Division of Hematology, Mayo Clinic, Rochester, Minnesota.
Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota.
Am J Hematol. 2018 Jan;93(1):17-22. doi: 10.1002/ajh.24919. Epub 2017 Oct 20.
Achievement of a normal FLC ratio (FLCr) following treatment indicates hematologic response and suggests better outcomes in light chain amyloidosis (AL). We examined if elevated involved free light chain (hiFLC) impacts outcomes in patients achieving normal FLCr. We retrospectively analyzed 345 AL patients who were diagnosed within a 10-year period (2006-2015) and had 2 consecutive normal FLCr values after 1st line treatment. Among these, patients with hiFLC at 1 reading of normal FLCr (hiFLC1; n = 166; 48.1%) were compared to those who did not (n = 179; 51.9%). Patients with AL who have hiFLC1 after initial therapy had higher rates of multi-organ involvement (63.3 vs 46.4%; P = .002) and patients in advanced Mayo stage (42.9 vs 32.2%; P = .04) at diagnosis. The median progression free survival [PFS; 38.2 (95%CI; 26.4, 55.4) vs 67.1 (95%CI; 55.8, 88) months; P = .0002] and overall survival [OS; 94.4 (95%CI; 78, 107.1) vs not reached (NR, 95%CI; 116.1, NR) months; P < .0001] were lower in those who had hiFLC1. A more stringent comparison for patients with 2 consecutive hiFLC (hIFLC2; n = 111; 32.2%) versus not (n = 2234; 67.8%) showed consistent results [PFS; 27.1 (95%CI; 23, 53.8) vs 63.3 (95%CI; 55.4, 77) months; P < .0001 and OS; 78 (95% CI; 54.6, 98.8) vs NR (95%CI; NR, NR); P < .0001]. This poor prognostic impact of hiFLC on survival was independent of serum creatinine, Mayo stage, negative immunofixation status and inclusion of transplant in initial therapy on multivariate analysis. Hence, persistent elevation of iFLC predicts poor prognosis even among patients achieving normal ratio after initial therapy in AL.
在接受治疗后达到正常游离轻链比（FLCr）表明血液学反应，并提示轻链淀粉样变性（AL）的预后更好。我们研究了在达到正常 FLCr 的患者中，升高的游离轻链（hiFLC）是否会影响结局。我们回顾性分析了 345 名在 10 年内（2006-2015 年）诊断为 AL 的患者，这些患者在一线治疗后有 2 次连续的正常 FLCr 值。在这些患者中，与未达到正常 FLCr 值的患者（n=179，51.9%）相比，在第 1 次正常 FLCr 值时存在 hiFLC（hiFLC1；n=166，48.1%）的患者。初始治疗后 AL 患者的多器官受累率较高（63.3% vs 46.4%；P=0.002），晚期 Mayo 分期患者（42.9% vs 32.2%；P=0.04）。无进展生存期（PFS；38.2（95%CI；26.4，55.4）vs 67.1（95%CI；55.8，88）个月；P=0.0002）和总生存期（OS；94.4（95%CI；78，107.1）vs 未达到（NR，95%CI；116.1，NR）个月；P<0.0001）在存在 hiFLC1 的患者中较低。对于连续 2 次 hiFLC（hIFLC2；n=111，32.2%）和未达到 hiFLC（n=2234，67.8%）的患者进行更严格的比较，结果一致[PFS；27.1（95%CI；23，53.8）vs 63.3（95%CI；55.4，77）个月；P<0.0001和 OS；78（95%CI；54.6，98.8）vs NR（95%CI；NR，NR）；P<0.0001]。在多变量分析中，血清肌酐、Mayo 分期、阴性免疫固定电泳状态和移植纳入初始治疗后，hiFLC 对生存的不良预后影响独立于这些因素。因此，在 AL 患者中，即使在初始治疗后达到正常比值，游离轻链的持续升高也预示着预后不良。
