再生障礙性貧血（英文版）

AplasticanemiaCONTENTSINTRODUCTIONETIOLOGY/PATHOGENESISMANIFESTATIONSLABORATORYFINDINGSDIAGNOSIS&DIFFERENTIALTREATMENTAplasticanemia(AA)DefinitionAA,anunusualhematologicdisease,istheparadigmofthehumanbonemarrowfailuresyndromes.

-marrowhypoplasia

-peripheralpancytopeniaIncidence:7.4permillionpopulation

East>West

Biphasicpeakat20-25and>60yCauses:Inherited(20%)FanconianemiaDyskeratosiscongenitaCartilagehairhypoplasiaPearsonsyndromeAmegakaryocyticthrombocytopeniaShwachman-DiamondsyndromeDubowitzsyndromeDiamond-BlackfansyndromeFamilialaplasticanemiaCauses:Acquired(80%)

Infections:hepatitis,EBV,HIV,parvovirusRadiationandchemicalssuchasbenzeneDrugs:chloramphenicol,phenylbutazone,goldPNH

(paroxysmalnocturnalhemoglobinuria)TransfusionalgraftversushostdiseaseLivertransplantationPregnancyPathogenesisDepletionofhemopoieticstemcellSuppressionofproliferationandmaturation

Mechanism

-Immunerelated

-CytotoxicT-cell,INF(Interferon)γ,TNF(tumornecrosisfactor

)α↑PresentationAnemia:pallor,headache,palpitations,

dyspnea,heartfailureThrombocytopenia:mucosalandgingival

bleedingorpetechiaNeutropenia:infections,mouthand

pharyngealulcerationsTestsPB,BM(multiple)smear,biopsy,cytochemistryChromosomeTcellnumberandfunctionOthers

VirusAb(hepatitis,herpes,rubella…)

Coombstest(direct&indirect)

VitB12

ANA(antinuclearantibody),C3,C4

Hbelectrophoresis,

sugarwatertest

HLAtyping,BMchromosomeBMaspirationandbiopsyDIAGNOSISOFAACriteria

directevidencesexclusiveevidencesSubtypes

SAA(severeAA)

VSAA(verysevereAA)NSAA(notsevereAA)CRITERIAOFAADIRECTEVIDENCES:PancytopeniaHypocellularityofBM3myeloidlineagesobviouslyreducedinBMIncreasedpercentagesandfunctionofTlymphocytesNormalmorphologicshapesofPBandBMcellsCRITERIAOFAAEXCLUSIVEEVIDENCES:NoevidenceofmalignanciesNoinfitrationevidenceNomonoclonalevidenceNoevidenceofPNHNoevidenceofPNHRBCNodeficiencyofGPI-anchor-proteinNosoonerresponsetoprednisoneCRITERIAOFAAEXCLUSIVEEVIDENCES:NoevidenceofFANoFAfamilyhistoryNoFAchromosomefeatureNoevidenceofEvanssyndrome

&otherIRP(immunerelatedpancytopenia)Noauto-AbmediateddiseaseNoauto-AbsagainstRBC,BPC&BMCNoextravascularhemolysisNosoonerresponsetoprednisoneCRITERIAOFAAEXCLUSIVEEVIDENCES:NomalnutritionevidenceFolicacidand/orvitaminB12OthernutritionelementsNoendocrinediseaseevidenceNoevidenceoftemporaryfailureofhematopoiesisSUBTYPESOFAASAAPB:severepancytopeniaRC<15.0

109/L

NC<0.5

109/L

PC<20.0

109/LBM:widelyhypocellularIliac,SternalBMcellularity<25%SUBTYPESOFAAVSAA:OnekindofSAAPB:veryseverepancytopeniaNC<0.2

109/LOtherssameasthoseofSAABM:sameasSAANSAAAllAAcasesexceptSAAIn“CAA

(chronicAA)”categoryMortality/MorbidityPancytopenia:infectionandbleeding

Mortality>70%inSAAwithsupportivecarealone

BMTorimmunetherapy:drugtoxin,GVHD,otherclonaldiseases(MDS,PNH……)TREATMENTOFAATreatmentforsymptomsTreatmentforpathogenesisSYMPTOMATICTREATMENTOFAAOBJECTIVETorescuepatientsfromthefatalcomplicationsTomaintainpatient’slifeforrecoveryofhemopoiesisTocreatechancesforpathogenictreatmentSYMPTOMATICTREATMENTOFAATHERAPIESTherapiesofbleedingTherapiesofinfectionTherapiesofsevereanemiaTherapiesofothercomplicationsSYMPTOMATICTREATMENTOFAATHERAPIESOFBLEEDINGPlatelettransfusionEpinephrinelikehemostatsSupplementofcoagulationfactorsAnti-fibrinolysisOthersSYMPTOMATICTREATMENTOFAATHERAPIESOFINFECTIONByexperiences

BysensitivitytestsHGFs:G-CSF(300ug/d,H)IVIg:2.5g~5.0g/dOthersupportivetherapiesProphylactictherapiesSYMPTOMATICTREATMENTOFAATHERAPIESOFSEVEREANEMIARBCtrasfusionSAA:maintainHb70~80g/LNSAA:maintainHb50~60g/LAAwithsevereinfectionIronchelationtherapySYMPTOMATICTREATMENTOFAATHERAPIESOFOTHERCOMPLICATIONSHeartdisease:heartprotectionLiverdisease:lipidplusamino

acidkidneydisease:reducedCSADiabetes:reducedprednisoneDisbalanceofinnerenvironment:supplyingdifficientelementsTREATMENTFORPATHOGENESISOFAAIMMUNOSUPPRESSIONHEMOPOIETICSTIMULATINGSTEMCELLTRANSPLANTATION

IMMUNOSUPPRESSIONTHERAPIESOFAACORTICOSTEROIDSATG

(antithymocyteglobulin)/ALG(antilymphocyteglobulin)MONOCLONEAb:CD3CSAHD-IVIgCTX(cyclophosphamide)ATG/ALG+CSA(Immunosuppressivetherapy,IST)Immunosuppressivetherapy5yearsurvival:60-80%(Bacigalupoetal,2000)

Indication:1.Nomatchdonor2.SAA3.Age>35-40yearsoldImmunosuppressivetherapyATGLysislymphocyteCyclosporinBlockTcellfunctionATG+CSA

(betterthanATGorcyclosporinalone)Response>3monthsLong-termfollowupRelapse(10%)Laterclonaldisease:PNH,MDS,AMLHEMOPOIETICSTIMULATINGINAAAndrogenFolicAcid

andVitB12HGFsG-CSF

300ug/dGM-CSFsamedosageaboveEPO

(erythropoietin)6000ug/dIL11(interleukin-11),TPO

(thrombopoietin)?STEMCELLTRANSPLANTATIONBMTwithAidentical

twindonorALLO-BMTOtherSCTsinAAwerefewReasons:Age,costs,donorHLA-identicaltransplantation75~90%longtermcureGVHD:acute18%chronic26%Indication:1.SAAorVSAA2.Age<30~40yearsoldHLA:hi