FACTORS THAT INFLUENCE HAEMATOLOGICAL REMISSION DURATION IN ACUTE LYMPHOCYTIC LEUKAEMIA
FACTORS THAT INFLUENCE HAEMATOLOGICAL REMISSION DURATION IN ACUTE LYMPHOCYTIC LEUKAEMIA
复制标题
影响急性淋巴细胞白血病血液学缓解持续时间的因素
DOI：
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发表时间：
1976
影响因子：
6.5
通讯作者：
J. Simone
中科院分区：
文献类型：
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作者：
J. Simone
急性 1 淋巴细胞白血病 (ALL) 的现代疗法可以使 90% 以上的儿童得到缓解并预防明显的中枢神经系统 (CNS) 白血病（Simone，1974）。缓解的质量和持续时间得到如此改善，以至于相当一部分患者可以安全地停止治疗（Aur 等，1974）。尽管取得了这些进展，但目前对 ALL 的治疗仍有很多不足之处。现代治疗是复杂的、昂贵的并且很大程度上是经验性的；它的副作用从仅仅令人烦恼到危及生命；它具有潜在的致癌性，并可能对性腺、肝脏、神经系统和心脏等器官产生潜在的功能影响。然而，现代治疗面临的最严重的直接问题是它无法预防三分之一到三分之二患者的血液学复发。当当时接受化疗的患者出现血液学复发时，生存的机会实际上就被消除了。尽管预防或延缓血液学复发的理想疗法尚不清楚，但已经制定了有用的指南。研究已清楚地确定了缓解期间继续治疗的必要性（Freireich 等，1964）、间歇性甲氨蝶呤给药优于每日甲氨蝶呤给药（急性白血病 B 组，1965）以及给予最大耐受剂量化疗的价值（Pinkel 等，1971）。虽然甲氨蝶呤和巯嘌呤是延长血液学缓解的最有效药物，但对照研究未能确定同时、顺序或循环联合用药的显着优势（Frei 等，1961；澳大利亚研究组，1968；Krivit 等，1968）。在一些研究中，添加其他化疗药物延长了缓解期（Holland & Glidewell，1972；Leikin 等人，1969；Pinkel，1971；Haghbin 等人，1974），而在其他研究中却没有延长缓解期（Aur 等人，1972；Sackman Muriel 等人，1974；Simone 等人，197~a,b）。然而，由于还没有出现足够有效的治疗方案来成为标准，因此缓解期间的治疗组合需要定期重新检查（Simone，I 974）。本注释提供了该医院连续四项 ALL“全面治疗”研究中影响血液学缓解持续时间的因素分析的新数据，并试图解释一项研究中较差的结果。如表I所示，所有研究均采用多药治疗，并且在研究V（Aur等人，1971a）之后，通过研究VI（Aur等人，1972）、VII（Aur等人，1973）和VIII（S'imone，1974；Simone等人，1975a，b）中的随机化测试了一系列修改。除研究 VIII 中随机接受单独甲氨蝶呤治疗的 20 名患者外，所有获得血液学缓解的患者均纳入研究之间的比较；过度的神经毒性需要尽早终止该肢体（Simone 等人，197sa）。为了量化每项研究和亚组的血液学复发率，通过最小二乘法从每隔 6 个月保持血液学缓解的患者比例得出回归系数。研究 V-VII 中的分析仅限于 24 个月，因为大多数复发发生在这段时间，并且斜率随后变为
Modern therapy for acute 1 ymphocytic leukaemia (ALL) induces remission and prevents evident central nervous system (CNS) leukaemia in over 90% of children (Simone, 1974). The quality and duration of remission has so improved that therapy may be stopped safely in a significant proportion of patients (Aur et al , 1974). Despite these advances, the current treatment of ALL leaves much to be desired. Modern therapy is complex, costly and largely empirical; it has side effects ranging from merely annoying to life-threatening ; it is potentially carcinogenic and may have latent functional effects on organs such as the gonads, liver, nervous system and heart. The most serious immediate problem facing modern therapy, however, is its inability to prevent haematological relapse in one-third to two-thirds of patients. When haematological relapse occurs in patients receiving chemotherapy at the time, the chance for survival is virtually eliminated. Although the ideal therapy for preventing or delaying haematological relapse is unknown, useful guidelines have been developed. Studies have clearly established the necessity of continuing therapy during remission (Freireich et al, 1964), the superiority of intermittent over daily methotrexate administration (Acute Leukemia Group B, 1965) and the value of giving maximum-tolerated doses of chemotherapy (Pinkel et al , 1971). While methotrexate and mercaptopurine have been the most effective agents for prolonging haematological remission, controlled studies failed to establish the substantial superiority of simultaneous, sequential or cyclic combinations (Frei et al , 1961; Australian Study Group, 1968; Krivit et al , 1968). The addition of other chemotherapeutic agents prolonged remission in some studies (Holland & Glidewell, 1972; Leikin et al , 1969; Pinkel, 1971; Haghbin et al, 1974) and not in others (Aur et a l , 1972; Sackman Muriel et al , 1974; Simone et al , 197~a, b). However, since no regimen has emerged with sufficient efficacy to become standard, the composition of therapy during remission requires periodic re-examination (Simone, I 974). This annotation presents new data from an analysis of factors influencing haematological remission duration in four consecutive ‘total therapy’ studies of ALL at this hospital and attempts to explain the inferior results in one study. As shown in Table I, all studies employed multiple-agent therapy and, after Study V (Aur et a/, 1971a), a series of modifications was tested by randomization in Studies VI (Aur et al, 1972), VII (Aur et a!, 1973) and VIII (S’ imone, 1974; Simone et al, 1975a, b). All patients who attained haematological remission are included in the comparisons between studies except the 20 patients in study VIII randomized to receive methotrexate alone; excessive neurotoxicity required early termination of this limb (Simone et al, 197sa). To quantify the haematological relapse rate for each study and subgroup, the regression coefficient was derived by the least squares method from the proportion of patients remaining in haematological remission at 6 month intervals. Analysis is limited to 24 months in Studies V-VII because most relapses occur during this time and the slopes subsequently become