Hyperleukocytosisand

leukostasisHyperleukocytosisreferstoalaboratoryabnormalitythathasbeenvariablydefinedasatotalleukemiabloodcellcountgreaterthan50-100x109/L(100,000/microL)..INTRODUCTIONINTRODUCTIONleukostasisalsocalledsymptomatichyperleukocytosisamedicalemergency,apathologicdiagnosistheone-weekmortalityrateisapproximately20to40percent.EPIDEMIOLOGY

leukemiatypeandpatientpopulation.

large,poorlydeformableblastsininfants,agesof10and20years,males,Tcellphenotype病因端粒酶ATRT，三氧化二砷機理

1.白細胞可塑性小，變性能力差，過高的白細胞在微循環(huán)中大量淤滯，導致血流減慢，血液粘滯度增高，特別易在腦、肺、腎、腹腔血管梗塞，預(yù)后很差。

2.白血病細胞耗氧量高，導致組織缺氧，加之白血病細胞浸潤破壞血管壁致臟器出血、水腫，更由于血小板計數(shù)減少和大量白血病細胞崩解釋放出促凝血物質(zhì)，極易形成DIC。SIGNSANDSYMPTOMSthemainclinicalsymptomsofleukostasisandcausesofearlydeatharerelatedtoinvolvementofthecentralnervoussystem(40%)lungs(30%)Pulmonarysignsandsymptoms

dyspneaandhypoxiawithorwithoutdiffuseinterstitialoralveolarinfiltratesonimagingstudies.MeasurementofthearterialpO2canbefalselydecreasedsincetheWBCsinthetesttubeutilizeoxygen.PulseoximetryprovidesamoreaccurateassessmentofO2saturationinthissetting.Neurologicalsignsandsymptomsvisualchanges,headache,dizziness(頭暈),tinnitus（耳鳴）,gaitinstability,confusion,somnolence（嗜睡）,and,occasionally,coma（昏迷）.anincreasedriskofintracranialhemorrhagethatpersistsforatleastaweekafterthereductionofwhitecellcount（reperfusioninjury）noncontrastedCTorMRIisindicatedinpatientswithneurologicabnormalities.cautiousaboutusingintravenouscontrastdyeatatimewhenrenalfunctionmaybecompromisedbyleukostasisortumorlysissyndrome,anddehydration.fever（80%）inflammationassociatedwithleukostasisconcurrentinfection.treatempiricallyforinfectioninallsuchpatientsLesscommonsignsorsymptoms：

electrocardiographicsignsofmyocardialischemiaorrightventricularoverloadworseningrenalinsufficiencypriapism,acutelimbischemia,orbowelinfarctionDIAGNOSISLeukostasis(symptomatichyperleukocytosis)isdiagnosedempiricallywhenapatientwithleukemiaandawhitebloodcell(WBC)countover100x109/L(100,000/microL)presentswithsymptomsthoughttobeduetotissuehypoxia,mostcommonlyrespiratoryorneurologicaldistress.MANAGEMENT水化：足量液體2000～3000ml/m2.d堿化：予5%碳酸氫鈉80-100ml/m2.d，使尿PH＞7去白ALL1、ALL

在誘導緩解治療之前應(yīng)用腎上腺激素并逐漸加量，如強的松由15mg/m2漸增至30mg/m2,50mg/m2,75mg/m2,100mg/m2，一般需一周待白細胞降至50×109/L，可考慮加用其他種類化療藥物。多數(shù)研究表明，兒童ALL診斷時白細胞≥50×109/L為判斷預(yù)后的獨立危險因素之一。但部分高細胞ALL被強化療克服，相當一部分患兒仍可獲長期無病存活。

德國BFM-95方案中，兒童ALL白細胞≥20×109/L；年齡≥1歲，≤6歲；免疫分型T細胞型ALL定為中危組，5年無病生存率仍達70%。Cytoreduction1.chemotherapy(hydroxyurea羥基脲orremissioninductionchemotherapy誘導緩解化療)——theonlytreatmentproventoimprovesurvival50to100mg/kg/dpo,↓WBC50-80%(24-48h),2to4grams,q12,po,＜50x109/LRarecomplicationsincludefeverandabnormalliverfunctiontests.Hydroxyureashouldnotbeusedinpregnancyorinwomenwhoarebreastfeeding.2.leukapheresis(白細胞分離)respiratoryfailureandneurologiccompromisearepresent，facilitiesareavailable,wesuggestleukapheresisforpatientswithleukemicblastcountsgreaterthan50to100x109/LSupportivecare1.TLS：UA、K、P↑，Ca↓intravenoushydrationtoensureadequateurineflow

allopurinol(別嘌醇)orrasburiscase（拉布立酶),↓UAcorrectionofanyelectrolytedisturbancesorcausesofreversiblerenalfailure.2.Coagulationabnormalities:DIC,Fbg↓，F(xiàn)DPs、D-dimer↑3.redbloodcelltransfusions:begivenslowly,overafewhours,orduringtheleukapheresisprocedure，Hydrationencouraged,diureticsdiscouraged4.platelettransfusions:＞20to30,000/microLPROGNOSISdependsuponthetypeofleukemiaandthepresenceofsymptoms.Themortalityrateisunrelatedtothelevelofthewhitebloodcellcount,butpatientswithsymptomsAML：initialmortalityrate20-40%patientswholivedmorethanoneweekVS.patientswhodiedwithinthefirstweek(retrospectiveanalysis1977)coagulopathy(64vs.18%)respiratorydistress(100vs.15%)renalfailure(43vs.29%)neurologicsymptoms(64vs.12%)ALLhyperleukocytosisisrarelycomplicatedbyleukostasisinchildhoodALL,theearlydeathrate＜5percentThechallenge:TLS,DIC,andthehigherriskofrelapse(approximately50percentbyfouryears)拉布立酶重組尿酸氧化酶recombinanturateoxidase)尿酸氧化酶(urateoxidase)廣泛存在于非靈長類動物的體內(nèi)，首先從黃曲霉菌中被分離出來，它可將尿酸進一步氧化為尿素囊(allantoin)及過氧化氫(H202)(見圖1)，前者的水溶性是尿酸的5～10倍，以終產(chǎn)物形式穩(wěn)定從腎臟排出。非重組尿酸氧化酶，可有效降低患者血尿酸水平，并且將透析率由16％～23％降至0％～2．6％。但非重組尿酸氧化酶的過敏反應(yīng)發(fā)生率為4．5％～5％，限制了其臨床應(yīng)用。1996年研究者將黃曲霉菌中編碼尿酸氧化酶的基因轉(zhuǎn)移并表達于釀酒酵母菌中，成功研發(fā)出重組尿酸氧化酶一拉布立酶(resburicase)，明顯減少了過敏反應(yīng)的發(fā)生2001年Goldman等報道了拉布立酶的首個、也是迄今為止唯一的多中心、開放性、Ⅲ期隨機對照研究，對比有TLS風險的兒童進展期NHL及ALL患者分別使用拉布立酶及別嘌呤醇的臨床療效。結(jié)果發(fā)現(xiàn)拉布立酶首劑4小時后實驗組及對照組尿酸水平分別下降86％及12％，；血漿尿酸分別128士70mg／dl／h及329±129mg／dl／h，P<0．0001。拉布立酶一般在化療藥物前使用，推薦劑量：0．2mg／kg，溶于0．9％生理鹽水中靜脈輸注30分鐘；從化療首日開始，連續(xù)使用5～7天。藥物半衰期為22小時，肝、腎功能異常患者無需減量。用藥24小時內(nèi)需密切監(jiān)測血磷酸、血鉀、血鈣及UA水平，警惕TLS的發(fā)生，一般推薦每4小時檢測