-cell acute lymphoblastic leukemia and explore a less toxic reinduction block.

PATIENTS AND METHODS

From 1997 to 2002, 563 patients with B-cell acute lymphoblastic leukemia aged 1 to 15 years were enrolled. The patients were assigned into 4 risk groups (standard, intermediate, high, or extremely high risk) and treated with regimens intensified according to the risk. Two randomized trials were conducted to compare 2 regimens with and without a 3-week reinduction therapy in the standard-risk group, and to compare the efficacy of pirarubicin with daunorubicin in the intermediate-risk and high-risk groups. Prophylactic cranial irradiation was restricted in patients with high or extremely high risk.

RESULTS

The event-free survival (EFS) rate at 10 years for all patients was 77.0%. Those in the standard-risk to extremely high-risk groups were 79.3%, 72.5%, 71.7%, and 66.3%, respectively. The 15-week induction/consolidation not followed by reinduction produced 76.4% of the EFS at 10 years comparable with the regimen with reinduction therapy. Pirarubicin at 25 mg/m administered 11 times throughout the treatment produced the EFS comparable with daunorubicin at 30 mg/m.

CONCLUSION

The trial produced high survival rates in NCI-HR patients, although the outcomes in NCI-SR patients were not satisfactory possibly due to less intensive central nervous system-directed therapy.

摘要

目的

本研究是日本儿童白血病研究协会开展的第一项临床试验，旨在改善B细胞急性淋巴细胞白血病的治疗效果，并探索毒性较小的再诱导方案。

患者与方法

1997年至2002年，纳入了563例年龄在1至15岁的B细胞急性淋巴细胞白血病患者。这些患者被分为4个风险组（标准、中危、高危或极高危），并根据风险接受强化治疗方案。进行了两项随机试验，以比较标准风险组中接受和不接受3周再诱导治疗的两种方案，并比较中危组和高危组中吡柔比星与柔红霉素的疗效。预防性颅脑照射仅限于高危或极高危患者。

结果

所有患者10年无事件生存率（EFS）为77.0%。标准风险组至极高风险组的患者分别为79.3%、72.5%、71.7%和66.3%。15周诱导/巩固治疗后不进行再诱导治疗，10年EFS率为76.4%，与再诱导治疗方案相当。在整个治疗过程中11次给予25mg/m²的吡柔比星，其EFS与30mg/m²的柔红霉素相当。