Conter V, Aricò M, Valsecchi M G, Rizzari C, Testi A, Miniero R, Di Tullio M T, Lo Nigro L, Pession A, Rondelli R, Messina C, Santoro N, Mori P G, De Rossi G, Tamaro P, Silvestri D, Biondi A, Basso G, Masera G
Clinica Pediatrica dell'Università di: Milano, Ospedale S. Gerardo, Monza, Italy.
Haematologica. 1998 Sep;83(9):791-9.
Since 1988 the AIEOP has used BFM-based chemotherapy for childhood ALL. Current organization and results and role of cranial irradiation in the AIEOP-ALL 91 study are reported.
From 1991 to 1995, 1194 children (< 15 years) with non-B ALL, were enrolled and assigned to the standard risk [SR: age > 1 year, non-T-ALL, BFM risk factor (RF) < 0.8], intermediate risk (IR: RF > or = 0.8 but < 1.7, or with RF < 0.8 and age < 1 year, or T-ALL), or high risk [HR: RF > or = 1.7, or t(9;22), or t(4;11) or prednisone poor response or late response or CNS involvement] groups. All patients received initially protocol Ia. Thereafter SR patients received HD-MTX 2 g/m2, a modified protocol II, and continuation therapy with triple intrathecal chemotherapy (TIT); IR patients received protocol Ib, HD-MTX 5 g/m2, protocol II and continuation therapy with TIT; HR patients received 9 polychemotherapy blocks, cranial irradiation and continuation therapy. Duration of treatment was 24 months. A randomized study was conducted to evaluate the impact of high-dose asparaginase in non high risk patients: the results of this study cannot be disclosed yet.
One thousand one hundred and fifty-two (96.5%) patients achieved CR. Overall EFS (SE) at 5-years was 71.0% (1.4), with a survival of 80.3% (1.3). Relapse occurred in 262 children (21.9%), either in the marrow (n = 192 isolated and 32 with other sites, 18.7%), in the CNS (n = 18, 1.5%), or elsewhere (n = 20, 1.7%). 5-year EFS (SE) was 83.3% (2.4) in SR, 74.7% (1.8) in IR, and 39.7% (3.5) in HR groups, respectively.
Overall cure rate was higher than in the previous AIEOP-ALL 88 study. Treatment intensification with polychemotherapy blocks did not improve results in HR. Cranial irradiation can be safely omitted in over 80% of children treated with BFM based chemotherapy.
自1988年以来，意大利儿童血液肿瘤协作组（AIEOP）一直采用基于柏林-法兰克福-明斯特（BFM）方案的化疗治疗儿童急性淋巴细胞白血病（ALL）。本文报告了AIEOP-ALL 91研究中的当前组织情况、结果以及颅脑照射的作用。
1991年至1995年，1194名15岁以下的非B系ALL患儿入组，并被分配至标准风险组[SR：年龄>1岁，非T系ALL，BFM风险因素（RF）<0.8]、中危组（IR：RF≥0.8但<1.7，或RF<0.8且年龄<1岁，或T系ALL）或高危组[HR：RF≥1.7，或t(9;22)，或t(4;11)，或泼尼松反应不佳或延迟反应或中枢神经系统受累]。所有患者最初均接受方案Ia治疗。此后，SR组患者接受2 g/m²的大剂量甲氨蝶呤（HD-MTX）、改良的方案II以及三联鞘内化疗（TIT）维持治疗；IR组患者接受方案Ib、5 g/m²的HD-MTX、方案II以及TIT维持治疗；HR组患者接受9个多药化疗疗程、颅脑照射以及维持治疗。治疗疗程为24个月。进行了一项随机研究以评估大剂量天冬酰胺酶对非高危患者的影响：该研究结果尚未公布。
1152名（96.5%）患者达到完全缓解（CR）。5年时的总体无事件生存率（EFS）（标准误）为71.0%（1.4），生存率为80.3%（1.3）。262名儿童（21.9%）出现复发，其中骨髓复发（n = 192例孤立性复发和32例伴有其他部位复发，18.7%）、中枢神经系统复发（n = 18例，1.5%）或其他部位复发（n = 20例，1.7%）。SR组、IR组和HR组的5年EFS（标准误）分别为83.3%（2.4）、74.7%（1.8）和39.7%（3.5）。
总体治愈率高于之前的AIEOP-ALL 88研究。多药化疗疗程强化治疗并未改善高危组的治疗结果。在接受基于BFM方案化疗的儿童中，超过80%的患儿可安全地省略颅脑照射。
