Leukemia(白血病)謝毅（Xieyi）

Dep.Hematology，HuashanHospital2026/1/151xieYi,HuaShanHospitalConceptofleukemiaDefinitionItistheresultsofthetumorproliferationofheamotopoieticstemcells.（造血干細(xì)胞）Leukemiaisamalignantblooddisorder.(notsolidtumor)

2026/1/152xieYi,HuaShanHospitalHeamatopoieticstemcell

reproductionHSClymphoidHSCHSCdifferentiation

earlyprogenitorCFU-GEMM

myeloidHSCHeamatopoieticStemCell(HSC)istheprimarycellofHeamatopoieticsystemandimmunesystem.2026/1/153xieYi,HuaShanHospital2026/1/154xieYi,HuaShanHospitalTumorproliferationofHSC

DifferentiationofHSCisblocked.LeukemiacellsarestoppedonadifferentiationstageofHSC&lackofthenormalfunction.Proliferationisoutofcontrolandapoptosisisinhibited.Leukemiacellisclonedandaccumulatedinagreatquantity.infiltrationandmetastasis2026/1/155xieYi,HuaShanHospitalmalignantblooddisorders

HSCdifferentiationisblocked.Normalbloodcellsaredecreasedandleukemiacellisincreased.ThefunctionofBloodandimmunesystemareshortof.Fever，bleeding，anemia2026/1/156xieYi,HuaShanHospitalmalignantblooddisorders

Proliferationisoutofcontrol,apoptosisisinhibitedandleukemiacellisaccumulatedinagreatquantity.Leukostasis(白細(xì)胞淤滯)AbnormalmorphologypicturesofbloodandbonemarrowLiver,spleen,lymphnods,skin,CNSareinfiltratedanddysfunctionalfrequently.2026/1/157xieYi,HuaShanHospitalAccordingtothe

acutemyeloidleukemia（AML）Differentiation&

M0M1M2………………..M7KindofcellblastcrisisofCML，mastcellleukemia，

acuteeosinophilicleukemia，basophilic…………

leukemia

acutelymphocyteleukemia（ALL）

L1，L2，L3T－ALL、B－ALL

chronic

leukemia：CML、P－LL、CLL、HCL、……

leukemia

the

traditionclassification(FAB)ofleukemia2026/1/158xieYi,HuaShanHospitalWHOclassification(2001)1,Acutemyeloidleukemia(AML)(1),AMLwithrecurrentcytogeneticabnormalitiesAMLwitht(8;21)(q22;q22),(AML1/ETO)AMLwitht(15;17)(q22;q12),(PML/RAR

)AMLwithinv(16)(p13;q22)ort(16;16)(p13;q22),CBF/MYH11AMLwith11q23(MLL)abnormalities2026/1/159xieYi,HuaShanHospital

WHOclassification(2001)

(2),AMLwithmultilineagedysplasiaWithpriormyelodysplasticsyndromeWithoutpriormyelodysplasticsyndrome(3),AMLandmyelodysplasticsyndrome,therapyrelatedAlkylatingagentrelatedTopoisomerasellinhibitor-related2026/1/1510xieYi,HuaShanHospital

WHOclassification(2001)(4)

AMLnototherwisecategorizedAMLminimallydifferentiationAMLwithoutmaturationAMLwithmaturationAcutemyelomonocyticleukemiaAcutemonoblasticandmonocyticleukemiaAcuteerythroidleukemiaAcutemegakaryoblasticleukemiaAcutebasophilicleukemiaAcutepanmyelosiswithmyelofibrosisMyeloidsarcoma(5)Acuteleukemiaofambiguouslineage2026/1/1511xieYi,HuaShanHospitalWHOclassification(2001)2,chronicmyeloidleukemia(1),chronicmyeloproliferativediseasechronicmyelogenousleukemiaChronicneutrophilicleukemiaChroniceosinophilicleukemia/hypereosinophilicsyndrome(2),myelodysplastic/myeloproliferativediseaseChronicmyelomonocyticleukemiaAtypicalchronicmyeloidleukemiaJuvenilemyelomonocyticleukemia2026/1/1512xieYi,HuaShanHospitalWHOclassification(2001)3,B-cellneoplasms(1),PrecursorB-cellneoplasmPrecursorBlymphoblasticleukemia(2),MatureB-cellneoplasmChroniclymphocyticleukemia/Smalllymphocyticlymphoma(CLL/SLL)B-cellprolymphocyticleukemiaHairycellleukemiaBurkittlymphoma/leukemia2026/1/1513xieYi,HuaShanHospitalWHOclassification(2001)4,T-cellandNK-cellneoplasms(1),PrecursorT-cellneoplasmPrecursorTlymphoblasticleukemia(2),MatureT-cellandNK-cellneoplasmsT-cellprolymphocyticleukemiaT-celllargegranularlymphocyticleukemiaAggressiveNKleukemia/lymphomaAdultT-cellleukemia/lymphoma2026/1/1514xieYi,HuaShanHospitalEpidemiology:incidence3/105

，increasewithyears?acute>chronic

,AML>ALLSpecialdistribution:Sexman：female＝2：1AgeALL,adolescent80％<20y;

AML,

adult

CML,20~50yearsold;

CLL,50~70yearsoldAreaadultTlymphocyticleukemiaCML,easterncountriesCLL,westerncountries2026/1/1515xieYi,HuaShanHospitalEpidemiology:

mortality2.51/105Areacity>thecountrysideChina<Singapore<Japan<USA<unitedKingdom<Sweden(7.5～9/105)Inorderofthemortalityofmalignanttumorsin1～14y，leukemiaismosthighin15～44y，leukemiaisthirdhigh(<stomachCa<liverCa)inallperson,leukemiaissixthoreighthhigh2026/1/1516xieYi,HuaShanHospitalEtiologyradiation

1、atombomb（長崎）1Km1.5km2km

×100

×22×2.62、highdoseXradiation、32Ptherapy2026/1/1517xieYi,HuaShanHospitalEtiologychemicalsbenzeneTherapy-relatedleukemia

47/440000

2026/1/1518xieYi,HuaShanHospital

virus

ATLV，1981，Japan(鹿兒島)

electricmicroscope：virusC

TheserumantibodytiterofATLVdecreasewiththedistancefrom鹿兒島Etiology2026/1/1519xieYi,HuaShanHospital

Genetics

twin(sameegg)0.2~0.25sibling10/105

Down‘ssyndrome(21+)

40－60/105

Fanconianemia

4/66Etiology2026/1/1520xieYi,HuaShanHospital

fromotherblooddisordersMyeloproliferativeDisease

chronicmyeloidleukemia(CML)polycythemiavera(PV)

primarythrombocythemia(PT)myelofibrosis(MF)

myelodysplasticsyndrome(MDS)

paroxysmalnocturnalhemoglobinuria(PNH)

lymphomaormyelomaEtiology

2026/1/1521xieYi,HuaShanHospitalMechanismRadiation,chemicals,virus,genetics&otherblooddisordersChromosometranslocation

FusiongeneformationFusionprotein（enzyme……）MalignantbiologicbehaviorsMalignantblooddisorders2026/1/1522xieYi,HuaShanHospitalAcuteleukemiaClinicalmanifestation1,fever、bleeding、anemia2、infiltration3、Abnormalmorphologypicturesofbloodandbonemarrow2026/1/1523xieYi,HuaShanHospital

normalWBC↓→immune↓(～AIDS)→feverTheplacewhereskinandmucosameet:respiratorytube,mouth,perineum,anusInflammatoryreactionisweaklyG－B(psuedomonas

aeruginosa……),interstitialpneumonia(peumosystisarinii,CMV，herpesvirus),candidaPLT↓

bleeding

skin,mucosaorcranialcavityRBC↓

anemia1,fever、bleeding、anemia2026/1/1524xieYi,HuaShanHospital2、infiltrationHepatomegaly,splenomegaly,lymphadenopathy,sternaltendernessSpecialinfiltrationareaChloromas:skin,orbit(granulocyticsarcoma)Painlessenlargementoftesticle(ALL)CNSinvolvement,paraplegia(ALL,M4,M5)

gingivitis(M4,M5)

2026/1/1525xieYi,HuaShanHospital3、AbnormalmorphologypicturesofbloodandbonemarrowBlood：WBCfrom<1×109/L(nonleukemoid)to>100×109/L(hyperleukocytosis),blastsarepresent,anemia,PLT↓BM：proliferative(orhypoplastic)，blasts>30%,

Auer‘srods(+),

erythropoiesis↓，megakaryocytopoiesis↓2026/1/1526xieYi,HuaShanHospitalNormalbonemarrowcell2026/1/1527xieYi,HuaShanHospitalleukemiacells(showAuer’srods)2026/1/1528xieYi,HuaShanHospitalClinic

DiagnosisofALThenormalbloodcell↓andluekemiacell↑areshownbyclinicalsigns,symptoms,laboratoryfeaturesandspecialexaminations.blastmorethan30%innonerythrocyticcells(NEC)ofbonemarrowsmear2026/1/1529xieYi,HuaShanHospitalMICMTYPINGDIAGNOSISMICMMorphologyImmunologyCytogeneticsMolecular2026/1/1530xieYi,HuaShanHospitalmorphology

lymphoblastmyeloblastmonoblastplasma少，透明中，Auer‘s多，泡沫樣chromatin粗粒細(xì)砂 細(xì)chromosome短粗細(xì)長

粗 Accompany破碎C,幼淋粒系幼單,成熟單POX － ＋/＋＋粗粒－/＋細(xì)粒NSE － －/+,NaF不抑制＋,NaF抑制PAS 粗粒－結(jié)塊彌漫一片紅鐘表面樣2026/1/1531xieYi,HuaShanHospitalIMMUNO-PHENOTYPING

mab M1 M2 M3 M4 M5 M6 M7CD13 + + + + + - -CD33 + + + + + - -CD14 - ± - + + - -CD41 - - - - - - +Ret - - - - - + -Lectoferrin- + - + - - - CD19 CD7 HLA-DR CD2 MPO T - + - + - B + - + - -2026/1/1532xieYi,HuaShanHospital

Chromosometranslocation

M1+8,-5,-7 inv(3)M2t(8;21)t(6;9)M3t(15;17)M4inv(16)M5t(4;11),t(8;16)M6M7ALL t(9;22)(B)t(8;14)2026/1/1533xieYi,HuaShanHospitalFusiongenemolecularAML1/ETOPML/RAR

CBF/MYH11MLLabnormalitesBCR/ABL2026/1/1534xieYi,HuaShanHospitalMICMTYPINGDIAGNOSIS

WecouldusetraditionaltypingdiagnosisaswhatFABasked.Ifthesituationpermit,wecoulduseFCM,chromosome,PCRorFISHinaWHOtypingdiagnosisway.2026/1/1535xieYi,HuaShanHospitalDifferentialDiagnosisMyelodysplasticsyndrome(MDS)

refractoryanemiaorpancytopenia,BM:dysplasia,blasts<30%Leukemoidreaction

matureleukocytesproliferativewouldplayamainrole,NAP↑,ifprogenitorincrease,onlyshortlyontimeCML:matureprogenitors↑

E↑、B↑，NAP=0,ph'(＋)，bcr-abl(+)Stomatitis，Infectiousmononucleosis，ITP,AA，agranulocytopenia

Thereisnoblastsinbonemarrow2026/1/1536xieYi,HuaShanHospitalprinciple:early，combine，full，interval，bystageswhyearly?Theoverhyperplasia&infiltrationcouldbringthedifficultyontherapy

TumorlysisLeukemiacellenterintotheareaprotectedbythebarrierbetweenbloodandbrain

Couldmakeanti-infection,supportandchemotherapytobedoneatsametimeifitwerenecessary2026/1/1537xieYi,HuaShanHospitalprinciple:early，combine，full，interval，bystagesuseCombinationregimenofthesedrugswhichhavedifferentaction,

typingandtoxicity

toincrease

curativeeffectanddecreasetoxicity

2026/1/1538xieYi,HuaShanHospitalDifferentActionofDrugs嘌呤堿嘧啶堿6MP6TGMTX 氮雜胞苷核苷酸

MTXHU

脫氧核苷酸 VM26

Ara-C,CC

蒽環(huán)類抗生素

DNA破壞烷化劑，CCNUAMSARNADNAL－ASPVCR,VM26

protein子細(xì)胞DNA蒽環(huán)類：阿霉素，表阿霉素，柔紅，阿克拉，米妥蒽醌烷化劑：CTX，氮芥，BU，CB1348，CCNU，BCNUVP162026/1/1539xieYi,HuaShanHospitalCellcycleandchemotherapy

endcell

apoptosis

Go(sourceofrelapse)

sensitiveinsensitiveG1SG2M2026/1/1540xieYi,HuaShanHospitalThedrugtyping

CCSA CCNSAAntimetabolicdrugs alkylatingdrugsS,6MP,6TG mustine，CTX，BU

Ara-C,CC,MTX CB1348，ＣＣＮＵ

HU,VP16 anthracyclineantibioticsM,VCR,VDS,VM26 bleomycinA5(平陽霉素)G1,L-ASP,prednisoneharringtonine(三尖杉)G2,VP16 2026/1/1541xieYi,HuaShanHospital

CCSA CCNSAeffect

dosagedosage

theeffectisincreasedbytimetheeffectincreasedbydosageThedrug‘seffect2026/1/1542xieYi,HuaShanHospitalThetoxicityofthedrugs

烷化劑 抗代謝類VCR三尖杉激素蒽環(huán)類BM抑制 ＋＋＋ ＋＋＋－＋＋－＋＋＋脫發(fā)＋＋ ＋ ＋＋＋口腔潰瘍 ＋＋＋

胃腸反應(yīng) ＋＋＋＋＋ ＋＋＋周圍N炎 ＋＋＋

心毒 ＋＋

＋＋＋免疫抑制＋＋＋＋＋＋＋＋＋＋＋＋＋＋誘變畸變 √ √ √√√√出血性膀胱炎＋＋＋

肝毒 ＋ ＋ ＋＋＋2026/1/1543xieYi,HuaShanHospitalprinciple:early，combine，full，interval，bystagesfull

thedrugshouldworkinallperiodofcellcyclethedosageshouldbefullTheregimenwouldbeusedrepeatedly,

KillingthecellsinallperiodofcellcyclerepeatedlycouldmakeG0→cycle&controlthesourceofrelapse（MRD)2026/1/1544xieYi,HuaShanHospitalprinciple:early，combine，full，interval，by

stagesInterval

for3~4weeksbeforenexttherapy

Leukemiacellnormalcell

Whengetdisease

thegreaterpartofcellshyperplasiaisinhibited

isnotinG0period

easilykilledbychemotherapyinG0periodornot?doublingtime

longshortRecoverinintervalnoteasytorecovereasytorecover

2026/1/1545xieYi,HuaShanHospitalprinciple:early，combine，full，interval，by

stages

remissionconsolidationmaintenanceinduction

1011～1012106～8104（MRD）

preventCNSleukemia

6cycles 3～5yearsReduceMRDstepbystepKeeptheDFSforlongtime2026/1/1546xieYi,HuaShanHospital（1）remission

inductionRegimenforALL

VP VCR1～2mg(classical) NS20cc Vqw Prednisone20~30mg/dp.ouseittillCRwouldbemoreeffective,but

relapseeasily2026/1/1547xieYi,HuaShanHospitalInductionremissionRegimenforALL

1)VDLPVCR1～2mg＋NS20ccVqw(1,8,15,21d)DNR30～40mgVgttqd1～3d,15～17d

Pred40mg～60mgp.o1～14dL-ASP10,000u

Vgtt19－28d2026/1/1548xieYi,HuaShanHospital

2)VP160.2Vgttqd×3d

Ara-C0.1～0.15Vgttqd×7dMTX2～3gVgtt

24hafter12h,leucovorin

6～9mgmq8h×2dhydrotherapy&alkalize

leukemiainCNScouldbetreatedInductionremissionRegimenforALL2026/1/1549xieYi,HuaShanHospitalInductionremissionRegimenforANLLHOAP(classical)

VCR1～2mgV

harringtonine

1～4mgVgttqd×5－7dAra－C50－100mgVgttBid×5－7dPrednisone30－60mgp.oqd×5－7d

interval14d2026/1/1550xieYi,HuaShanHospital

InductionremissionRegimenforANLLHA

harringtonine2-4mgVgtt×7Ara-C0.1～0.2Vgtt×7HDAra-CAra-C2.0Vgttq12h×3DADNR30~40mgVgtt×3Ara-C0.1～0.2Vgtt×72026/1/1551xieYi,HuaShanHospital

InductionremissionRegimenforANLLPML(M3):retinoidacid(ATRA)60－80mgp.oUsechemotherapyinconsolidationstageWhenrelapse:As2O35mgVgtt×28dHypoplasticleukemia

Ara-C12.5mgMqd×21d

harringtonine

1mgMqd×21d2026/1/1552xieYi,HuaShanHospitalCR

therearenotanemiafeverhemorrhageandinfiltrationHb>100g/LWBC<10×109/LPLT>100×109/LBM:blasts<5%2026/1/1553xieYi,HuaShanHospital（2）Theregimen

inconsolidationremissionstageUsingainductionremissionregimenforsixcycleszUsingdifferentinductionremissionregimenalternatelyforsixcycles2026/1/1554xieYi,HuaShanHospital（3）maintenanceremission

regimentreatmentwithextendedintervalusingthedifferentinductionremissionregimenalternatelyfor3~5YinintervaltimethepatientswithALLwilltakeCTX，6-MP，6-TG&

MTX,P.ONotmaintaintherapyunlessleukemiarelapseProtectthecapacityofbodyimmunity,improvequalityoflife2026/1/1555xieYi,HuaShanHospital

supportivecare

conponenttransfusiontherapyRBC

,rhEPOplateletantibiotics（倒階梯）,IVIG,rhG-CSFVeinhighnutrition

protectheart,liver&kidney2026/1/1556xieYi,HuaShanHospital

othersTherapeuticLeukapheresisTotreattheLeukostasis(WBC>105)TopreventtumorlysissyndromeimmunotherapymonoantibodytoCD33+drug2026/1/1557xieYi,HuaShanHospital

othersHemapoieticstemcelltransplantation

CouldbecurableExpensiveandhighriskAcutemyelomonocyticleukemia

withDICUsethelowmolecularheparintoimproveprognosis2026/1/1558xieYi,HuaShanHospital

CNSleukemiaIncidenceofALL

10－40%，ANLL2－4%Couldbefoundinyouthage，whosufferedfrominfiltration,

easilyonsetinremissionstagealways2026/1/1559xieYi,HuaShanHospital

Theclinicalmanifestation&diagnosisofCNSleukemia

Clinicalexamination

IntracranialhypertensionThesignsofmeningesstimulated

thesignsofnervesinjureCSFexamination

presure>200mmH20,sugar

，protein（>40mg/dl),WBC>10/mm3couldfind

leukemiacells

2026/1/1560xieYi,HuaShanHospital

ThetreatmentofCNSleukemia

HighdoseMTXinjectionMTX5－10mgsheathenjectionBiw－qw(dilutionwithinjectionwater3ml,add.dexamethasome

5mg)2.4Gy

60Coradiationtohead2026/1/1561xieYi,HuaShanHospital

ThepreventionofCNSleukemia

AfterCRMTX5－10mgsheathrejectionqw×6IncidenceofCNS

leukemia,<5%2026/1/1562xieYi,HuaShanHospitalChronicMyelogenousLeukemia(CML)aClonalproliferativedisorderofpluripotentstemcellConsistentlyassociatedwiththePhchromosomeandBCR-ABLfusiongeneAbout15~25%ofallcasesofleukemia25~60years,slightlymoreinmenthanwomen

2026/1/1563xieYi,HuaShanHospital9ABL

q34

q11BCR22

q34Ph

q11

t(9;22)(q34;q11)MECHANISM—PhCHROMOSONE2026/1/1564xieYi,HuaShanHospital

BCR2

ABLBCR-ABLFusiongene8.5KbmRNA(b3a2orb2a2)210Kdprotein(P210)

7.5kb

mRNA

(b1a2)→190Kd(p190)→Ph(+)ALL1231MECHANISM—PhCHROMOSONECML2026/1/1565xieYi,HuaShanHospital

CMLdevelopmentInitialindolentchronicphase(CML-CP,3~4years)isfollowedbyacceleratedphase(CML-AP)andblastphase(CML-BP,asacuteleukemia)2026/1/1566xieYi,HuaShanHospitalClinicalmanifestationWeightloss、fatigue,excessivesweatingsternaltenderness,splenomegalyWBC

>200×109/L,Leukostasis(白細(xì)胞淤滯)

2026/1/1567xieYi,HuaShanHospitalWBC10～1000×109/L

Granulocytesatallstagesofdevelopmentarepresentinblood（幼粒細(xì)胞血癥）

orPLT>1000×109/L

oranemiaNAP(neutrophilalkalinephosphataseactivity)＝0BMproliferate

，Granulopoiesisisdominent.blast<10%，B&

E

ph1(+)

90%;

pcr,BCR/ABLfusiongene(+)Clinicalmanifestation2026/1/1568xieYi,HuaShanHospital

CML:diagnosis

SymptomsarevagueandnonspecificSplenomagly,90%;sternaltenderness

WBC10～1000×109/L

Granulocytesatallstagesofdevelopmentarepresentinblood,

NAP＝0BMproliferate

,Granulopoiesisisdominentblast<10%，B&

E

andErythropoiesis

megakaryocytopeoiesis

andreticulinfibrosis

ph1(+),bcr-abl(+)2026/1/1569xieYi,HuaShanHospitalCMLbystagesChronicphaseaccelerativephas

blastphase

Asymptomatic,anemia,hemorrhage,likeasacutesplenomegalysplenomegalyleukemia

eosinophiliabasophiliccell

basophlia>20%

blastblast

blast

<10%10~20%>20%

PLT<100×109/L

>1000×109/L2026/1/1570xieYi,HuaShanHospital

CML:differentiationdiagnosis

1、leukemoidreaction：infection,canceretc

WBC

,thereisn’tsplenomegalyNAP

，absenceofBlast,ph1,bcr～abl2、myelofibrosis：WBC

&Splenomegalyteardroppoikilocytes,nuclearedredcellinblood

BM:aspirationisoftenunsuccessful;NAP

，absenceofBlast,ph1

and

bcr～abl;

biopsy：collagenfibrosis2026/1/1571xieYi,HuaShanHospital

CML:differentiationdiagnosis3、acuteleukemia

ph1

in

2%AML

ph1

in

5~25%ALL4、acuteabdomenAbsenceofsplenomegalyandthefricativeinlefthypochondrialregion

2026/1/1572xieYi,HuaShanHospital

CML:treatment1,keepWBC4.0～10.0×109/L(1)

Hydroxyurea(羥基脲)0.5～2.0tid

Busulfan(馬利蘭)1～10mgqd當(dāng)歸蘆薈丸→青黛→靛玉紅→甲異靛