A clinical study of MRD-based therapy for childhood ALL

基于 MRD 的儿童 ALL 治疗的临床研究

• 批准号: 12671002
• 负责人: YOKOYA Shohei
• 金额: $ 2.05万
• 依托单位: Kyoto Prefectural University of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671002/
• 关键词: minimal residual disease; acute lymphoblastic leukemia; childhood leukemia; chemotherapy; T-cell receptor gene; immunoglobulin chaingene; 微小残存病変; 免疫グロブリン遺伝子; PCR

The purpose of this research project is to inprove the cure rate and the QOL of the childhood ALL via a novel strategy of leukemia-therapy which is based on the minimal residual disease in early phase of chemotherapy.We started the protocol in February 2000. By the end of December 2002, 214 children with ALL have been enroled in the project. All of them were stratified into 4 groups, HHR (high-high-risk, 23 patients), HR (high-risk, 82 patients), IR (intermediate-risk, 48 patients), and LR (low-risk 61 patients), according to the age and white blood counts at diagnosis. In 186 patients (80%), we could find clonal recombination of either TCR gamma (48 patients), TCR delta (44 patients), Ig kappa (43 patients), or heavy chain (32 patients) gene which was suitable for the targets of PCR amplification. We could quantitate the MRD in the bone marrow in 161 patients 4 weeks (point 1) and 12 weeks (point 2) after the initiation of therapy. BM-MRD were positive in point 1, point2, and both points in 67 patients (36%), 36 patients (19.4%), and 34 patients (18.3%), respectively. Positive rates in both points were 18%, 16.4%, 7.3% and 58% in LR, IR, HR, and HHR-group, respectively. 2-years event-free survival (EFS) of the whole patients is 91.4%. It is too early to draw any conclusion concerning the relevance between MRD and prognosis

该研究项目的目的是通过一种新颖的白血病治疗策略来侵蚀治愈率和童年的质量，该策略基于化学疗法早期的最小残留疾病。我们于2000年2月开始了该方案。 2002年12月底，有214名有所有的儿童参加了该项目。所有这些都分为4组HHR（高风险，23名患者），人力资源（高风险，82例），IR（中等风险，48例患者）和LR（低风险61例） ，根据诊断时的年龄和白血计数。在186名患者（80％）中，我们可以找到TCR伽马（48例患者），TCR三角洲（44例患者），IG KAPPA（43例患者）或重链（32例患者）基因的克隆重组。 PCR扩增。在开始治疗后，我们可以在161例4周（点1）和12周（点2）中对骨髓中的MRD进行定量。 BM-MRD分别为67名患者（36％），36例（19.4％）和34例患者（18.3％）的BM-MRD呈阳性。这两个点的正率分别为LR，IR，HR和HHR组的18％，16.4％，7.3％和58％。整个患者的2年无事件生存期（EFS）为91.4％。现在就MRD和预后之间的相关性得出任何结论还为时过早

项目成果

Okamoto T, Yokota S, Katano N, Seriu T, Nakao M, Taniwaki M, Watanabe A, Asami K, Kikuta A, Koizumi S, Kawakami T, Ohta S, Miyake M, Watanabe T, Iwai A, Kamitamari A, Ijichi O, Hyakuna N, Mimaya J, Fujimoto T, Tsurusawa M: "Minimal residual disease in ear

冈本 T、横田 S、片野 N、Seriu T、中尾 M、谷胁 M、渡边 A、麻美 K、菊田 A、小泉 S、川上 T、太田 S、三宅 M、渡边 T、岩井 A、神魂 A、Ijichi O

横田 昇平: "末梢血幹細胞移植の実際"南江堂. 27 (2001)

Shohei Yokota：“外周血干细胞移植的实践”Nankodo 27（2001）。

Tamura A, Miura I, Iida S, Yokota S, Horiike S, et al.: "Interphase detection of immunoglobulin heavy chain gene translocations with specific oncogene loci in 173 patients with B-cell lymphoma"Cancer Genet Cytogenet. 129(1). 1-9 (2001)

Tamura A、Miura I、Iida S、Yokota S、Horiike S 等人：“173 例 B 细胞淋巴瘤患者中具有特定癌基因位点的免疫球蛋白重链基因易位的间期检测”Cancer Genet Cytogenet。

Kimura T, Wang J, Minamiguchi H, Fujiki H, Harada S, Okuda K, Kaneko H, Yokota S, Yasukawa K, Abe T, Sonoda Y: "Signal through gp130 activated by soluble interleukin (IL)-6 receptor R and IL-6 or IL-6R/IL-6 fusion protein enhances Ex vivo expansion of hum

Kimura T、Wang J、Minamiguchi H、Fujiki H、Harada S、Okuda K、Kaneko H、Yokota S、Yasukawa K、Abe T、Sonoda Y：“通过可溶性白介素 (IL)-6 受体 R 和 IL 激活的 gp130 的信号

Fujiki H, Kimura T, Minamiguchi H, Harada S, Wang J, Nakao M, Yokota S, Urata Y, Ueda Y, Yamagishi H, Sonoda Y: "Role of human interleukin-9 as a megakaryo-cyte potentiator in culture"Exp Hematol. 30. 1373-1380 (2002)

Fujiki H、Kimura T、Minamiguchi H、Harada S、Wang J、Nakao M、Yokota S、Uurata Y、Ueda Y、Yamagishi H、Sonoda Y：“人白细胞介素 9 作为巨核细胞增强剂在培养中的作用”Exp