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输注淋巴细胞剂量越高,淋巴细胞恢复情况越好,而这反过来又预示着多发性骨髓瘤患者自体造血干细胞移植后的总生存期更长。

Higher infused lymphocyte dose predicts higher lymphocyte recovery, which in turn, predicts superior overall survival following autologous hematopoietic stem cell transplantation for multiple myeloma.

作者信息

Hiwase Devendra K, Hiwase Smita, Bailey Michael, Bollard Geraldine, Schwarer Anthony P

机构信息

Haematology Department, Institute of Medical and Veterinary Science, Adelaide, South Australia, Australia.

出版信息

Biol Blood Marrow Transplant. 2008 Jan;14(1):116-24. doi: 10.1016/j.bbmt.2007.08.051.

Abstract

Autologous stem cell transplantation (ASCT) is the standard of care for patients with multiple myeloma (MM) younger than 70 years. However, despite this aggressive therapy most patients will still die of progressive disease. Recent reports have suggested that lymphocyte recovery is an important predictor of relapse or progressive disease in a number of hematologic malignancies including MM. We have conducted retrospective analysis of factors that could predict overall (OS) and progression free survival (PFS) in patients with MM who had ASCT. One hundred nineteen patients with multiple myeloma underwent ASCT. The median OS and PFS were 64 and 32 months, respectively. Univariate and multivariate analysis using Cox proportional hazards regression model showed that absolute lymphocyte count on day 30 following ASCT (ALC-30), international staging system (ISS) stage at diagnosis, and age at diagnosis significantly influenced OS and PFS following ASCT. OS (96 versus 48 months, P = .04) and PFS (43 versus 29 months, P = .03) following ASCT were higher in patients with ALC-30 >or=1.0 x 10(9)/L compared to patients ALC-30 <1.0 x 10(9)/L. Higher ALC-60, ALC-100, ALC-180, and ALC-365 did not predict superior OS and PFS. Patients with early-stage disease had significantly higher OS (ISS stages I, II, and III: 96, 53, and 29 months, respectively; P = .0023) and PFS (ISS stages I, II, and III: 55.5, 31, and 12 months, respectively; P = .027) compared to patients with advanced-stage disease at diagnosis. On univariate analysis, the type of initial chemotherapy (melphalan, VAD, PCAB), lymphocyte count on day of leukapheresis, and the lymphocyte dose infused (LY-DO) significantly influenced lymphocyte recovery following ASCT. Patients who received higher lymphocyte dose (LY-DO) >or=0.2 x 10(9)/kg had higher median ALC-15 (0.25 versus 0.19 x 10(9)/L; P = .3), ALC-30 (1.20 versus 0.99 x 10(9)/L; P = .08), ALC-60 (1.90 versus 1.01 x 10(9)/L; P = .013), ALC-100 (1.58 versus 1.03 x 10(9)/L; P = .016), and ALC-180 (1.33 versus 1.01 x 10(9)/L; P = .1), compared to patients who received LY-DO <0.2 x 10(9)/kg. In summary, our data suggest that infusing large numbers of lymphocytes improves lymphocyte recovery post-ASCT, and that higher ALC-30 is associated with better PFS and OS. These data suggest that a threshold number of CD34(+) cells should not be the only parameter considered for an adequate PBSC collection--perhaps a certain number of lymphocytes should be aimed for as well.

摘要

自体干细胞移植(ASCT)是70岁以下多发性骨髓瘤(MM)患者的标准治疗方法。然而,尽管采用了这种积极的治疗方法,大多数患者仍会死于疾病进展。最近的报告表明,淋巴细胞恢复是包括MM在内的多种血液系统恶性肿瘤复发或疾病进展的重要预测指标。我们对接受ASCT的MM患者中可预测总生存期(OS)和无进展生存期(PFS)的因素进行了回顾性分析。119例多发性骨髓瘤患者接受了ASCT。中位OS和PFS分别为64个月和32个月。使用Cox比例风险回归模型进行的单因素和多因素分析表明,ASCT后第30天的绝对淋巴细胞计数(ALC-30)、诊断时的国际分期系统(ISS)分期以及诊断时的年龄对ASCT后的OS和PFS有显著影响。与ALC-30<1.0×10⁹/L的患者相比,ALC-30≥1.0×10⁹/L的患者ASCT后的OS(96个月对48个月,P = 0.04)和PFS(43个月对29个月,P = 0.03)更高。较高的ALC-60、ALC-100、ALC-180和ALC-365并不能预测更好的OS和PFS。诊断时处于早期疾病的患者与晚期疾病患者相比,OS(ISS I、II和III期分别为96、53和29个月;P = 0.0023)和PFS(ISS I、II和III期分别为55.5、31和12个月;P = 0.027)显著更高。单因素分析显示,初始化疗类型(美法仑、VAD、PCAB)、白细胞分离术当天的淋巴细胞计数以及输注的淋巴细胞剂量(LY-DO)对ASCT后的淋巴细胞恢复有显著影响。与接受LY-DO<0.2×10⁹/kg的患者相比,接受较高淋巴细胞剂量(LY-DO)≥0.2×10⁹/kg的患者中位ALC-15(0.25×10⁹/L对0.19×10⁹/L;P = 0.3)、ALC-30(1.20×10⁹/L对0.99×10⁹/L;P = 0.08)、ALC-60(1.90×10⁹/L对1.01×10⁹/L;P = 0.013)、ALC-100(1.58×10⁹/L对1.03×10⁹/L;P = 0.016)和ALC-180(1.33×10⁹/L对1.01×10⁹/L;P = 0.1)更高。总之,我们的数据表明,输注大量淋巴细胞可改善ASCT后的淋巴细胞恢复,且较高的ALC-30与更好的PFS和OS相关。这些数据表明,CD34⁺细胞的阈值数量不应是评估足够的外周血干细胞采集的唯一参数——也许还应设定一定数量的淋巴细胞目标。

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