本文選題：多發(fā)性骨髓瘤 + 硼替佐米　； 參考：《青島大學(xué)》2017年碩士論文

【摘要】：目的:回顧性分析多發(fā)性骨髓瘤(MM)化療療效,進(jìn)一步明確硼替佐米對多發(fā)性骨髓瘤治療有效性;比較含有硼替佐米的化療方案與不含硼替佐米的化療方案療效及不良反應(yīng)的差異;比較硼替佐米不同用藥方式的化療療效及外周神經(jīng)毒性的差異。方法:回顧性分析我院自2005年-2015年診斷MM患者90例,其中男51例,女39例,中位年齡61(49~70)歲。90例患者中,腎功能正�；颊�55例,腎功能不正常患者35例。90例患者按照新發(fā)及復(fù)發(fā)分為:初發(fā)活動型骨髓瘤組(50例),復(fù)發(fā)難治性骨髓瘤組(40例);按化療方案不同分為:硼替唑米組52例(主要化療方案有PAD、PCD、PTD),非硼替唑咪組38例(主要化療方案有:VAD、VCD、VTD)�；颊呓邮芤�(guī)范化療2-4療程;統(tǒng)計患者發(fā)病時的高危FISH檢出率、腎損害例數(shù),化療方案、2療程及4療程后療效、化療相關(guān)副作用。評估:1.硼替佐米組及非硼替佐米組化療療效差異(2療程及4療程),MM患者硼替佐米組不同化療方案(PAD、PCD、PTD)療效的差異;2.硼替佐米組及非硼替佐米組在外周神經(jīng)毒性、血液系統(tǒng)不良、化療后感染、消化系統(tǒng)不良反應(yīng)的差異;3.初發(fā)及復(fù)發(fā)MM患者高危FISH檢出及腎功能損害的恢復(fù)情況;4.硼替佐米皮下注射及靜推注兩種用藥方式化療療效及外周神經(jīng)毒性的差異。結(jié)果:90例患者中,初發(fā)活動型骨髓瘤組50例,復(fù)發(fā)難治性骨髓瘤組40例。1.化療療效方面:(1)化療方案與化療療效的關(guān)系。(1)初發(fā)活動型MM,硼替佐米組(30例)與非硼替佐米組(20例),2療程后總緩解率(ORR)分別為:73.3%、45%(P0.05);4療程后ORR分別為:80%、52.6%(P0.05)。(2)復(fù)發(fā)難治性骨髓瘤組,硼替佐米組(22例)與非硼替佐米組(18例),2療程后ORR分別為:59.1%、27.8%(P0.05);4療程后ORR分別為:66.7%、35.3%(P0.05)。(3)硼替佐米組52例(初發(fā)30例+復(fù)發(fā)22例),分別予以PAD、PCD、PTD方案;初發(fā)活動型骨髓瘤患者硼替佐米組30例,2療程ORR分別為:75%、71.4%、75%(P0.05);4療程ORR分別為:75%、78.6%、87.5%(P0.05);復(fù)發(fā)難治性骨髓瘤患者硼替佐米組22例,2療程ORR分別為:50%、60%、66.7%(P0.05);4療程ORR分別為:66.7%、66.7%、66.7%(P0.05)。(2)硼替佐米用藥方式與化療療效關(guān)系。(1)初發(fā)活動型骨髓瘤組硼替佐米組30例患者,13例患者皮下注射方式給藥,17例靜脈推注方式給藥;化療2及4療程后療程后,皮下注射組及靜脈推注組ORR分別為:76.9%、70.6%(P0.05)及84.6%、76.4%(P0.05);(2)復(fù)發(fā)難治性骨髓瘤組硼替佐米組22例患者,14例患者皮下注射方式給藥,8例靜脈推注方式給藥;化療2及4療程后療程后,皮下注射組及靜脈推注組ORR分別為:64.3%、50%(P0.05)及69.2%、62.5%(P0.05);(3)所有硼替佐米組52例,皮下注射組共27例,靜脈推注組共25例�；�2及4療程后療程后,皮下注射組及靜脈推注組ORR分別為:70.4%、64%(P0.05)及76.9%、72%(P0.05)。(3)高危FISH檢出。初發(fā)活動型MM中39例行FISH檢測,15例檢測出異常,其中高危組3例,復(fù)發(fā)難治性MM中33例行FISH檢測,18例檢測出異常,其中高危組11例。2組高危FISH檢出率比較,P0.05。(4)化療后腎功能改善情況。90例患者腎功能不正常患者35例;硼替佐米組21例,非硼替佐米組14例;治療2療程后,硼替佐米組、非硼替佐米組腎功能總緩解率分別為81.0%、42.9%(P0.05)。2.化療副作用方面:硼替佐米組,多為I~II級、一過性、可逆性的;少數(shù)患者出現(xiàn)III級不良反應(yīng),主要為骨髓抑制(血小板減少為主)、周圍神經(jīng)病變。非硼替佐米組多為I~III級,少數(shù)患者出現(xiàn)Ⅳ級,主要為骨髓抑制(粒細(xì)胞減低、貧血、血小板減少)。(1)外周神經(jīng)毒性方面,皮下注射組27例及靜脈推注組25例,發(fā)生率分別22.2%、52%(P0.05);(2)血液系統(tǒng)不良反應(yīng)方面,硼替佐米組52例及非硼替佐米組38例,發(fā)生率分別為:23.1%、44.7%(P0.05);(3)化療后感染方面,硼替佐米組52例及非硼替佐米組38例,化療后感染率分別為:30.8%、52.6%(P0.05);(4)消化系統(tǒng)不良反應(yīng)方面,硼替佐米組52例及非硼替佐米組38例,消化系統(tǒng)不良反應(yīng)發(fā)生率分別為32.7%、34.2%(P0.05)。結(jié)論:1.含有硼替佐米的化療方案對初發(fā)活動型骨髓瘤及復(fù)發(fā)難治性骨髓瘤均有顯著療效,優(yōu)于非硼替佐米組(P0.05)。2.含有硼替佐米的PAD、PCD、PTD三種方案比較,療效無明顯差異(P0.05)。3.不良反應(yīng)方面:硼替佐米組,在外周神經(jīng)毒性方面高于非硼替佐米組(P0.05);在血液學(xué)不良反應(yīng)、感染發(fā)生方面低于非硼替佐米組(P0.05);在消化道不良反應(yīng)方面,與非硼替佐米組無差異(P0.05)。4.硼替佐米皮下注射與靜脈推注兩種方式給藥比較,療效無明顯差異(P0.05);皮下注射組外周神經(jīng)毒性發(fā)生率低于靜脈推注組(P0.05)。5.硼替佐米組腎損害改善優(yōu)于非硼替佐米組(P0.05)。6.復(fù)發(fā)難治性骨髓瘤組高危FISH檢查率高于初發(fā)活動型多發(fā)性骨髓瘤組(P0.05)。
[Abstract]:Objective: To review the therapeutic effect of multiple myeloma (MM), and to further clarify the efficacy of bortezomizomi in the treatment of multiple myeloma, compare the effect of bortezomib chemotherapy with the chemotherapy regimen without bortezomib and the difference in adverse reactions; compare the therapeutic effect and peripheral neurotoxicity of bortezomizo in different ways of drug use Methods: a retrospective analysis of 90 patients with MM in -2015 2005, including 51 male, 39 female, 61 (49~70) year old.90 patients, 55 cases of normal renal function and 35 cases of renal dysfunction in.90 patients were divided into primary active myeloma group (50 cases) and relapsed refractory myeloma group (50 cases). 40 cases were divided into 40 cases: 52 cases of bortezolm group (PAD, PCD, PTD) and 38 cases of non bortezolomi group (major chemotherapy regimens: VAD, VCD, VTD). The patients received standardized chemotherapy for 2-4 courses; the high risk FISH detection rate, the number of renal damage, the chemotherapy regimen, the 2 course of treatment and the 4 course of chemotherapy, the chemotherapy related side 1. bortezomizomi group and non bortezomizomi group (2 course and 4 course of treatment), different chemotherapy regimens (PAD, PCD, PTD) in bortezomizomi group of MM patients; 2. bortezomizomi group and non bortezomizomi group in peripheral neurotoxicity, poor blood system, postoperative infection, and the difference of digestive system adverse reaction; 3. first hair And the recovery of high risk FISH detection and renal function damage in patients with recurrent MM, 4. bortezomizomi subcutaneous injection and two kinds of intravenous injection of chemotherapy effect and peripheral neurotoxicity. Results: in 90 patients, 50 cases of primary active myeloma group, 40 cases of relapsed refractory myeloma group with.1. chemotherapy: (1) chemotherapy and chemotherapy The relationship of curative effect. (1) primary active MM, bortezomizomi group (30 cases) and non bortezomib group (20 cases), the total remission rate (ORR) after 2 courses were 73.3%, 45% (P0.05), and ORR after 4 courses were 80%, 52.6% (2), relapsed refractory myeloma group, bortezomizomi group (22 cases) and non bortezomizomi group (18 cases), and ORR after 2 courses respectively: 59.1%, respectively after 2 courses respectively ( P0.05); after 4 course of treatment, ORR was respectively: 66.7%, 35.3% (P0.05). (3) 52 cases of bortezomizomi group (30 cases of early onset + 22 cases), respectively, PAD, PCD, PTD scheme, bortezomizomi group 30 cases of primary active myeloma, 2 course of ORR respectively: 75%, 71.4%, 75% (P0.05); 4 course ORR respectively: recurrent refractory myeloma patients bortex Zomi group 22 cases, 2 courses of ORR were 50%, 60%, 66.7% (P0.05), 4 courses of ORR were 66.7%, 66.7%, 66.7% (P0.05). (2) bortezomizomizomizomi group, 30 patients, 13 cases of subcutaneous injection and intravenous injection; chemotherapy and treatment course of treatment After the subcutaneous injection and intravenous injection group ORR were 76.9%, 70.6% (P0.05) and 84.6%, 76.4% (P0.05); (2) 22 patients in the bortezomizomi group with relapsed refractory myeloma group, 14 patients with subcutaneous injection and 8 intravenous injection; after the chemotherapy for 2 and 4 courses, the subcutaneous injection group and the intravenous group ORR were respectively: 64.3%, 50% (P 0.05) and 69.2%, 62.5% (P0.05); (3) all bortezomizo group 52 cases, subcutaneous injection group 27 cases, intravenous injection group 25 cases. After chemotherapy 2 and 4 course of treatment, the subcutaneous injection group and intravenous injection group ORR were 70.4%, 64% (P0.05) and 76.9%, 72% (P0.05). (3) high risk FISH detection. Primary active MM routine FISH detection, abnormal detection of abnormal, Among them, 3 cases were high risk group, 33 cases of relapsed refractory MM were detected by FISH, 18 cases were detected abnormality, among which 11 cases of high risk group were at high risk of high risk of FISH, P0.05. (4) after chemotherapy, 35 cases of renal dysfunction in patients with renal function after chemotherapy, 21 cases in bortezomizomi group and 14 cases of bortezomizomi group, bortezomizomi group, bortezomizomi group and bortezomib after the 2 course of treatment. The total remission rate of kidney function in Zomi group was 81%, 42.9% (P0.05).2. chemotherapy side effects: bortezomizomi group, more I~II grade, one over, reversible, and a few patients with III side effects, mainly myelosuppression (thrombocytopenia), peripheral neuropathy, non bortezomizomi group more I~III, and a few patients with grade IV Bone marrow suppression (granulocytopenia, anemia, thrombocytopenia). (1) peripheral neurotoxicity, 27 cases in subcutaneous injection group and 25 cases of intravenous injection group, 22.2%, 52% (P0.05); (2) blood system adverse reactions, bortezomizomi group 52 cases and non bortezomizomi group 38 cases, 23.1%, 44.7% (P0.05); (3) postoperative induction of chemotherapy Infection, bortezomizomi group 52 cases and non bortezomizomi group 38 cases, after chemotherapy, the infection rate was 30.8%, 52.6% (P0.05), (4) the digestive system adverse reaction, bortezomizomi group 52 cases and non bortezomizomi group 38 cases, the incidence of digestive system adverse reaction was 32.7%, 34.2% (P0.05). Conclusion: 1. containing bortezomib chemotherapy scheme to the first hair Active myeloma and relapsed refractory myeloma had a significant effect. Compared with the three schemes of bortezomizomi (P0.05).2. containing bortezomib, PAD, PCD, and PTD, there was no significant difference (P0.05) in the adverse reaction of.3.: bortezomizomizomi group was higher than that of the non bortezomizomi group (P0.05); in the hematological adverse reactions, the peripheral neurotoxicity of bortezomizomizomizomizomi was not significantly different. The incidence of infection was lower than that of the non bortezomizomi group (P0.05), and there was no difference between the two ways of subcutaneous injection of bortezomizomi and intravenous injection of bortezomizomi (P0.05) in the digestive tract adverse reactions (P0.05), and the incidence of peripheral neurotoxicity in subcutaneous injection group was lower than that of intravenous bortezomib (P0.05).5. bortezomizomi (P0.05). Renal damage in group A was better than that in non bortezomib group (P0.05). The rate of high risk FISH in.6. relapsed refractory myeloma group was higher than that in the early active multiple myeloma group (P0.05).
【學(xué)位授予單位】：青島大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R733.3

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