Retrospective Analysis On Multiple Myeloma Patients From Hematology Department Of The Second Hospital Of Hebei Medical University In The Past7Years

Objective: Make a retrospective analysis on the biological/clinicalcharacteristics, prognostic factor and treatment response of Multiple Myeloma(MM) patients from hematology department of the Second Hospital of HebeiMedical University in the past7years.Methods: On the basis of243cases of MM patients, including initialtreatment and retreatment cases, received and cured by the Second Hospital ofHebei Medical University from January2005to October2012, make aretrospective analysis on the clinical data, treatment response and survivalcondition of146initial treatment cases therein with integral information. UseSPSS18.0for statistical analysis, X±S for measurement data, analysis ofvariance for comparing differences of therapeutic efficacy,2examination forclinical characteristics of patients of different groups, Kaplan-Meier andLog-rank examination for survival analysis, and COX model for multivariateanalysis. MM diagnostic criteria, staging and typing as well as MM relatednephropathy diagnosis is subject to Standard of Diagnosis and TherapeuticEffect of Hematopathy.Results:1.Clinical data:①General information:146cases of MMpatients cover80males and66females (ratio1:20.1) with median age of59(26-78), in which7cases under40years (4.79%),24cases between the age of40and49(16.44%),44cases between50and59(30.14%),54cases between60and69(37.00%) and17cases over70years (11.63%).②O nset symptoms:commonly are fatigue and ostealgia, accounting for34.20%and27.40%respectively;17cases are of such urinary system symptoms as facial edema,both lower limbs edema and abnormalities in urine test, accounting for11.64%;9cases are of such digestive system symptoms as nausea and vomiting, poor appetite and abdominal pain and distension, accounting for6.16%;13cases of such infection symptoms as pyrexia, tussis andexpectoration, accounting for8.90%;9cases are of such hemorrhagesymptoms as epistaxis, gingival bleeding and menorrhagia, accounting for6.16%,other accounting for5.49%③C linical staging and typing: for146MMpatients,67cases are of IgG (45.89%),38cases are of IgA (26.03%),30casesare of light chain (20.55%),10cases of IgD (6.85%),1case is ofnon-secreting (0.68%), null case for IgE, IgM and biclone (0%). For clinicalstaging in accordance with International Standard for Staging (ISS),17casesare of stage I (11.64%),38cases are of stage II (26.03%) and91cases are ofstage III (62.33%).2.Laboratory examinations:(1) Blood Routine:128cases are of HGB＜110g/L (87.67%) with average level of80.86±20.96g/L;54.79%are ofmoderate anemia with HGB average level of78.25±8.10g/L; Hgb level ofpatients of stages II&III is significantly lower than that of patients of stage I,P=0.014.(2)Bone Marrow Smear: The average ratio of myeloma cell tokaryocyte for MM patients is38.57±23.88%（2.5-95%）, in which15caseshave the ratio less than15%(10.27%),136cases have the ratio more than10%(89.70%) and81cases have the ratio more than30%(55.50%).(3)Immunophenotypic Characteristics: Abnormal plasma cell isvisible, accounting for0.50%-66.00%of karyocyte (average level is15.62±14.49%); CD45is positive or weakly positive, CD38and138are stronglypositive, and CD19negative;63out of64patients have negative CD20(98.44%) and39out of64patients have positive CD56(60.94%); there is nostatistical significance on CD56expression for patients with differentimmunophenotype and staging (P=0.071and0.250respectively).(4)BloodBiochemical Item: The average level of ALB is33.13±7.74g/L,81cases<35g/L (55.48%) and65cases≥35g/L (44.52%); The average level of serumcreatinine (Cr) is180.67±152.63umol/L,48cases≥136umol/L (32.88%) and98cases<136umol/L(67.12%); The average level of β2-MG is8.16±5.91mg/L,27cases <3.5mg/L (18.49%),28cases between3.5-5.5mg/L (19.18%) and90cases≥5.5mg/L (62.33%); Immunoglobulin: IgG is71g/L(17.50-216g/L) and IgA34.40g/L (5.50-180g/L), usually accompanying with adecline of normal immunoglobulin.(5)Serum and ImmunofixationElectrophoresis: M-protein is found in serum of59patients viaimmunofixation electrophoresis,10cases have negative urine Bence-Joneprotein (16.95%) and49cases have positive urine Bence-Jone protein(83.05%) which includes18cases of light chain urine Bence-Jone protein(60.00%).3.MM Osteopathia and Hypercalcemia:146patients have undergoneimageological examination (X-ray, CT or whole-body bone imaging).91caseshave accompanied with bone changes, accounting for62.33%, in which,39cases are of IgG (42.86%),24cases are of IgA (26.37%),9cases are of IgD(9.89%) and19cases are of light chain (20.88%). However, there is nostatistical significance on bone change for patients with differentimmunophenotype and staging (P=0.243). The average blood calcium level of146cases is2.37±0.49mmol/L,22cases≥2.75mmol/L, accounting for14.40%, in which5cases are of IgG (22.73%),8cases are of IgA (36.36%),9cases are of IgD (40.91%) and null case is of light chain (0%). There isremarkable statistical significance on blood calcium for patients with differentimmunophenotype and staging, that is, the serum calcium of MM patients ofIgD type is significantly higher than that of other hypotype MM patients withP=0.000. In91MM patients with osteopathia,14cases have rising bloodcalcium, accounting for15.38%, and77cases have normal blood calcium,accounting for84.62%.4.MM Related Nephropathy:①At initial treatment,48MM patients haveserum creatinine (Cr)≥136umol/L, accounting for32.88%, and98patients<136umol/L, accounting for67.12%. Divide MM patients into2groups ofnormal/abnormal renal function in accordance with Cr level, and then make acomparison regarding to clinical data between the said2groups. For group ofabnormal renal function,30males (62.50%) and18females (37.50%) withmale/female ratio1.67:1; Onset age:3cases have onset age <40(6.25%),7 cases between40-49(14.58%),16cases between50-59(33.33%),18casesbetween60-69(37.50%) and4cases≥70(8.34%); Hgb level:18cases haveHgb≥80g/L (37.50%) and30cases<80g/L (62.50%); Uric acid (UA) level:18cases have normal UA (37.50%) and30cases have rising UA (62.50%); Bloodcalcium level:36cases have normal blood calcium (75.00%) and12caseshave rising blood calcium (25.00%); Clinical staging: null cases are of stage I(0%),4cases are of stage II (8.33%) and44cases are of stage III (91.67%);Clinical typing:21cases are of IgG (43.75%),5cases are of IgA (10.42%);3cases are of IgD (6.25%) and19cases are of light chain (39.58%). For groupof normal renal function,50males (51.02%) and48females (48.98%) withmale/female ratio1.04:1; Onset age:4cases have onset age <40(4.08%),17cases between40-49(17.35%),28cases between50-59(28.57%),36casesbetween60-69(36.73%) and13cases≥70(13.24%); Hgb level:53cases haveHgb≥80g/L (54.08%) and45cases<80g/L (45.92%); Uric acid (UA) level:77cases have normal UA (78.57%) and21cases have rising UA (21.43%); Bloodcalcium level:88cases have normal blood calcium (89.80%) and10caseshave rising blood calcium (10.20%); Clinical staging:17cases are of stage I(17.35%),34cases are of stage II (34.69%) and47cases are of stage III(47.96%); Clinical typing:46cases are of IgG (46.94%),33cases are of IgA(33.67%);7cases are of IgD (7.14%) and11cases are of light chain(11.22%),1cases are of non-secreting(1.03%).Via statistical analysis, themorbidity is distinctly higher in MM patients with abnormal renal functionand of male, anemia, hypercalcemia, hyperuricemia and of stage III than thatwith normal renal function (P=0.039,0.031,0.000,0.009,0.000,respectively).②V ia logistic regression analysis, renal damage on MMpatients has correlation withβ2-microglobulin level and blood calcium level,P=0.000and0.030; and that has no significant correlation with theimmunoglobulin type, number of myeloma cells, hemoglobin, platelet andalbumin levels, P=0.639,0.087,0.477,0.892and0.167.5.Treatment:①T herapeutic Regimen: VAD (vincristine, adriamycin/Pir-arubicin/epirubicin and dexamethasone); MP (melphalan and prednison); bortezomib and combined chemotherapy, and so forth.117cases undergoVAD treatment,7cases MP treatment,17cases bortezomib and combinedchemotherapy,5cases thalidomide treatment,6cases undergo plasmapheresis,5cases hematodialysis and2cases need to maintain long-termhemodialysis.②Therapeutic Response:77patients have completelyundergone4courses of treatment and can be evaluated on curative effects. For61cases receiving VAD treatment,38cases are effective with a response rateof62.30%; median time to achieve PR is4.20months and median time toprogression10months. For5cases receiving MP treatment,2cases areeffective,1case in stable and2cases have disease progression. For11casesreceiving bortezomib and combined chemotherapy,10cases are effective and1case has disease progression, with a response rate of90.90%; median time toachieve PR is2.90months and median time to progression12months. Thereis statistical significance for VAD regimen and bortezomib and combinedchemotherapy in the time achieving plateau phase with P=0.042, while nostatistical significance in the time to progression with P=0.618. The averagetime to achieve plateau phase for MM patients of types of IgG, IgA, lightchain and IgD is4.31±1.21months,3.99±1.05months,3.98±0.87months and5.00±1.05months respectively; median time to achieve plateau phase is3.90months,4.10months,4.30months and5.20months respectively; there is nostatistical significance in the time achieving therapeutic plateau for patients ofdifferent types, P=0.339.6.Survival Analysis:①Survival time: Overall survival (OS) of146MMpatients is20.46±15.60and median OS is19months (1-88months). Viasingle factor analysis, prognosis on MM patients has correlation with onsetage, total amount of myeloma cells, hemoglobin, albumin, serum creatinineand β2-microglobulin (P=0.004,0.022,0.002,0.048,0.000and0.022);While that has no correlation with gender, types, urea, uric acid and bloodcalcium levels (P=0.222,0.215,0.174,0.215and0.052). Via multivariateanalysis, OS has negative correlation with severe anemia and high serumcreatinine level (P=0.004and0.000).②Cause of Death:31patients died during the therapeutic process, in which15patients died of multiple organfailure (respiratory failure, circulatory failure and renal failure), accounting for48.39%;8died of infection (respiratory infection, septicemia and mixedinfection), accounting for25.81%;5died of intracranial hemorrhage,accounting for16.13%;1died of plasma cell leukemia, accounting for3.23%;2died of cardiovascular event, accounting for6.44%.Conclusion:1.Multiple Myeloma has a predilection on patients of agedover60and it affects more men than woman. Onset symptoms are mostlyweakness, anemia and ostealgia. Morbidity of type IgG is higher than otherhypotypes. Most patients are in stage III when they are admitted to hospital.2.Incidence of osteopathy for MM patients is62.33%, among themhypercalcemia is remarkably increased.3.Incidence of renal damage for MM patients is32.88%and renaldamage has correlation with β2-microglobulin and blood calcium levels,may be reciprocal causation.4.Compared with VAD regimen, bortezomib and combinedchemotherapy shortens the time to achieve therapeutic plateau, and fails toextend such plateau time.5.MM patients have quite different survival time. Via single factoranalysis, prognosis on MM patients has correlation with onset age, totalamount of myeloma cells, hemoglobin, albumin, serum creatinine and β2-microglobulin; Via multivariate analysis, severe anemia and high serumcreatinine level are independent adverse factors for MM patients.