High-dose thiotepa, busulfan, cyclophosphamide and ASCT without whole-brain radiotherapy for poor prognosis primary CNS lymphoma
High-dose thiotepa, busulfan, cyclophosphamide and ASCT without whole-brain radiotherapy for poor prognosis primary CNS lymphoma
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DOI：
10.1038/sj.bmt.1703917
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发表时间：
2003-04-01
影响因子：
4.8
通讯作者：
Stewart, DA
中科院分区：
文献类型：
--
作者：
Cheng, G;Forsyth, P;Stewart, DA
采用基于大剂量甲氨蝶呤 (HD-MTX) 的联合化疗和全脑放疗 (WBRT) 治疗原发性中枢神经系统淋巴瘤 (PCNSL) 与严重的神经毒性相关，但高复发率与单独使用任一方式相关。为了改善这些令人沮丧的结果，我们对 7 名 PCNSL 患者进行了基于 HD-MTX 的诱导治疗，随后接受噻替派、白消安、环磷酰胺 (TBC) 和自体干细胞移植 (ASCT)，但没有进行 WBRT。其中 6 名患者至少具有以下不良预后特征之一：卡诺夫斯基体能状态 (KPS) 小于或等于 50%、年龄 >60 岁或疾病复发。除一名患者外，所有患者都对治疗耐受良好，并且移植后神经功能和整体表现状态均得到改善。尽管随访时间较短，但未观察到治疗引起的神经毒性（痴呆、共济失调和失禁）。一名患有多种合并症的患者发生了一起早期治疗相关死亡。其他六名患者在 TBC 和 ASCT 后达到完全缓解 (CR)。 5 名患者目前还活着，并且在诊断后 5、8、24、36 和 42 个月时没有复发。另外一名患者在诊断后 33 个月复发并死亡。七名患者中的两名接受了 TBC/ASCT 作为初次化疗后疾病进展的唯一治疗方法，并且在本报告撰写时（即 TBC/ASCT 后 22 个月和 31 个月），两人均未复发。总之，预后不良的 PCNSL 经单纯化疗治疗后可以获得延长的 CR。此外，本系列文章建议 PCNSL 的高剂量化疗应包括渗透中枢神经系统的药物，如白消安和塞替派，而不是标准淋巴瘤治疗方案，如 BEAM。
Treatment of primary central nervous system lymphoma (PCNSL) with combined high-dose methotrexate (HD-MTX)-based chemotherapy and whole-brain radiotherapy (WBRT) is associated with severe neurotoxicity, but high relapse rates are associated with the use of either modality alone. In an attempt to improve upon these dismal results, we treated seven PCNSL patients with HD-MTX-based induction therapy followed by thiotepa, busulfan, cyclophosphamide (TBC), and autologous stem cell transplant (ASCT), without WBRT. Six of these patients had at least one of the following poor prognostic features: Karnofsky performance status (KPS) less than or equal to50%, age >60 years, or relapsed disease. All but one patient tolerated the treatment well and experienced improvements in neurological function and overall performance status posttransplant. No treatment-induced neurotoxicity (dementia, ataxia, and incontinence) was observed although the follow-up is short. One early treatment-related death occurred in a patient with multiple comorbid medical conditions. The other six patients achieved a complete response (CR) after TBC and ASCT. Five patients are currently alive and relapse-free at 5, 8, 24, 36, and 42 months from diagnosis. One additional patient relapsed and died 33 months after diagnosis. Two of the seven patients received TBC/ASCT as the only treatment after disease progression following their initial chemotherapy and both remain relapse-free at the time of this report, 22 and 31 months post-TBC/ASCT. In conclusion, prolonged CR can be attained after chemotherapy-only treatment of poor prognosis PCNSL. Furthermore, this small series suggests that high-dose chemotherapy for PCNSL should include drugs that penetrate the CNS such as busulfan and thiotepa rather than standard lymphoma regimens such as BEAM.