Aricò Maurizio, Conter Valentino, Valsecchi Maria Grazia, Rizzari Carmelo, Boccalatte Marie France Pinta, Barisone Elena, Messina Chiara, De Rossi Giulio, Lo Nigro Luca, Pession Andrea, Locatelli Franco, Micalizzi Concetta, Basso Giuseppe
Oncoematologia Pediatrica, Ospedale dei Bambini G. Di Cristina, 90134 Palermo, Italy.
Haematologica. 2005 Sep;90(9):1186-91.
Treatment of childhood standard-risk (SR) acute lymphoblastic leukemia (ALL) is generally successful. However, intensive chemotherapy regimens may be associated with severe treatment sequelae. Efforts are therefore being made to identify those patients in whom less intensive treatment would be equally successful but cause fewer long-term sequelae. The aim of this study was to evaluate the efficacy of treatment reduction in a subset of children with ALL at minimal risk of failure.
The population of patients with SR ALL included children aged between 1 and 6 years with less than 20,000 WBC/mm3, non-T immunophenotype, DNA index between 1.16 and 1.6, absence of t(9;22) and t(4;11) clonal translocations, no extramedullary leukemia, good response to prednisone and complete remission (CR) at the end of induction therapy. A reduced-intensity, BFM-type treatment schedule (AIEOP-ALL 9501 protocol) was used. Induction therapy was based on vincristine, prednisone, L-asparaginase and intrathecal methotrexate only; high-dose-methotrexate (2 g/m2) was given x4. The BFM Protocol II was given as reinduction therapy; thus the total dose of anthracyclines was 120 mg/m2 and no epipodophyllotoxins or cranial irradiation were employed.
Between May 1995 and December 1999, 123 patients were identified as having SR-ALL (7.8% of the ALL-95 population), of whom 102 received the SR protocol. After a median follow-up of 5.9 years, 11 patients in the SR protocol had relapsed, 1 had died in remission, and 1 had developed a second malignant neoplasm. The probabilities (standard errors) of survival and event-free survival (EFS) were, respectively, 97.0% (1.7) and 86.7% (3.5) at 5 years, and 95.3% (2.4) and 86.7% (3.5) at 7 years.
Although most of the relapsed patients were rescued, the long-term EFS probability in this small, highly selected group of patients remains inferior to expectation. Thus, alternative selection criteria, such as treatment response measured by minimal residual disease, should be considered to address the issue of treatment reduction.
儿童标准风险（SR）急性淋巴细胞白血病（ALL）的治疗通常是成功的。然而，强化化疗方案可能会带来严重的治疗后遗症。因此，人们正在努力识别那些接受强度较低的治疗同样能成功但长期后遗症较少的患者。本研究的目的是评估在一组失败风险极小的ALL患儿中减少治疗强度的疗效。
SR ALL患者群体包括年龄在1至6岁、白细胞计数低于20,000/mm³、非T免疫表型、DNA指数在1.16至1.6之间、不存在t(9;22)和t(4;11)克隆性易位、无髓外白血病、对泼尼松反应良好且诱导治疗结束时达到完全缓解（CR）的儿童。采用了强度降低的BFM型治疗方案（AIEOP - ALL 9501方案）。诱导治疗仅基于长春新碱、泼尼松、L - 天冬酰胺酶和鞘内注射甲氨蝶呤；给予4次大剂量甲氨蝶呤（2 g/m²）。BFM方案II作为再诱导治疗；因此蒽环类药物的总剂量为120 mg/m²，未使用表鬼臼毒素或颅脑照射。
1995年5月至1999年12月期间，123例患者被确定为患有SR - ALL（占ALL - 95群体的7.8%），其中102例接受了SR方案。中位随访5.9年后，SR方案组中有11例患者复发，1例在缓解期死亡，1例发生了第二种恶性肿瘤。5年时的生存率和无事件生存率（EFS）概率（标准误）分别为97.0%（1.7）和86.7%（3.5），7年时分别为95.3%（2.4）和86.7%（3.5）。
尽管大多数复发患者得到了挽救，但在这一小群经过高度选择的患者中，长期EFS概率仍低于预期。因此，应考虑采用替代选择标准，如通过微小残留病测量的治疗反应，来解决治疗强度降低的问题。
