The Significances Of Serum Free Light Chains (sFLCs) Measurement In Multiple Myeloma

Backgrounds:Over the last few years a new immunoassays have emerged that allow the measurement of serum free immunoglobulin light chains(sFLCs) and provide a much greater sensitivity and convenience than older methods.As a quantative measurement,it had many clinical utilities in some immunogolubin elvating diseases,such as:multiple myeloma(MM),monoclonal gammopathy of undetermined significance(MGUS),AL amyloid,and so on.It is helpful in disease diagnosis,correlating with disease activity and prognosis,advance in monitoring disease progression,and helpful in early indication of treatment responses.However,there are no normal ranges and reference intervals for Chinese people and there is few study focused on MM patients from China.So the purposes of our study are:l.to estabilish normal ranges and reference intervals of sFLCs for Chinese people;2.to evaluate the clinical significances of sFLCs in MM patients from China.Methods:We used 104 healthy donors' frozen sera to detect sFLCs and calculated the normal ranges and reference intervals of sFLC-κ,sFLC-λ.and rFLC;we measured sFLCs concentrations of frozen sera samples from 122 newly diagnosed MM patients and analyzed their correlations with some other clinical parameters,and evaluated their significances in MM patients'diagnosis and prognosis,in addition,we traced 41 and measured their sFLCs levels to investigate the significances of sFLCs in early judgement of treatment efficy and disease monitoring.Results:1.We established the normal ranges and reference intervals of Chinese healthy people as below:κ9.82-27.80mg/L,λ12.2-33.73mg/L;rFLC 0.27-1.35;2.In 122 MM patients,we noticed that 121 patients(99.2%) were detected with abnormal sFLCs(contained the abnormalities of sFLCs concentrations and/or rFLC) and it was much more sensitive than immunofixation electrophoresis(89.3%in serum and 81.8%in urine) and serum protein electrophoresis(81.9%);3.The sFLCs concentrations were much higher in IgA MMand light chain MM than IgG MM patients(IgA-κ307mg/L vs LCMM-κ180mg/L vs IgG-κl54mg/L;IgA-λ774mg/L vs LCMM-λ1480mg/L vs IgG-λ482mg/L);4.The sFLCs concentrations were correlated with the percent of plasma cells in bone marrow,hemoglobin level,platelets,LDH,β2 microglobulin and CRP,but not with globulin and total light chains;5.The sFLCs concentratons and rFLC were both associated with patients survival and introducing Bortezomib could not eliminate this correlation,the ISS prognostic potential could be improved with the addition of rFLC;6.In 41 patients who were mornitored their sFLCs concentrations for at least 2 treatment courses,and we found in the seventh day of the first course,sFLCs levels and the ratio of changes of sFLCs concentrations and sFLCs at baseline were both associated with the optimal remission level,in addition,whether the rFLC was normal or not at the end of the first or second course also had the similar significance;7.Patients with normal rFLC at the end of first or second course had a trend of superior survival,but not achieving statistical significance.Conclusions:1.The normal ranges and reference intervals of sFLCs concentrations in our country were higher than western countries,while the rFLC was close to the reports from western countries;2.The measurement of sFLCs was sensivitive in MM diagnosis,and the baseline sFLCs and rFLC was associated with prognosis of patients and the ISS prognostic potential could be improved with the addition of rFLC;3.Because of the short half-life of sFLCs,it could provide a more rapid indication of the response to treatment and some suggestions for our treatment adjustments. Objectives:To explore the efficiency of chemotherapy,autologous or allogeneic stem cell transplantation in adults with non-Philadelphia chromosome-positive acute lymphoblastic leukemia(ALL) and investigate their relevant prognostic factors.Methods:The eligible ALL patients from January 2000 to December 2007 enter onto the study.Our protocols were designed as follows:induction therapy was a standard 4 or 5-drug regimen for 28 days,including:vincristine,doxorubicin,cyclophosphamide and prednisone,with or without L-asparaginase.The patients achieved complete remission (CR) after induction course would enter the next grouping:the patients,aged 15-45 years, who had suitable donors and transplantation will were assigned to allogeneic stem-cell transplantation(Allo-SCT),and for the rest,they would be assigned to accept chemotherapy(CT) or autologous stem-cell transplantation(ASCT) randomly.CT and ASCT group both received early intensification and consolidation therapy orderly,which contained high-dose methotrexate(HD-MTX),intermediate/high-dose cytarabine (I/HD-AraC) and high-dose or high-fraction cyclophosphamide,followed by ASCT or re-induction,later consolidation and maintenance chemotherapy for CT group.The patients in ASCT group would receive immunotherapy or maintenance chemotherapy for 1 year after ASCT.Here,we compared the disease-free survival(DFS),overall survival (OS) and relapse rate(RR) among the groups.Results:1.A total of 141 patients(age≥15 years) entered onto the trial and there were 94 males and 47 females,with a median age of 22 years(range:15-64 years).Median white blood cell(WBC) count at diagnosis was 8.96×10~9/L(range:0.7-320×10~9/L).2.After induction therapy,129 patients(93.2%) achieved CR and 3 patients died from the toxicity of induction treatment,because of 13 patients retreating from the trial,there were 116 patients entered the next grouping:22 in Allo-SCT group,48 in ASCT group and 40 in CT group.3.Actually,22 completed the Allo-SCT,44 completed ASCT(3 patients for early relapse and 1 for failing in collecting sufficient stem cells,and then all of them transferred to the CT group) and 50 received CT only.4.Follow-up and survival:After a median follow-up of 22 months(range:6-100 months), the median DFS time and OS time were 22 months and 25 months,respectively.The estimated 3-year DFS and OS were 45.6%±5.1%and 47.8±5.1%,respectively.[1]Allo-SCT group:According to the sources of stem cells,there were 16 patients accomplished sibling-HLA-compatible SCT,two patients accepted unrelated-HLA-compatible SCT,three patients accomplished haploid-compatible SCT and 1 received umbilical cord blood SCT.The median duration from CR to transplantation was 143 days(range:60-247 days) and the median follow-up was 20.5 months(range:6-101 months).Five patients(22.7%) died from transplant-related mortality(TRM) and 3 patients(13.6%) relapsed,both of the median DFS time and OS time were not achieved.The estimated 3-year DFS and OS were 57.0±11.1%and 55.8±11.4%,respectively.The 3-year accumulative RR was 16.2±8.7%.[2]ASCT group:The median duration from CR to ASCT was 173 days(range:108-330 days) and the median follow-up of 25.5 months(range:8-87 months).Four patients (9.1%) died from TRM and 11(25%) relapsed.Both of the median DFS time and OS time were also not achieved.The estimated 3-year DFS and OS were 55.1±8.5%and 55.2±8.5%,respectively.The 3-year accumulative RR was 31.8±8.2%.[3]CT group:After a median follow-up of 21 months(range:6-85 months),one patient (2.0%) expired during the consolidation course and 28 patients(56%) relapsed.The median DFS time and OS time were 19 months(95%CI:11.12-26.88 months) and 22 months(95%CI:14.99-29.01 months) The estimated 3-year DFS and OS were 33.7±7.5%和33.8±7.4%,respectively.The 3-year accumulative RR was 65.6±7.7%.[4]Comparasion:The DFS and OS of ASCT group were significantly superior to those of CT group(P=0.015 and 0.039,respectively),whereas the RR of CT group was much higher than that of ASCT group(P=0.001).The survival of patients in Allo-SCT group was also superior to that of patients in CT group,but it was not achieved statistical significance.There was no difference in survival between ASCT group and Allo-SCT group,but with a higher RR in ASCT group.5.The prognostic factors analysis indicated that the time-to-CR achievement>5 weeks was the unfavorable factor in all three subgroups.Conclusion:Adults with non-Philadelphia chromosome-positive ALL could achieve a satisfactory CR rate after accomplished the standard induction therapy,but the duration of CR and OS were short only with chemotherapy.SCT could improve the outcome of adult ALL patients,and because of high TRM and the limit of the source of donors in Allo-SCT, ASCT was an advisable choice after achieving CR for no-donors patients.