Mechanisms of Treatment Failure in Childhood Acute Lymphoblastic Leukemia: Children’s Cancer Group Initiatives
Mechanisms of Treatment Failure in Childhood Acute Lymphoblastic Leukemia: Children’s Cancer Group Initiatives
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儿童急性淋巴细胞白血病治疗失败的机制：儿童癌症小组倡议
DOI：
10.1007/978-3-642-60377-8_95
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
F. Uckun
中科院分区：
文献类型：
--
作者：
P. Gaynon;B. Bostrom;G. Reaman;H. Sather;M. Trigg;D. Tubergen;F. Uckun
自1968年以来，儿童癌症小组（CCG）对新诊断的急性淋巴细胞白血病（ALL）儿童进行了临床试验，招募了12000多名儿童。仅1994年就有1000多名儿童入学。初步分析显示，CCG-1800系列的4年无事件生存率为74%，在过去两个系列的研究中，相对失败风险连续显著降低25%。从这一经验中可以得出几个主题，(a)对治疗的早期反应是结果的一致决定因素；(b)诱导后有效强化全身治疗可降低具有有利或不利表现特征的患者骨髓和髓外复发的可能性；(c)有效的症状前中枢神经系统治疗可提供给所有婴儿和大多数儿童，无需颅脑照射。然而，对于少数具有高风险表现特征的儿童，18 Gy的颅脑照射可能仍然有用。最近的观察表明，原发性疾病对化疗的耐药性和不利的宿主硫嘌呤药理学是治疗失败的共同机制。对化疗的抵抗可能与对细胞凋亡的抵抗有关。原发性疾病耐药的患者可通过体外试验或早期骨髓反应差来确定，并分配给更长期、更严格的强化治疗。我们建议采用终末诱导白血病负荷的实验室分析来衡量抗cd19美洲商陆抗病毒蛋白偶联物在已知耐药疾病复杂治疗中的特异性贡献。不能达到足够的细胞内硫嘌呤代谢物水平可能通过给药和/或用6-硫鸟嘌呤（6-TG）代替6-巯基嘌呤（6-MP）来纠正。费城染色体阳性ALL病例治疗失败的原因仍有待阐明。
The Children’s Cancer Group (CCG) has conducted clinical trials for children with newly diagnosed acute lymphoblastic leukemia (ALL) since 1968 and enrolled more than 12000 children. More than 1000 children were enrolled in 1994 alone. Prelimary analyses show a 4-years event-free survival of 74% for the current concluding CCG-1800 series and successive statistically significant 25% reductions in relative risk of failure over the last two series of studies. Several themes may be derived from this experience, (a) early response to therapy is a consistent determinant of outcome; (b) effective intensification of systemic therapy after induction reduces the likelihood of marrow and extramedullary relapse for patients with either favorable or unfavorable presenting features; (c) effective presymptomatic CNS therapy may be provided to all infants and most children without cranial irradiation. However, 18 Gy cranial irradiation may still be useful for a minority of children with higher-risk presenting features. Recent observations point to primary disease resistance to chemotherapy and unfavorable host thiopurine pharmacology as common mechanisms of treatment failure. Resistance to chemotherapy may be linked to resistance to apoptosis. Patients with primary disease resistance may be identified through in vitro assays or poor early marrow response and assigned to more prolonged, more rigorous intensification. We propose to employ laboratory assays of end-induction leukemic burden to measure the specific contribution of anti-CD 19 pokeweed antiviral protein conjugate in the context of complex therapy in known resistant disease. Failure to achieve adequate intracellular levels of thiopurine metabolites may possibly be redressed by parentheral administration and/or substitution of 6-thioguanine (6-TG) for 6-mercaptopurine (6-MP). The reasons for treatment failure in cases of Philadelphia chromosomepositive ALL remain to be elucidated.
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儿童急性淋巴细胞白血病中的费城染色体和 7 号单体：一项儿科肿瘤小组研究。
影响因子：
20.3
作者：
Russo,C;Carroll,A;Kohler,S;Borowitz,M;Amylon,M;Homans,A;Kedar,A;Shuster,J;Land,V;Crist,W
通讯作者：
Crist,W
严重联合免疫缺陷小鼠的人 t(4;11)(q21;q23) 急性淋巴细胞白血病。
影响因子：
20.3
作者：
Uckun,FM;Downing,JR;Chelstrom,LM;Gunther,R;Ryan,M;Simon,J;Carroll,AJ;Tuel-Ahlgren,L;Crist,WM
通讯作者：
Crist,WM
DOI：
10.1073/pnas.89.19.9005
发表时间：
1992-10-01
影响因子：
11.1
作者：
UCKUN, FM;TUELAHLGREN, L;SCHIEVEN, GL
通讯作者：
SCHIEVEN, GL
影响因子：
158.5
作者：
BARRETT, AJ;HOROWITZ, MM;GALE, RP
通讯作者：
GALE, RP
影响因子：
11.2
作者：
S. Sallan;S. Hitchcock-bryan;R. Gelber;J. Cassady;E. Frei;D. Nathan
通讯作者：
S. Sallan;S. Hitchcock-bryan;R. Gelber;J. Cassady;E. Frei;D. Nathan