Nair A P, Walker P, Kalff A, Bergin K, Hocking J, Avery S, Curtis D J, Patil S, Das T, Klarica D, Morgan S, Muirhead J, Gorniak M, Reynolds J, Spencer A
Malignant Haematology, Alfred Hospital, Melbourne, Australia.
Australian Centre for Blood Diseases, Monash University, Melbourne, Australia.
Bone Marrow Transplant. 2017 Jun;52(6):839-845. doi: 10.1038/bmt.2017.37. Epub 2017 Mar 20.
High-risk (HR) multiple myeloma (MM) has poor outcomes with conventional therapy. Tandem autologous-non-myeloablative (NMA) allogeneic stem cell transplantation (autologous stem cell transplantation (ASCT)-NMA allogeneic SCT) is potentially curative secondary to graft-versus-myeloma effect. We retrospectively analysed ASCT-NMA allogeneic SCT outcomes of 59 HR and relapsed MM patients. At a median follow-up of 35.8 months, the outcomes for HR-MM upfront tandem ASCT-NMA allogeneic SCT and standard-risk (SR) MM upfront ASCT alone were comparable (median PFS 1166 days versus 1465 days, P=0.36; median overall survival (OS) not reached in both cohorts, P=0.31). The 5-year PFS and OS of patients who had ASCT-NMA allogeneic SCT after relapsing from previous ASCT were 30% and 48% respectively. High CD3+ cell dose (>3 × 10/kg) infusion was associated with more acute GvHD (grade 2-4) (47% vs 17.5%; P=0.03), extensive chronic GvHD (80% vs 50%; P=0.04), increased transplant-related mortality (26.3% vs 5%; P=0.009) and inferior OS (median OS 752 days vs not reached; P=0.002). On multivariate analysis, response achieved with tandem transplant (<CR vs CR vs stringent CR; hazard ratio=5.54, confidence interval=2.67-11.5; P<0.0001) and CD3+ cell dose infused (hazard ratio=1.42; confidence interval=1.21-1.67; P<0.0001) emerged as factors influencing OS. We conclude that tandem ASCT-NMA allogeneic SCT is an effective therapy for HR or relapsed MM and that higher CD3+ doses have an adverse impact on transplant outcome.
高危（HR）多发性骨髓瘤（MM）采用传统疗法预后较差。串联自体-非清髓性（NMA）异基因干细胞移植（自体干细胞移植（ASCT）-NMA异基因干细胞移植）因移植物抗骨髓瘤效应而具有潜在治愈性。我们回顾性分析了59例HR和复发MM患者的ASCT-NMA异基因干细胞移植结果。中位随访35.8个月时，HR-MM先行串联ASCT-NMA异基因干细胞移植与标准风险（SR）MM先行单纯ASCT的结果相当（中位无进展生存期[PFS]分别为1166天和1465天，P = 0.36；两个队列的中位总生存期[OS]均未达到，P = 0.31）。先前ASCT复发后接受ASCT-NMA异基因干细胞移植患者的5年PFS和OS分别为30%和48%。高剂量CD3+细胞输注（>3×10/kg）与更多的急性移植物抗宿主病（GvHD，2-4级）（47%对17.5%；P = 0.03）、广泛的慢性GvHD（80%对50%；P = 0.04）、移植相关死亡率增加（26.3%对5%；P = 0.009）以及较差的OS（中位OS 752天对未达到；P = 0.002）相关。多因素分析显示，串联移植取得的缓解情况（<完全缓解[CR]对CR对严格CR；风险比=5.54，置信区间=2.67-11.5；P<0.0001）和输注的CD3+细胞剂量（风险比=1.42；置信区间=1.21-1.67；P<0.0001）是影响OS的因素。我们得出结论，串联ASCT-NMA异基因干细胞移植是HR或复发MM的有效治疗方法，且较高的CD剂量对移植结果有不利影响。
