Hsi-Che Liu, Ting-Chi Yeh, Jen-Yin Hou, and Der-Cherng Liang, Mackay Medical College, New Taipei; and Hsi-Che Liu, Ting-Chi Yeh, Jen-Yin Hou, Kuan-Hao Chen, Ting-Huan Huang, Ching-Yi Chang, and Der-Cherng Liang, Mackay Memorial Hospital, Taipei, Taiwan.
J Clin Oncol. 2014 Jun 10;32(17):1825-9. doi: 10.1200/JCO.2013.54.5020. Epub 2014 May 12.
To eliminate the toxicities and sequelae of cranial irradiation (CrRT) and to minimize the adverse impact of traumatic lumbar puncture (TLP) with blasts, a prospective study of a modified CNS-directed therapy was conducted in children with acute lymphoblastic leukemia (ALL).
Since June 1999, children with newly diagnosed ALL have been treated with triple intrathecal therapy (TIT) alone without CrRT. The first TIT was delayed until the disappearance of blasts from peripheral blood (PB) for up to 10 days of multidrug induction, and CrRT was omitted in all patients. If PB blasts persisted on treatment day 10 (d10), the TIT was then performed.
Of a total of 156 patients, 152 were eligible. Seventeen patients did not have PB blasts at diagnosis. Three fourths of the remaining patients achieved complete clearance of PB blasts by d10. Only hyperleukocytosis at diagnosis showed a significantly lower clearance rate. Six standard-risk patients were upgraded to high risk because of detectable PB blasts on d10. TLPs were encountered in four patients (2.6%), but none were contaminated with lymphoblasts. Neither CNS-2 (less than 5 WBCs/μL with blasts in a nontraumatic sample) nor CNS-3 (≥5 WBCs/μL with blasts in a nontraumatic sample or the presence of cranial nerve palsy) was present. The 5-year event-free survival and overall survival rates±SE were 84.2%±3.0% and 90.6%±2.4%, respectively. No isolated CNS relapse occurred, but two patients experienced combined CNS relapses. The 7-year cumulative risk of any CNS relapse was 1.4%±1.0%.
Delaying first TIT until circulating blasts have cleared may improve CNS control in children with newly diagnosed ALL and preclude the need for CrRT.
消除颅脑照射（CrRT）的毒性和后遗症，最大限度地减少创伤性腰椎穿刺（TLP）与爆炸物的不良影响，对急性淋巴细胞白血病（ALL）患儿进行了一项改良的中枢神经系统定向治疗的前瞻性研究。
自 1999 年 6 月以来，新诊断为 ALL 的儿童仅接受三联鞘内治疗（TIT），而不进行 CrRT。第一次 TIT 延迟至多药诱导后外周血（PB）中 blast 消失，最多 10 天，如果 PB blasts 在治疗第 10 天（d10）仍然存在，则进行 TIT。
在总共 156 名患者中，有 152 名符合条件。17 名患者在诊断时没有 PB blast。其余患者中有四分之三在 d10 时完全清除 PB blast。只有初诊时的高白细胞计数显示清除率明显较低。由于 d10 时可检测到 PB blast，6 名标准风险患者升级为高危。4 名患者（2.6%）发生 TLP，但均未与淋巴细胞污染。无 CNS-2（非创伤性样本中未见 blast 的白细胞计数<5 个/μL）或 CNS-3（非创伤性样本中白细胞计数≥5 个/μL，或颅神经麻痹）。5 年无事件生存和总生存率±SE 分别为 84.2%±3.0%和 90.6%±2.4%。未发生孤立性 CNS 复发，但有 2 例患者发生联合 CNS 复发。任何 CNS 复发的 7 年累积风险为 1.4%±1.0%。
延迟第一次 TIT 直至循环 blast 清除，可能改善新诊断 ALL 患儿的中枢神经系统控制，并避免 CrRT 的需要。
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