血清游离轻链κ/λ率在初诊多发性骨髓瘤患者诊断和预后中的作用

The roles of serum free light chain ratio in the diagnosis and prognosis of newly diagnosed multiple myeloma

目的分析血清游离轻链（sFLC）κ/λ比率（sFLCR）在初诊多发性骨髓瘤（MM）患者诊断和预后中的作用。方法回顾性分析2012年9月至2015年7月收治的82例初诊MM患者的临床资料，采用血清蛋白电泳（SPE）和免疫固定电泳（IFE）法检测血清单克隆蛋白（M蛋白）的表达，采用免疫比浊法检测sFLCκ、λ的表达水平，分析初诊时sFLCR在MM患者诊断和预后中的作用。结果初诊时82例患者中SPE法检测M蛋白阳性率为85．5％，IFE法检测M蛋白阳性率为93．9％，sFLC异常以及sFLCR异常者占96．3％。初诊时高比率组（sFLCR≥100或≤0．01，42例）与低比率组（0．01〈sFLCR〈100，40例）患者40个月的总生存率分别为87％和61％，差异有统计学意义（P=0．034）。与低比率组患者比较，高比率组患者初诊时血肌酐值、浆细胞数、B：微球蛋白增高，血红蛋白降低，肾功能不全及需要透析者、DS分期Ⅲ期B组者、ISS分期Ⅲ期者、FISH检查异常者、λ轻链异常者较多，κ轻链异常者较少（P值均〈0．05）。两组患者经过3-4个疗程诱导治疗后，高比率组和低比率组患者的治疗有效率（非常好的部分缓解及其以上）差异有统计学意义（45．2％对72．5％，P=0．012）。初诊肾功能不全者（肌酐≥178lumol／L，14例）与肾功能正常者（68例）的2年总生存率差异无统计学意义（85．7％对91．2％，P=0．894）。结论初诊时sFLC的检测相对于SPE和IFE法检测M蛋白对诊断MM有更高的敏感性；初诊时sFLCR明显异常的患者可能具有更高的肿瘤负荷和更强的侵袭性，可提示患者预后不良；初诊时伴有肾功能不全的MM患者经积极治疗后可获得与肾功能正常患者同样的疗效。

Objective The roles of serum free light chain ratio （sFLCR） in the diagnosis and prognosis of newly diagnosed multiple myeloma （NDMM） patients were analyzed. Methods The clinical data was retrospectively analyzed for 82 newly diagnosed multiple myeloma （NDMM） patients in the first affiliated hospital of Soochow University from September 28, 2012 to July 18, 2105. The serum free light chain levels were measured and κ/λ ratios were calculated, so we could analyze the roles of sFLCR in the diagnosis and prognosis of newly diagnosed multiple myeloma （NDMM） patients. Results It was 85.5% （70/82） positive of M protein by serum protein electrophoresis （SFE） and 93.9% （77/82） by serum immunofixation electrophoresis （IFE）. Both sFLC and sFLCR abnormalities were 96.3% （79/82）. The estimated 40-months overall survival was 87% for the high free light chain ratio group （sFLCR ≥100 or≤0.01） and 61% for the low free light chain ratio group （0.01〈sFLCR〈100）, respectively, with a statistical significance （P=-0.034）. Compared with low sFLCR group, high sFLCR group had elevated levels of serum creatinine, bone marrow plasma cells and 132-MG; lower level of hemoglobin; higher proportion of patients with renal dysfunction and selecting hemodialysis; more patients with DS stage ⅢB and ISS stage Ⅲ higher proportion of abnormal fluorescence in situ hybridization （FISH） and X chain isotype. The low risk group had a rise of n chain isotype （all P〈0.05）. And the difference was not statistically significant when compared with the age, sex, TP, ALB, CRP, LDH, Ca2＋, M protein and chromosome. After 3-4 courses of induction chemotherapy, based on the response criteria formulated by the IMWG for patients who could reach the Very Good Remission or better （VGPR＋）, the responses of VGPR＋ were 45.2% （19/42） in high sFLCR group and 72.5% （29/40） in low group （P=0.012）. Among them, there were 14 cases （17.1%） of NDMM with renal dysfunction. The 2-year survivals in patients with renal insufficiency and normal renal function were 85.7% and 91.2% （P=0.894）, respectively. Conclusion sFLC assay is much more sensitive than the common methods used, such as SPE and IFE for the diagnosis of MM. The patients with significantly abnormal sFLCR have more tumor burden, higher aggressive progression, and adverse prognosis. Compared with the patients who have normal renal function, the patients with renal insufficiency acquire the same effect after receiving reasonable treatment actively.