Thiotepa, Busulfan, Cyclophosphamide: Effective but Toxic Conditioning Regimen Prior to Autologous Hematopoietic Stem Cell Transplantation in Central Nervous System Lymphoma.

Lebon Delphine, Debureaux Pierre-Edouard, Royer Bruno, Gruson Bérengère, Joris Magalie, Votte Patrick, Marolleau Jean-Pierre, Morel Pierre
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Abstract

In primary central nervous system lymphoma, two-year progression-free survival rates of up to 63 percent have been reported for first-line autologous stem cell transplantation after conditioning with the thiotepa busulfan cyclophosphamide regimen. However, 11 percent of the patients died due to toxicity. Besides conventional survival, progression-free survival and treatment related mortality analyses, a competing-risk analysis was applied to our cohort of twenty-four consecutive patients with primary or secondary central nervous system lymphoma who underwent autologous stem cell transplantation after thiotepa busulfan cyclophosphamide conditioning. The two-year overall survival and progression-free survival rates were 78 percent and 65 percent, respectively. The treatment-related mortality rate was 21 percent. The competing risks analysis demonstrate that age 60 or over and the infusion of less than 4.6 × 106/kg CD34+ stem cells were significant adverse prognostic factors for overall survival. Autologous stem cell transplantation with thiotepa busulfan cyclophosphamide conditioning was associated with sustained remission and survival. Nevertheless, the intensive thiotepa busulfan cyclophosphamide conditioning regimen was highly toxic, especially in older patients. Thus, our results suggest that future studies should aim at identifying the subgroup of patients who will really benefit of the procedure and/or to reduce the toxicity of future conditioning regimen.

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硫替帕、布苏凡、环磷酰胺:中枢神经系统淋巴瘤自体造血干细胞移植前有效但有毒性的调理方案。
在原发性中枢神经系统淋巴瘤中,经硫替帕-丁硫凡-环磷酰胺治疗后,一线自体干细胞移植的2年无进展生存率高达63%。然而,11%的患者因中毒而死亡。除了常规生存期、无进展生存期和治疗相关死亡率分析外,我们还对24例连续的原发性或继发性中枢神经系统淋巴瘤患者进行了竞争风险分析,这些患者在接受硫替帕-丁硫丹环磷酰胺治疗后接受了自体干细胞移植。两年总生存率和无进展生存率分别为78%和65%。与治疗相关的死亡率为21%。竞争风险分析表明,年龄60岁及以上和输注少于4.6 × 106/kg的CD34+干细胞是影响总生存的显著不良预后因素。自体干细胞移植与硫替帕-丁硫凡环磷酰胺调节与持续缓解和生存相关。然而,强化硫替帕-丁硫-环磷酰胺调理方案是高毒性的,特别是在老年患者中。因此,我们的研究结果表明,未来的研究应旨在确定真正受益于该手术的患者亚组和/或减少未来调理方案的毒性。
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