The Clinical Observation Of Multiple Myeloma Treated With BD Regimen And VAD Regimen

ForewordMultiple myeloma is a hematopoietic malignancy, which is characterized by the hyperplasia of monoclonal plasma cell in bone marrow. It accounts for approximately10%of all hematologic malignancies. It happens in the elderly prone mostly, with a median age about65years old, male to female ratio is approximately3:2. In China, about14,000patients are newly diagnosed as multiple myeloma every year. The median survival time of untreated patients with multiple myeloma is six months to twelve months.Multiple myeloma has no good curative effect because of old age, low complete remission, high drug resistance, and high recurrence rate. Large dose chemotherapy combined with auto-HSCT can improve complete remission, but multiple myeloma is easy to recurrence, so it cann’t cue MM basically. Allo-HSCT may cure multiple myeloma in theory, but it is limited in clinical because of old age, significant organ insufficiency, and high transplant-related morality. The treatment goal of most MM patients is to prolong life, and improve the quality of life. Chemotherapy is the most basic and common choice, which can significantly improve survival time. Now, Combination chemotherapy is the most used treatment. VAD regimen is widely used, because the continuous intravenous injection of vincrinstine and doxorubicin can kill more tumor cells, but it can’t sharply improve the remission rate of MM or prolong survival.With clinical application of bortezomib and other new drugs, there is a rapid development in the treatment of multiple myeloma. Bortezomib is an ubiquitin-proteasome inhibitor, and the combination use with dexamethasone can have an anti-tumor effect. It can down-regulate the expression of cell proliferation genes through multiple methods, so as to cure MM, and shows new hope to the target therapy of MM. It can greatly improve the response rate, and prolong the lifetime. Many studies have proved that combination therapy with bortezomib can improve the remission rate of MM effectively. Accompanied with the emergence of these new drugs, many new drugs’combination regimens have been included in the NCCN guidelines, so patients with multiple myeloma have more choices. It is so important to choose a chemotherapy regimen, which can improve efficacy and reduce adverse reactions.Therefore, the observation of clinical efficacy and adverse reactions of BD regimen and traditional VAD regimen is so important, and it can provide reliable basis for the choice of clinical therapy.ObjectiveTo compare the therapeutic effects and side-effects in patients with multiple myeloma who are treated by BD regimen (bortozomib+dexamethasone) and VAD regimen (vincristine+doxorubicin+dexamethasone) or (vindesine+pirarubicin+dexamethasone), and provide reliable basis for the choice of clinical therapy.Methods1.Clinic data:82patients who were diagnosed multiple myeloma from January2008to December2012in Hematology of the first affliliated hospital of Zhengzhou university and Xinyang cenral hospital were analysed retrospectively, and were given regular treatment of BD regimen or VAD regimen2to6cycles.82patients were diagnosed according to the domestic diagnostic criteria for multiple myeloma through the bone marrow cell morphology, serum monoclonal immunoglobulin (M protein), were staged according to the Multiple Myeloma International Staging Standard (ISS) criterion, were classified according to the type of immunoglobulin and light chain, and were divided into BD regimen and VAD regimen according to their treatments. Collecting the information of the82patients, including gender, age, blood routine, serum protein electrophoresis, immunofixation electrophoresis, blood (urine) light chain levels, albumin, P2-microglobulin, electrolyte, urea nitrogen, creatinine, etc. There were no statistical differences of age, sex, stage and type between the two groups. There were36patients in BD group, including20males and16females, IgG20cases, IgA7cases, IgM1cases, light chain8cases (kappa light chain2cases and lambda light chain6cases); stage I3cases, stage Ⅱ10cases, stage Ⅲ23cases. There were46patients in the VAD group, including22males and24females, IgG24cases, IgA12cases, IgM1case, light chain9cases (kappa light chain3cases and lambda light chain6cases); stage15cases, stageⅡ12cases, stage Ⅲ29cases.2. Chemotherapy regimens:BD regimen:bortezomib1.3mg/m2intravenous injection (3-5second) dl, d4, d8, dll;dexamethasone20mg intravenous drip d1,2, d4,5, d8,9, dll,12; then rest10days,21days a period. VAD regimen of the first affiliated hospital of Zhengzhou university:vindesine4mg intravenous injection dl; pirarubicin10md/d intravenous drip d1～4; dexamethasone20mg/d intravenous drip d1～4, d9～12, d17～20,28days a period. VAD regimen of Xinyang central hospital: vincrinstine0.4mg/m2/d continuous intravenous injection24h, d1～4; doxorubicin9mg/m2/d continuous intravenous drip24h, d1～4; dexamethasone40mg/d intravenous drip d1～4, d9～12, d17～20,28days a period. Supporting treatments, such as protecting liver, PPI and antiemetics, were used in the chemotherapy course. The dexamethasone’s dosage was adjusted, depending on patients’age, glucose, blood pressure, infection, tolerance. Disphosphonate drugs were used to cure bone damage. Thalidomide tablets were taked by the patients of the two regimens.3. Obvervation index:the response rate and side effect rate of every regimen group.4. Efficacy criterion:The therapeutic effect and side effects of the two groups were evaluated comprehensively after2to6courses of chemotherapy. IMWG and NCICTCAE criteria were used to access therapeutic effect and side effects respectively.5. Statistical processing:The results were analyzed by SPSS17.0softwareX2test and Fisher exact propability were used to compare the response rate and side effect of the two regimen groups. P<0.05was considered to be statistically significant.Results1. Through2to6courses of BD regimen or VAD regimen chemotherapy, symptoms of multiple myeloma such as bone pain, anemia, renal insufficiency, hypercalcemia were relieved to some extent. BD regimen group:There were an overall response rate80.6%(29/36), CR27.8%(10/36), PR52.8%(19/36), patients with renal insufficiency response rate66.7%(8/12), patients with normal renal function response rate87.5%(21/24), patients with light chain response rate75.0%(6/8), patients without light chain response rate82.1%(23/28), ISS stage Ⅰ and ISS stage Ⅱ patients response rate84.6%(11/13),ISS stage Ⅲpatients response rate78.3%(18/23). VAD regimen group:overall response rate45.7%(21/46), CR8.7%(4/46), PR37.0%(17/46),renal insufficiency patients response rate23.5%(4/17), stable renal function patients response rate58.6%(17/29), light chain type patients response rate22.2%(2/9), patients without light chain response rate51.3%(19/37), ISS stage Ⅰ and ISS stage Ⅱ patients response rate64.7%(11/17), ISS stage Ⅲ patients response rate34.5%(10/29). Response rates were compared by x2test and Fisher exact propability, there was significant difference of the overall response rate between the BD regimen group and VAD regimen group(x2=10.339, P=0.001); and there were significant differences between groups of patients with renal insufficiency(P=0.022) and patients with normal renal function(X2=5.397,P=0.02), as well as light chain type patients(P=0.035), patients without light chain(%2=6.609, P=0.01), and ISS stage III patients(x2=9.702,P=0.002). But there was no significant difference between ISS stage Ⅰ and ISS stage Ⅱ patients (P=0.230).2. The side effects of everey group during the period of chemotherapy:the patients of BD regimen presented the following side effects:hematological toxicity6cases(16.7%); liver function damage1case(2.8%), infection8cases(22.2%),3to4 grade2cases(5.6%); cardiotoxicity0case; peripheral neuropathy10cases(27.8%),3to4grade2cases(5.6%); gastrointestinal reaction5cases(13.9%); weakness5cases (13.9%); edema4cases(11.1%). The patients of VAD regimen appeared side effects: hematological toxicity22cases(47.8%),3to4grade4cases(8.7%); liver function damage9cases(19.6%); infection11cases(23.9%),3to4grade3cases(6.5%); cardiotoxicity7cases(15.2%); peripheral neuropathy10cases(21.7%),3to4grade1cases(2.1%); gastrointestinal reaction19cases(41.3%),3to4grade2cases(4.3%); weakness13cases(28.3%), edema3cases (6.5%). Thirteen out of total36patients received BD regimen experienced side effects(36.1%), and twenty-nine out of total36patients received VAD regimen experienced side effects(63.0%). There was significant difference between the two groups’side effect rate(X2=5.863,P=0.015). BD regimen group had less3to4grade side effect.Conclusion1The overall response rate of BD regimen group is higher than that of VAD regimen group, regardless of renal function and disease’s type. In the treatment of patients with ISS stage Ⅲ the BD regimen is superior to VAD regimen.2Compared to VAD regimen, the side effect of the BD regimen is low and mild during the treatment, and serious side effects are rare.