Barredo Julio C, Devidas Meenakshi, Lauer Stephen J, Billett Amy, Marymont Maryanne, Pullen Jeanette, Camitta Bruce, Winick Naomi, Carroll William, Ritchey A Kim
Department of Pediatrics, Medical University of South Carolina, Charleston, SC, USA.
J Clin Oncol. 2006 Jul 1;24(19):3142-9. doi: 10.1200/JCO.2005.03.3373.
Prognosis and outcome of children with isolated CNS relapse of acute lymphoblastic leukemia (ALL) has depended on duration of first complete remission (CR1). This study intensified systemic therapy by delaying CNS radiation for 12 months and tailored CNS radiation by CR1 duration.
Seventy-six children with first isolated CNS relapse of ALL were treated with systemic chemotherapy that effectively penetrates into the CSF and intrathecal chemotherapy for 12 months. Patients with CR1 of less than 18 months received craniospinal radiation (24 Gy cranial/15 Gy spinal), whereas those with CR1 of 18 months or more received cranial radiation only (18 Gy), followed by maintenance chemotherapy. Additionally, asymptomatic patients were enrolled in a thiotepa up-front therapeutic window.
Seventy-four (97.4%) of 76 eligible patients achieved a second remission. Overall 4-year event-free survival (EFS) for the 71 precursor B-cell patients was 70.1% +/- 5.8%. CR1 duration and National Cancer Institute (NCI; National Institutes of Health, Bethesda, MD) risk group at initial diagnosis predicted outcome. Patients with CR1 of less than 18 months and 18 months or more had a 4-year EFS of 51.6% +/- 11.3% and 77.7% +/- 6.4% (P = .027), respectively. NCI high- versus standard-risk 4-year EFS was 51.4% +/- 10.8% and 80.2% +/- 6.3% (P = .0018), respectively. A significant difference in EFS between standard risk/CR1 of at least 18 months and both high risk/CR1 of less than 18 months and high risk/CR1 of at least 18 months groups was detected (P = .0068 and .0314, respectively). Response rate to thiotepa was 78%. Most relapses involved the bone marrow, and three second malignancies were reported.
Twelve months of intensive systemic chemotherapy with reduced dose cranial radiation (18 Gy) is highly effective for children with isolated CNS relapse and CR1 of 18 months or more. Novel strategies are needed for patients with CR1 of less than 18 months.
急性淋巴细胞白血病（ALL）孤立性中枢神经系统复发患儿的预后和转归取决于首次完全缓解（CR1）期的时长。本研究通过将中枢神经系统放疗推迟12个月强化全身治疗，并根据CR1期时长调整中枢神经系统放疗方案。
76例首次发生ALL孤立性中枢神经系统复发的患儿接受了能有效穿透脑脊液的全身化疗及鞘内化疗，为期12个月。CR1期少于18个月的患者接受全脑脊髓放疗（颅脑24 Gy/脊髓15 Gy），而CR1期为18个月或更长时间的患者仅接受颅脑放疗（18 Gy），随后进行维持化疗。此外，无症状患者被纳入噻替派预先治疗窗。
76例符合条件的患者中有74例（97.4%）实现了第二次缓解。71例前体B细胞患者的4年无事件生存率（EFS）总体为70.1%±5.8%。CR1期时长及初始诊断时的美国国立癌症研究所（NCI；美国国立卫生研究院，马里兰州贝塞斯达）风险组可预测转归。CR1期少于18个月和18个月或更长时间的患者4年EFS分别为51.6%±11.3%和77.7%±6.4%（P = 0.027）。NCI高危组与标准风险组的4年EFS分别为51.4%±10.8%和80.2%±6.3%（P = 0.0018）。在标准风险/CR1期至少18个月组与高危/CR1期少于18个月组及高危/CR1期至少18个月组之间检测到EFS存在显著差异（分别为P = 0.0068和0.0314）。对噻替派治疗的缓解率为78%。大多数复发累及骨髓，报告了3例第二原发恶性肿瘤。
对于孤立性中枢神经系统复发且CR1期为18个月或更长时间的患儿，12个月的强化全身化疗联合降低剂量颅脑放疗（1）是非常有效的。对于CR1期少于18个月的患者，需要新的治疗策略。
