含硼替佐米的诱导化疗序贯自体造血干细胞移植治疗多发性骨髓瘤的疗效和安全性

The efficacy and safety of bortezomib-based induction regimen before autologous hematopoietic stem cell transplantation in patients with multiple myeloma

目的观察含硼替佐米的诱导化疗序贯自体造血干细胞移植（ASCT）治疗多发性骨髓瘤（MM）的疗效和安全性。方法回顾性分析2006年6月至2011年6月在中山大学附属第一医院接受含硼替佐米的方案诱导化疗序贯ASCT治疗的62例MM患者，所有患者均随访至2011年9月30日。结果含硼替佐米的诱导化疗总反应率（ORR）为88．7％，≥接近完全缓解（nCR）率为66．1％，完全缓解（CR）率为24．2％。患者在接受ASCT后，CR率升至50．0％，≥nCR率升至82．3％，同诱导后的疗效相比差异均有统计学意义（P=0．003和P=0．032）。移植后中性粒细胞重建时间、血小板重建时间分别为12．0（9～43）d、13．5（0～120）d。既往接受含烷化剂治疗患者的造血重建要慢于不含烷化剂治疗者，接受骨髓移植患者的造血重建慢于接受外周血干细胞移植患者。含硼替佐米诱导化疗期间及移植期间无预期外副作用发生。该组患者中位随访时间为26．5（7—61）个月，中位总生存期（OS）尚未达到，中位无进展生存期（PFS）为30个月。移植前疗效为CR／nCR患者组的OS和PFS均长于≤部分缓解（PR）患者组。结论含硼替佐米的诱导化疗可提高ASCT的疗效，应用过程安全。移植前高缓解质量与长OS和PFS相关。

Objective To investigate the efficacy and safety of bortezomib-based induction regimen followed by autologous hematopoietic stem cell transplantation （ASCT） in pationts with multiple myeloma （MM）. Methods A retrospective analysis was performed upon clinical data of 62 MM patients who received bortezomib-based induction regimen followed by ASCT from June 2006 to June 2011. All patients were followed up to September 30, 2011. Results Overall response rate [ complete remission （CR） ＋ near complete remission （nCR） ＋ partial remission （PR） ], /〉 nCR rate （CR/nCR） and CR rate of postinduction with bortezomib-based regimen were 88.7% , 66. 1% and 24. 2% , respectively. After ASCT, CR rate and CR/nCR rate were increased to 50. 0% and 82. 3% , respectively, with significant differences （P =0. 003 and P =0. 032）. The median time of neutrophil and platelet engraftment was 12. 0 （9-43） days and 13.5 （0-120） days, respectively. Significances were found in neutrophil and platelet engraftment between MM patients with and without prior exposure to alkylating agents. Furthermore, engraftment of neutrophil and platelet in patients receiving peripheral blood stem cell transplantation were faster than those receiving bone marrow transplantation. No unexpected side effects occurred. The median time of follow-up was 26. 5 （7-61） months. The median overall survival （OS） was not reached and the median progressionfree survival （PFS） was 30 months. There were significant differences in OS and PFS between patients obtaining CR/nCR and those with ≤ PR before ASCT. Conclusions Bortezomib-based induction regimen can improve the efficacy of ASCT in MM patients. The side effects are tolerant. Higher response quality before ASCT can translate to high rates of OS and PFS following high-dose therapy and stem cell transplantation.