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1、授予單位代碼10089學(xué)號或申請?zhí)?0153416中國圖書分類號R733.4HebeiMedicalUniversity碩士學(xué)位論文專業(yè)學(xué)位ALK陽性間變大細(xì)胞淋巴瘤診治及未來治療策略的探索研究生：賀世超導(dǎo)師：江蓮教授專業(yè)：兒科學(xué)二級學(xué)院：第四醫(yī)院2018年3月目錄中文摘要··············································································································1英文摘要······················
2、························································································3英文縮寫··············································································································4綜述ALK陽性間變大細(xì)胞淋巴瘤診治及未來治療策略的探索···········5致謝·····························
3、·················································································25個人簡歷··············································································································26中文摘要ALK陽性間變大細(xì)胞淋巴瘤診治及未來治療策略的探索摘要ALK陽性間變大細(xì)胞淋巴瘤（ALK+ALCL）是一種具有較強(qiáng)侵襲性的T細(xì)胞淋巴瘤，占兒童
4、淋巴瘤的10%-15%，目前常規(guī)的化療方案獲得了優(yōu)異的結(jié)果，使約90%的患兒得到緩解，但緩解后復(fù)發(fā)/耐藥率高也是本病的特點(diǎn)。對于預(yù)后不良、復(fù)發(fā)難治的患者，二線方案治療取得了一定進(jìn)展(如DHAP、ESHAP、ICE、miniBEAM和MINE等方案的應(yīng)用)，聯(lián)合CR后自體造血干細(xì)胞移植或異基因造血干細(xì)胞移植，取得了一定療效。同時隨著抗CD30抑制劑及第一代ALK抑制劑（克唑替尼）的應(yīng)用，一些復(fù)發(fā)/耐藥患兒再次取得緩解，但仍有約30%患兒對克唑替尼耐藥，第二、三代ALK抑制劑應(yīng)用于ALK陽性其他腫瘤的臨床研究也取得了一定的效果，因其在臨床應(yīng)用時發(fā)
5、現(xiàn)仍有一定的耐藥性，故第二、三代抑制劑暫未應(yīng)用于間變大細(xì)胞淋巴瘤中。但關(guān)于該病的未來其他治療策略正在研究當(dāng)中，如：ALK抑制劑與其他抑制劑聯(lián)合靶向治療及免疫治療，通過調(diào)節(jié)DNA損傷反應(yīng)（DDR）及DNA修復(fù)途徑維持細(xì)胞穩(wěn)定性，通過影響自噬途徑調(diào)節(jié)腫瘤細(xì)胞死亡等未來可能的治療策略均取得了一定的進(jìn)展，自噬與ALK抑制劑聯(lián)合應(yīng)用可能是未來治療本病的一種新的策略。相信隨著臨床與基礎(chǔ)研究的不斷深入，ALK陽性間變大細(xì)胞淋巴瘤遠(yuǎn)期預(yù)后會得到明顯改善。關(guān)鍵詞：ALK陽性,間變大細(xì)胞瘤,復(fù)發(fā)/耐藥，靶向治療,新策略1英文摘要TheDiagnosisandTr
6、eatmentofALK-positiveAnaplasticlargecelllymphomaanditsfuturenewstrategyABSTRACTALK-positiveintercelluarlymphoma(ALK+ALCL)isahighlyaggressiveT-celllymphomathataccountsfor10%to15%ofchildhoodlymphomas.Currentconventionalchemotherapyregimenshaveyieldedexcellentresults.Ninetyper
7、centofthechildrenwererelieved,buttherelapse/highresistancerateafterremissionwasalsoafeatureofthedisease.Forpatientswithpoorprognosisandrelapseandincurability,second-lineregimentreatmenthasachievedsomeprogress(suchastheapplicationofDHAP,ESHAP,ICE,miniBEAM,andMINE),andautolog
8、oushematopoieticstemcelltransplantationorallogeneichematopoieticstemcelltransplant
