诱导治疗序贯自体外周血造血干细胞移植后201例多发性骨髓瘤患者的疗效及预后影响因素

Efficacy and prognostic factors of induction therapy combined with autologous stem cell transplantation in 201 patients with multiple myeloma

目的探讨诱导治疗序贯自体外周血造血干细胞移植（APBSCT）后多发性骨髓瘤（MM）患者预后的影响因素。方法回顾性分析1998年1月至2015年5月接受诱导治疗序贯APBSCT的201例MM患者临床资料。对预后影响因素进行分析。结果@201例患者中位疾病无进展生存（PFS）期为22．87（17．48～28．26）个月，中位总生存（OS）期为69．63（63．57-75．69）个月，5年PFS率、OS率分别为17％、49％。（~）APBSCT后达完全缓解（cR）组（112例）与未达CR组（89例）的中位PFS期分别为32．93（21．03～44．83）、18．13（14．46～21．80）个月（P〈0．001），中位OS期分别为96．77（71．79～121．75）、54．70（49．53～59．87）个月（P=0．004）。③诱导治疗方案含硼替佐米或沙利度胺组（123例）与不含硼替佐米或沙利度胺组（21例）的中位PFS期分别为31．67（24．36～38．98）、15．20（10．11-20．29）个月（P=0．013），中位OS期分别为76．30（55．44～97．15）、52．03（33．76～70．30）个月（P=0．014）。④国际分期系统（ISS）I、Ⅱ、Ⅲ期组中位OS期分别为99．47（59．58～139．36）、66．77（52．17～81．37）、53．97（28．71～79_23）个月（P〈0．001），Ⅱ、Ⅲ期患者发生死亡的风险分别为I期患者的2．16、3．40倍。⑤IgD型（22例）、IgG型（101例）MM患者中位PFS期分别为11．17（10．27～13．13）、35．43（22．69~48．17）个月（P=0．007），中位OS期分别为30．83（0．24～61．42）、70．70（53．52～87．88）个月（P=0．039），IgD型患者发生疾病进展的风险是IgG型患者的2．47倍。⑥接受一线诱导（132例）和更换诱导治疗方案（69例）患者的中位PFS期分别为25．43（16．09～34．77）、20．27（15．04～25．50）个月（P=-0．042），后者发生疾病进展的风险较前者高1．48倍，两组中位OS期差异无统计学意义（P=0．415）。⑦Cox多因素回归分析显示，移植后达CR和ISS分期是影响OS的独立预后因素，IgD型、移植后达CR是影响PFS的独立预后因素。结论移植后达CR、ISS分期是影响MM患者OS的独立预后因素。移植后达CR、IgD型也是影响PFS的独立预后因素。

Objective To explore the efficacy and prognostic factors of induction therapy combined with autogenetic peripheral blood stem cells transplantation （APBSCT） in patients with multiple myeloma （MM）. Methods From January 1998 to May 2015, 201 patients with MM were enrolled. All patients received APBSCT after induction therapy. With the follow up to 20 June 2015, the overall survival（OS）, progression free survival （PFS） and prognostic factor were analyzed. Results With a media follow up of 36.67 months, the median PFS and OS were 22.87 （17.48-28.26） and 69.63 （63.57-75.69） months, 5-year PFS and OS were 17% and 49%, respectively. After APBSCT, when the subgroup （n= 112） achieved complete response （CR） compared with the subgroup （n=89） not achieved CR, the median PFS were 32.93 （21.03-44.83） and 18.13 （14.46-21.80） months （P〈0.001）, respectively; And the media OS were 96.77 （71.79-121.75） and 54.70 （49.53-59.87） months （P=0.004）, respectively. The risks for disease progression and death declined in CR subgroup. Two subgroups included or not included bortezomib/thalidomide at induction therapy （123 patients vs 21 patients）, the media PFS were 31.67 （24.36-38.98） and 15.20（10.11-20.29） months （P=0.013）, respectively; And the media OS were 76.30 （55.44- 97.15） and 52.03 （33.76- 70.30） months （P=-0.014）, respectively. According to the ISS stage, the media OS of stage I、Ⅱ、Ⅲ were 99.47（59.58-139.36）, 66.77（52.17-81.37）, 53.97（28.71-79.23） （P〈 0.001 ）, respectively. The risk for death of stage Ⅱ、Ⅲ were 2.16 and 3.04 times higher than stage I, with no difference in terms of PFS. The media PFS in IgD （n=22） and IgG （n=101） type MM were 11.17 （10.27-13.13） and 35.43 （22.69-48.17） months （P=-0.007） , respectively; The media OS were 30.83 （0.24-61.42） and 70.70 （53.52-87.88） months （P=0.039）, respectively. The risk for disease progression of IgD type was 2.47 times higher than IgG type. @Patients received 1 line induction therapy （n=132） compared with more than 1 line （n=69）, the media PFS were 25.43 （16.09-34.77） and 20.27 （15.04- 25.50） months （P=0.042）. Cox analysis showed that CR after APBSCT and ISS stage were independent prognostic factors for OS. IgD type MM and CR after APBSCT were independent prognosis factor for PFS. Conclusion CR after APBSCT and ISS stage were independent prognostic factors for OS in MM. CR after APBSCT was independent prognostic factor for PFS in MM. However, disease progression more likely occurred in IgD type MM, which was independent negative prognostic factor for PFS in MM.