An Relapse Of Multiple Myeloma Predominantly Manifesting As Light Chain Escape: Laboratory Diagnosis And Its Clinical Value

ObjectiveAfter remission of treatment in patients with multiple myeloma（MM）,only Bence protein（BJP）levels increased during relapse,but there was no corresponding increase in M-protein（Monoclonal immunoglobulin,MIg）,This phenomenon is called Light Chain Escape（LCE）.In this study,we retrospectively analyzed the laboratory data of 30 cases of MM patients with LCE in our hospital from January 2011 to December 2017,systematically analyzed the laboratory performance of LCE,and explored the methods of early diagnosis of LCE and clinical value.Methods1.Case data collection 30 cases of MM patients with LCE in our hospital from January 2011 to December 2017 were tested and clinical data,with 30 cases of gender,M protein type,stage（D-S stage）and treatment in the same period.The MM patients with the same protocol who did not have LCE were used as the control group.The criteria for diagnosis,treatment,and recurrence of LCE in the enrolled patients were based on the"Guideline for the Diagnosis and Treatment of Chinese MM"revised in 2015;2.Experimental methods:1)Use serum protein electrophoresis and serum immunoelectrophoresis to identify MM;2)Determine the molecular M protein,urinary BJP,and serum free light chain（sFLC）levels by immunoturbidimetry;3)Analyze bone marrow by bone marrow biopsy Tumor cell ratio and morphology;4)Fully automatic biochemical analyzer detects serum total protein（TP）,albumin（Alb）,creatinine（Cr）,β₂-microglobulin（β₂-MG）,C-reactive protein（CRP）,lactate LDH and serum calcium（Ca）and other indicators;5)Hemoglobin（Hb）detected by automatic hematology analyzer;6)Medical laboratory of myeloma cells genetically approved by China National University of Health Sciences,Kang Shengda Medical Examination Center and other countries Testing.The above experimental results were analyzed to compare the experimental indicators of LCE and control patients at the time of initial diagnosis of MM and before and after LCE;the changes of sFLC and BJP during the course of LCE were analyzed;In combination with the patient’s clinical data,to explore the relevant laboratory diagnostic indicators and clinical value of LCE.Results1.At the time of initial diagnosis,there was no significant difference between the LCE group and the control group MM patients:serum,urinary protein electrophoresis and immunofixation electrophoresis.2.Serum TP,Alb,Cr,β₂-MG,CRP,LDH,Ca,Hb,bone marrow plasma cell ratio and genetics of myeloma cells showed no significant difference between the two groups,but the positive rate of BJP in LCE group was 76.7%（23/30）,significantly higher than the control group 23.3%（7/30）（χ²=11.38,P=0.001）,the sFLC level of the LCE group was significantly higher than the control group（t=2.360,P=0.036;t=2.281,P=0.043;t=3.434,P=0.026）;3.Comparison of MM before and after LCE:After LCE occurred,patients’M protein levels and Hb levels decreased significantly（t=7.753,P=0.000;t=4.313,P=0.000）;BJP,Cr,β₂-MG and sFLC The levels were significantly higher（t=-5.545,P=0.000;t=-4.256,P=0.000;t=-2.308,P=0.028;t=-4.48,P=0.000）,and there was no statistical difference in Alb,Ca levels（t=-0.987,P=0.332;t=-1.232;P=0.228）;Myeloma plasma cell morphology showed significant atypia;4.Comparison of changes in s FLC and BJP during the course of LCE:Abnormal changes in sFLC occurred approximately 71.5 days（ra-nge from 45 to 120 days）before LCE,and LCE was associated with severe renal insufficiency（renal failure or uremia）.At the time of the disease,the BJP level no longer rises or even declines during the course of disease,but the change of sFLC level is basically consistent with the condition of LCE patients;5.When LCE occurred,clinical symptoms such as anemia and bone pain were aggravated.The highest response level was VGPR,and 70.0% of patients died of infection or renal insufficiency.The survival analysis showed that the median survival time was between LCE and control groups.At 34 months and 57 months,Log-rank test was performed on the survival rates of the two groups.There was significant difference（χ²=10.668,P=0.001）.The prognosis of LCE group was worse than that of the control group.Conclusion1.Serum（urine）protein electrophoretograms,biochemical markers,b one marrow cytology,and myeloma cytogenetics at the time of MM initial diagnosis cannot predict the occurrence of LCE;2.MM patients with positive M protein at the time of initial diagnosis and with significantly elevated levels of BJP and sFLC must be vigilant to develop LCE;3.Dynamic monitoring of the whole molecule M protein,sFLC or BJP can be used to diagnose LCE;4.BJP can not truly reflect the condition of LCE patients with severe renal impairment,But the sFLC level is basically consistent with the patient’s condition,and helps to early detection of LCE,suggesting that monitoring sFLC during the course of LCE is more valuable than BJP;In addition,serum Cr,β₂-MG,Hb and myeloma plasma cell morphology can be used to assist in the diagnosis of LCE;The prognosis of MM patients After LCEis often poor,their survival period is significantly shortened,infection and renal insuffiency are the main causes of death.