高白细胞血症

Hyperleukocytosisand

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

leukemiatypeandpatientpopulation.

large,poorlydeformableblastsininfants,agesof10and20years,males,Tcellphenotype病因端粒酶ATRT，三氧化二砷机理

1.白细胞可塑性小，变性能力差，过高的白细胞在微循环中大量淤滞，导致血流减慢，血液粘滞度增高，特别易在脑、肺、肾、腹腔血管梗塞，预后很差。

2.白血病细胞耗氧量高，导致组织缺氧，加之白血病细胞浸润破坏血管壁致脏器出血、水肿，更由于血小板计数减少和大量白血病细胞崩解释放出促凝血物质，极易形成DIC。SIGNSANDSYMPTOMSthemainclinicalsymptomsofleukostasisandcausesofearlydeatharerelatedtoinvolvementofthecentralnervoussystem(40%)lungs(30%)Pulmonarysignsandsymptoms

dyspneaandhypoxiawithorwithoutdiffuseinterstitialoralveolarinfiltratesonimagingstudies.MeasurementofthearterialpO2canbefalselydecreasedsincetheWBCsinthetesttubeutilizeoxygen.PulseoximetryprovidesamoreaccurateassessmentofO2saturationinthissetting.Neurologicalsignsandsymptomsvisualchanges,headache,dizziness(头晕),tinnitus（耳鸣）,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：足量液体2000～3000ml/m2.d碱化：予5%碳酸氢钠80-100ml/m2.d，使尿PH＞7去白ALL1、ALL

在诱导缓解治疗之前应用肾上腺激素并逐渐加量，如强的松由15mg/m2渐增至30mg/m2,50mg/m2,75mg/m2,100mg/m2，一般需一周待白细胞降至50×109/L，可考虑加用其他种类化疗药物。多数研究表明，儿童ALL诊断时白细胞≥50×109/L为判断预后的独立危险因素之一。但部分高细胞ALL被强化疗克服，相当一部分患儿仍可获长期无病存活。

德国BFM-95方案中，儿童ALL白细胞≥20×109/L；年龄≥1岁，≤6岁；免疫分型T细胞型ALL定为中危组，5年无病生存率仍达70%。Cytoreduction1.chemotherapy(hydroxyurea羟基脲orremissioninductionchemotherapy诱导缓解化疗)——theonlytreatmentproventoimprovesurvival50to100mg/kg/dpo,↓WBC50-80%(24-48h),2to4grams,q12,po,＜50x109/LRarecomplicationsincludefeverandabnormalliverfunctiontests.Hydroxyureashouldnotbeusedinpregnancyorinwomenwhoarebreastfeeding.2.leukapheresis(白细胞分离)respiratoryfailureandneurologiccompromisearepresent，facilitiesareavailable,wesuggestleukapheresisforpatientswithleukemicblastcountsgreaterthan50to100x109/LSupportivecare1.TLS：UA、K、P↑，Ca↓intravenoushydrationtoensureadequateurineflow

allopurinol(别嘌醇)orrasburiscase（拉布立酶),↓UAcorrectionofanyelectrolytedisturbancesorcausesofreversiblerenalfailure.2.Coagulationabnormalities:DIC,Fbg↓，FDPs、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)拉布立酶重组尿酸氧化酶recombinanturateoxidase)尿酸氧化酶(urateoxidase)广泛存在于非灵长类动物的体内，首先从黄曲霉菌中被分离出来，它可将尿酸进一步氧化为尿素囊(allantoin)及过氧化氢(H202)(见图1)，前者的水溶性是尿酸的5～10倍，以终产物形式稳定从肾脏排出。非重组尿酸氧化酶，可有效降低患者血尿酸水平，并且将透析率由16％～23％降至0％～2．6％。但非重组尿酸氧化酶的过敏反应发生率为4．5％～5％，限制了其临床应用。1996年研究者将黄曲霉菌中编码尿酸氧化酶的基因转移并表达于酿酒酵母菌中，成功研发出重组尿酸氧化酶一拉布立酶(resburicase)，明显减少了过敏反应的发生2001年Goldman等报道了拉布立酶的首个、也是迄今为止唯一的多中心、开放性、Ⅲ期随机对照研究，对比有TLS风险的儿童进展期NHL及ALL患者分别使用拉布立酶及别嘌呤醇的临床疗效。结果发现拉布立酶首剂4小时后实验组及对照组尿酸水平分别下降86％及12％，；血浆尿酸分别128士70mg／dl／h及329±129mg／dl／h，P<0．0001。拉布立酶一般在化疗药物前使用，推荐剂量：0．2mg／kg，溶于0．9％生理盐水中静脉输注30分钟；从化疗首日开始，连续使用5～7天。药物半衰期为22小时，肝、肾功能异常患者无需减量。用药24小时内需密切监测血磷酸、血钾、血钙及UA水平，警惕TLS的发生，一般推荐每4小时检测