Leukaemias for Fifth Year

8/14/2019 Leukaemias for Fifth Year

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LeukaemiasLeukaemias

A group of disorders characterized by theA group of disorders characterized by theaccumulation of abnormal white cells in theaccumulation of abnormal white cells in thebone marrowbone marrow


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LEUKAEMIASLEUKAEMIAS

Accumulation of abnormal white cells in the bone marrowCapable of further division

Bone Marrow Failure Circulating WBC Organ infiltration

Anaemia

NeutropeniaThrombocytopenia

Liver Spleen

Lymph NodesMeninges

BrainSkin

TestisGums


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Acute LeukemiasAcute Leukemias


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Acute LeukaemiasAcute LeukaemiasEpidemiology:Epidemiology:

Not a common diseaseNot a common disease50% of all leukaemias50% of all leukaemias

ALLALLCommonst leukaemia in childrenCommonst leukaemia in childrenAge 3-4 yrs and > 40 yrsAge 3-4 yrs and > 40 yrs

AMLAMLCommonst acute leukemia in adultCommonst acute leukemia in adultAny ageAny age

Males > FemalesMales > Females


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Clinical presentation of Acute LeukemiaClinical presentation of Acute LeukemiaA- due to bone marrow failureA- due to bone marrow failure

Anaemia:Anaemia:Pallor, fatigue, exertional dyspnea, palpitaionPallor, fatigue, exertional dyspnea, palpitaion

NeutropeniaNeutropenia infection:infection:Sore throat, malaise, fever, skin and perianal or respiratory infection, septicaemiaSore throat, malaise, fever, skin and perianal or respiratory infection, septicaemiaThrombocytopenia:]Thrombocytopenia:]

Spontaneous bruises, purpura, bleeding gums, menorrhagia, bleeding from punctureSpontaneous bruises, purpura, bleeding gums, menorrhagia, bleeding from puncturesitessites

DIC in AML (M3)DIC in AML (M3) life threatening bleedinglife threatenin g bleeding

B- due to organ infiltration:B- due to o rgan infiltration:ALLALL

Bony tenderness and joint painBony tenderness and joint painSuperficial lymphadenopathySuperficial lymphadenopathyHepato-spleenomegalyHepato-spleenomegalyMeningeal involvementMeningeal involvement

Testicular involvementTesticular involvementMediastinal disease(T-Cell)Mediastinal disease(T-Cell)AMLAML

HepatosplenomegalyHepatosplenomegalyGum hypertrophy(M5)Gum hypertrophy(M5)Skin infiltration (M5)Skin infiltration (M5)Meningeal involvemnt (M4,M5): headache, nausea, vomitting, convulsions,Meningeal involvemnt (M4,M5): headache, nausea, vomitting, convulsions,papilloesemapapilloesema


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Clinical features of acute leukemiaClinical features of acute leukemia

AnemiaAnemia


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Clinical features of acute leukemiaClinical features of acute leukemia

Infection due to neutropeniaInfection due to neutropenia


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Clinical presentation of acute leukemiaClinical presentation of acute leukemia

BleedingBleedingdue to thrombocytopenia or DIC(AML-M3)due to thrombocytopenia or DIC(AML-M3)


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InvestigationsInvestigations

Aim:Confirm diagnosisAssess patients performanceAssess complications


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Reaching the diagnosis of acute leukemiaReaching the diagnosis of acute leukemia

Is it acute leukemia?Is it acute leukemia?myeloid or lymphoblastic?myeloid or lymphoblastic?

What is the FAB classification?What is the FAB classification?


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Laboratory InvestigationsLaboratory Investigations

Full Blood CountsFull Blood Counts

Blood film:Blood film:Bone marrow aspiration cytologyBone marrow aspiration cytologyFlow cytometryFlow cytometry

CytogeneticsCytogeneticsothersothers


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Is it acute leukemia?Is it acute leukemia?myeloid or lymphoblastic?

What is the FAB classification?


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Investigations of acute leukemiaInvestigations of acute leukemia

a- Full blood counta- Full blood countHbHb

Anaemia:Anaemia:Normocytic or macrocyticNormocytic or macrocytic

WBC:WBC:normal, high up to 200 x10normal, high up to 200 x10 99 /l/lor low (aleukaemicor low (aleukaemicleukaemia)leukaemia)

PlateletsPlatelets

Thrombocytopenia:Thrombocytopenia:more sever in AMLmore sever in AML nemianemia

ESRESR


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b- peripheral blood smear b- peripheral blood smear

MyeloblastsModerat to largeAbundant cytoplasmGranules in cytoplasmAurs rods> 2 nucleoli

LymphoblastsSmall to moderateScanty cytoplasmNo cytoplasmic granules1-2 nucleoli


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c- bone marrow examinationc- bone marrow examination

Bone marrowBone marrowaspiration cytology:aspiration cytology:

Hyper cellular boneHyper cellular bone

marrowmarrowBlast cells >30%

Dry tap : in ALL some times

it is difficult to aspirate themarrow due to presence of reticulin fibres


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Is it acute leukemia?myeloid or lymphoblastic?



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Bone marrow aspiration cytologyBone marrow aspiration cytologyAML or ALL?AML or ALL?

i- morphology:i- morphology:MyeloblastsMyeloblastsModerat to largeModerat to largeAbundant cytoplasmAbundant cytoplasmGranules in cytoplasmGranules in cytoplasmAurs rodsAurs rods> 2 nucleoli> 2 nucleoli

LymphoblastsSmall to moderateScanty cytoplasmNo cytoplasmic granules1-2 nucleoli


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ii- Cytochemistry :

-

-

+(coarse)

-

-

ALL

+

-

-

-

-

T-ALL

-Acid phosphatase

+(M4,M5)

Non-specific esterase

+(fine , except M6 )

PAS

+Sudan Black

+Myeloperoxidase

AML


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Myeloperoxidase positivityMyeloperoxidase positivity

AML


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Sudan Black and ChloroacetateSudan Black and Chloroacetateesterase positivityesterase positivity

AML

B i ti t l gB i ti t l g


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iii- Immuno-chemistry :

-+(M7)CD41

-+CD33

-+CD13+-CD22

+ (T-ALL)-CD7

+-CD19

+-CD10

+-TdT

ALLAML


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ALL-Indirect immune-flourescencestaining for tdt usingflourescin labellingand CD10 antigen usingavidin labelling

AML-M7CD41 positive


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d- flow cytometryd- flow cytometry

ALLCD10 positive

ALLCD34 positive


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Is it acute leukemia?Is it acute leukemia?myeloid or lymphoblasticmyeloid or lymphoblastic?



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AML- FAB classificationAML- FAB classification

M0M0 minimal differentiationminimal differentiationM1M1 AML without maturationAML without maturationM2M2 AML with granulocytic maturationAML with granulocytic maturationM3M3 promylocyticpromylocyticM4M4 myelomonocyticmyelomonocyticM5M5 monocyticmonocytic

M6M6 erythroleukemiaerythroleukemiaM7M7 megakaryocyticmegakaryocytic


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M0M0

Large, agranular blasts.Large, agranular blasts.

Myeloperoxidase negative or


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M1- myeloblastic leukemia withoutM1- myeloblastic leukemia withoutmaturationmaturation

Cells show some granulocytic differentiation.Cells show some granulocytic differentiation.3% or more of blasts are myeloperoxidase positive3% or more of blasts are myeloperoxidase positiveBlasts contain few azurophilic granules, Auer rods or both.Blasts contain few azurophilic granules, Auer rods or both.Further maturation not seen.Further maturation not seen.


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M2- myeloblastic leukemia withM2- myeloblastic leukemia withmaturationmaturation

Presence of maturation at or beyond the promyelocyte stage.Cells are nucleated and have varying amounts of cytoplasm, usuallywith many azurophilic granulesAuer rodsMyelocytes,metamylocytes and mature granulocytes may be found

t(8;21) is frequently associated with M2.


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AML-M2AML-M2

AML-M2 myeloperoxidase

AML-M2 sudan black AML-M2 t(8;21)


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M3-Promyelocytic leukemiaM3-Promyelocytic leukemia

Most of cells are abnormal promyelocytes with heavy granulation.Nucleus vary greatly in size and shape, it is often reniform or bilobed.DICt(15;17) are invariable


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Typical bilobed nuclei seen in M3 variant. The basophilicTypical bilobed nuclei seen in M3 variant. The basophiliccytoplasm is packed with granules too small to resolve by lightcytoplasm is packed with granules too small to resolve by lightmicroscopy, but which give the typical cytochemical reactions of microscopy, but which give the typical cytochemical reactions of

M3M3


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M4-Myelomonocytic leukemiaM4-Myelomonocytic leukemia


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AML-M4AML-M4


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M5- monocytic leukemiaM5- monocytic leukemia


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AML-M5AML-M5

Large monoblasts with central nuclei and abundant cytoplasm.Large monoblasts with central nuclei and abundant cytoplasm.The inset shows the monoblasts positive with alpha-napthylThe inset shows the monoblasts positive with alpha-napthylacetate esterase (brown), and one blue chloroacetate esteraseacetate esterase (brown), and one blue chloroacetate esterase

positive myelocyte.positive myelocyte.


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AML-M6AML-M6

AML M6


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AML-M6AML-M6

Giant multinucleate late normoblasts (left). Granular Giant multinucleate late normoblasts (left). Granular PAS positivity in proerythroblasts and homogeneousPAS positivity in proerythroblasts and homogeneous

positivity in the later normoblasts.positivity in the later normoblasts.


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AML-M6AML-M6PASPAS


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M7M7


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M7M7


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AML-M7AML-M7

Trephine biopsy showing fibrosis, blast cells andTrephine biopsy showing fibrosis, blast cells andatypical small megakaryocytes.atypical small megakaryocytes.


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FAB classification of ALLFAB classification of ALL

L1L1 small, scanty cytoplasm, cytoplasmicsmall, scanty cytoplasm, cytoplasmiceosimophilia and vaculations are minimaleosimophilia and vaculations are minimal

L2L2 in betweenin betweenL3L3 moderate, moderate cytoplasm, markedmoderate, moderate cytoplasm, markedcytoplasmic vaculations and basophilia,cytoplasmic vaculations and basophilia,prominent neucleoliprominent neucleoli


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ALL-L1ALL-L1

small,

scanty cytoplasm,

cytoplasmiceosimophilia

vaculations areminimal


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ALL-L2ALL-L2


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L3L3

moderate cytoplasm,

marked cytoplasmicvaculations

basophilia,

prominent neucleoli


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Classification of acute leukemaiaClassification of acute leukemaia

Acute lymphoblastic leukemiaAcute lymphoblastic leukemia

Common type pre-BCommon type pre-B

70%70%

T-cellT-cellB-cellB-cellundifferentiatedundifferentiated


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ALLALLcommon-ALLcommon-ALL


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ALLALLT-ALL subtypeT-ALL subtype


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Management of Acute LeukemiaManagement of Acute Leukemia

A- Supportive:A- Supportive:Correct anaemia:Correct anaemia:

Packed cell transfusion to raise Hb level to > 10g/dlPacked cell transfusion to raise Hb level to > 10g/dlControl bleeding:Control bleeding:

Platelet transfusion if;Platelet transfusion if;

BleedingBleedingPlatelet count < 20 000/cmmPlatelet count < 20 000/cmmDIC: fresh frozen plasma + heparin + ranexemic acidDIC: fresh frozen plasma + heparin + ranexemic acid

Treat infection:Treat infection:Febrile neutropenia: a fever > 38Febrile neutropenia: a fever > 38 ooC for > 1 hour in a patient with aC for > 1 hour in a patient with aneutrophil count < 1000/cmm, it is an oncological emergency, treat withneutrophil count < 1000/cmm, it is an oncological emergency, treat withantibiotics once suspected.antibiotics once suspected.Commmon organisms:Commmon organisms:

Bacteria:specially the normal flora in throat, skin and gutBacteria:specially the normal flora in throat, skin and gutSkin: Gm+ve, staph and strepSkin: Gm+ve, staph and strepGut: gm ve, ps, areugonosa, E-Coli,and anerobesGut: gm ve, ps, areugonosa, E-Coli,and anerobes

Viral: herps virusViral: herps virusFungi: candida, aspergillusFungi: candida, aspergillusProtozoa: toxoplasmaProtozoa: toxoplasma


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Treatment of infection:Treatment of infection:Once suspected, examine patient thouroughly lookingOnce suspected, examine patient thouroughly lookingfor site of infection.for site of infection.Send cultures:Send cultures:

Blood and all suspected sourcesBlood and all suspected sourceseg, throat swab, iv catheter tip, perianal swab, etceg, throat swab, iv catheter tip, perianal swab, etc

CXR, urine, C/SCXR, urine, C/S

Start antibiotic treatment once infection is suspectedStart antibiotic treatment once infection is suspectedAminoglycosides + antipseudomonal or 3 rd generationAminoglycosides + antipseudomonal or 3 rd generationcephalosporincephalosporinIf no response after 48 hours, add an antifungalIf no response after 48 hours, add an antifungalVancomycinVancomycin infested iv catheters or once staph isinfested iv catheters or once staph is

suspectedsuspectedFluconazoleFluconazole oral and pharyngealoral and pharyngealcandidiasis#Amphotericin Bcandidiasis#Amphotericin B systemic fungal infectionsystemic fungal infectionAcyclovir Acyclovir herpes infectionherpes infection


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Supportive care, contdSupportive care, contdPrevent infection:Prevent infection:

IsolationIsolation

Decontamination of gut and skinDecontamination of gut and skinTreat hyperuricemia:Treat hyperuricemia:

AllopuranolAllopuranol

Proper hydrationProper hydrationKeep lvel < 7 mg /dlKeep lvel < 7 mg /dl


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Aim of treatmentAim of treatmentControl of BM and systemic diseaseControl of BM and systemic diseaseTreatment of sanctuary site disease CNSTreatment of sanctuary site disease CNS


Specific treatmentSpecific treatment


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ALLALL

Induction of remissionInduction of remissionPhase IPhase I

Anthracyclin + prednisolone + vincristineAnthracyclin + prednisolone + vincristineIT methotrexateIT methotrexate

Phase IIPhase II

Cyclophosphamide + cytosar + 6 mercaptopurineCyclophosphamide + cytosar + 6 mercaptopurineIntensification phaseIntensification phase

High dose methotrexateHigh dose methotrexateCranial irradiationCranial irradiation

Consolodation phaseConsolodation phaseEtoposide, vincristine, cytosar, daunorubicin, cyclophosphamide,Etoposide, vincristine, cytosar, daunorubicin, cyclophosphamide,6 thioguanine6 thioguanine

Maintenance phaseMaintenance phaseVincrisitine, prednisolone, 6mercaptopurine, methotrexate,Vincrisitine, prednisolone, 6mercaptopurine, methotrexate,interferon alfainterferon alfa


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BMT in ALLBMT in ALL

Indications:Indications:High risk ALLHigh risk ALL

Ph chromosome positive ALLPh chromosome positive ALLVery high peripheral WBC at presentationVery high peripheral WBC at presentationCD 10 patientsCD 10 patients

Relapsed ALLRelapsed ALL


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AMLAML

Phases of treatment:Phases of treatment:Induction of remissionInduction of remission

Postremission treatmentPostremission treatmentNo maintenance therepy is givenNo maintenance therepy is givenNo CNS prophylaxis is givenNo CNS prophylaxis is given

CNS disease occurs in < 5% of patientsCNS disease occurs in < 5% of patients


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AML specific treamtnetAML specific treamtnet

Induction of remission:Induction of remission:Anthracycline +Anthracycline +cytosine arabinosidecytosine arabinoside ++

6 thipguanine6 thipguanineRequire intensice supportive measuresRequire intensice supportive measuresM3M3

low dose heparinlow dose heparin

Retinoic acidRetinoic acid

Postremission treamtnentPostremission treamtnentSame regimenSame regimen


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BMT in AMLBMT in AML

Indications:Indications:High risk groupHigh risk group

Deletion of 5q and 7q, trisomy 8, t(6;9), t(9;22)Deletion of 5q and 7q, trisomy 8, t(6;9), t(9;22)History of myelodysplasiaHistory of myelodysplasia

Early first relapseEarly first relapse


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Chronic leukaemiasChronic leukaemias

Chronic myelogenousChronic myelogenousleukaemialeukaemia

Chronic lymphocytic leukaemiaChronic lymphocytic leukaemia


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Chronic leukaemiasChronic leukaemias

Chronic myelogenousChronic myelogenousleukaemialeukaemia

Chronic lymphocytic leukaemia


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Chronic myelogenous leukaemiaChronic myelogenous leukaemia

A Myeloproliferative disorder A Myeloproliferative disorder A clonal disorder where 95% of patientsA clonal disorder where 95% of patientshave a distinctive cytogenetic abnormalityhave a distinctive cytogenetic abnormalitythe Philadelphia (Ph) chromosomethe Philadelphia (Ph) chromosomeMedian age of ph+ CML is 67 yrs(30-Median age of ph+ CML is 67 yrs(30-80yrs)80yrs)Medial survival is 4-6 yrs, (range 1-10yrs)Medial survival is 4-6 yrs, (range 1-10yrs)Curative only by BMTCurative only by BMT


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Myeloproliferative disordersMyeloproliferative disorders

Chronic myelogenous leukaemiaChronic myelogenous leukaemiaPolycythemia VeraPolycythemia VeraMyelofibrosisMyelofibrosisEssential thrombocythemiaEssential thrombocythemia


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CML- SignsCML- Signs

Splenomegaly ;Splenomegaly ;mild to gross, usuallymild to gross, usuallymarkedmarked

10% have normal spleen10% have normal spleenSternal tendernessSternal tendernessSigns of anaemiaSigns of anaemia


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Philadelphia chromosomePhiladelphia chromosome

A cytogenetic abnormalityA cytogenetic abnormalityDue to reciprocal translocationDue to reciprocal translocationbetween the long arm of between the long arm of chromosomes 9(9q) andchromosomes 9(9q) and22(22q) (9:22 translocation)22(22q) (9:22 translocation)It is found in all haematopoieticIt is found in all haematopoieticprecursors of CML patients.precursors of CML patients.This result in the transfer of theThis result in the transfer of theAbelson's (abl) oncogene to anAbelson's (abl) oncogene to anarea of chromosome 22area of chromosome 22termed the break-point cluster termed the break-point cluster region (bcr)region (bcr)

This results in a fused bcr-ablThis results in a fused bcr-ablgene and production of andgene and production of andabnormal tyrosine kinasabnormal tyrosine kinasprotein.protein.This protein causes disorderedThis protein causes disorderedmyelopoiesis in CMLmyelopoiesis in CML


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CML- InvestigationsCML- Investigations

Complete blood countComplete blood countPeripheral blood film smear Peripheral blood film smear Bone marrow aspirationBone marrow aspirationSouthern Blot analysisSouthern Blot analysisPh chromosome analysisPh chromosome analysis

NAP scoreNAP scoreOthersOthers


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Complete blood countComplete blood countPeripheral blood film smear Bone marrow aspirationSouthern Blot analysisPh chromosome analysis

NAP scoreOthers


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Complete blood countComplete blood count

WBC countsWBC countsIt may reach up to 500.000/cmmIt may reach up to 500.000/cmmUsually around 150.000Usually around 150.000

AnaemiaAnaemia

Platelets N or Platelets N or


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Complete blood countPeripheral blood film smear Peripheral blood film smear Bone marrow aspirationSouthern Blot analysisPh chromosome analysis

NAP scoreOthers


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Peripheral blood film smear Peripheral blood film smear

Shift to left of myeloid series with more myelocytes in PBFShift to left of myeloid series with more myelocytes in PBFthan mature WBCsthan mature WBCs

Blast cells are < 5%Blast cells are < 5%BasophiliaBasophilia


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PBF in CMLPBF in CML


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Complete blood countPeripheral blood film smear Bone marrow aspirationBone marrow aspiration

Assess cellularityAssess cellularityAssess fibrosisAssess fibrosisCytogenetic studies for Ph chromosome analysisCytogenetic studies for Ph chromosome analysis

Southern Blot analysisNAP scoreOthers


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CML - Bone marrow aspirationCML - Bone marrow aspiration

Hyper cellular bone marrowHyper cellular bone marrowShift in the myeloid series to immature forms,Shift in the myeloid series to immature forms,this increase in number as patients progress tothis increase in number as patients progress toblastic phase of the disease.blastic phase of the disease.

Myeloblast count


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Complete blood countPeripheral blood film smear

Bone marrow aspirationSouthern Blot analysisSouthern Blot analysisNAP score

Others


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CML- Southern Blot analysisCML- Southern Blot analysis

It is a quantitative testIt is a quantitative testUsed for breakpoint cluster region geneUsed for breakpoint cluster region generearrangement.rearrangement.It may substitute bone marrow sampling toIt may substitute bone marrow sampling tomonitor response to therapy.monitor response to therapy.


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Complete blood countPeripheral blood film smear Bone marrow aspiration

Assess cellularityAssess fibrosisCytogenetic studies for Ph chromosome analysis

Southern Blot analysisNAP score LOWOthers


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CML- InvestigationsCML- InvestigationsComplete blood countPeripheral blood film smear Bone marrow aspiration

Assess cellularityAssess fibrosisCytogenetic studies for Ph chromosome analysis

Southern Blot analysisNAP score

OthersVitamin B12 level due to secretion of transcobolamin III

Uric acid


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Management of CMLManagement of CML

Types of response:Types of response:Hematological response:Hematological response:

Absence of abnormal cells in peripheral blood andAbsence of abnormal cells in peripheral blood andbone marrow.bone marrow.

Cytogenetic response:Cytogenetic response:

Absence of philadelphia chromosome positivityAbsence of philadelphia chromosome positivityand abl-bcr geneand abl-bcr gene

f


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Management of Chronic CMLManagement of Chronic CML

Allogenic BMTAllogenic BMTIs the only curative treatment available of Is the only curative treatment available of CML so far CML so far

It should be considered in the first year of It should be considered in the first year of diagnosis if the patient is


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GleevecGleevec (Imatinib mesylate)(Imatinib mesylate)A tyrosine kinase inhibitor A tyrosine kinase inhibitor Tyrosine kinase is required for transformingTyrosine kinase is required for transforming

functioin of the bcr-able fusion proteinfunctioin of the bcr-able fusion proteinIt induces hematological remission in almostIt induces hematological remission in almostall patients with interferon resistent CMLall patients with interferon resistent CML

Cytogenetic response is seen in 50% of Cytogenetic response is seen in 50% of patients.patients.

f Ch i C


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HydroxureaHydroxureaUses:Uses:

Initial treatment to lower WBC count prior to interferonInitial treatment to lower WBC count prior to interferontherapy.therapy.

Palliative treatment of patients failing other treatment.Palliative treatment of patients failing other treatment.

BusulfanBusulfanRarely usedRarely used

SplenectomySplenectomyHypersplemismHypersplemismdiscomfortdiscomfort

fA l d h f CML


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Accelerated phase of CMLAccelerated phase of CML

FeaturesFeaturesBone painBone painSpleenomegalySpleenomegaly

Resistance to current treatmentResistance to current treatmentProgressive anaemiaProgressive anaemiaThrombocytopenia or thrombocytosisThrombocytopenia or thrombocytosis

Blast cells >5% in either PB or BM and 5% in either PB or BM and


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l i h f CBl i h f CML


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Blastic phase of CMLBlastic phase of CML

FeaturesFeaturesFever Fever MalaiseMalaise

Progressive splenomgalyProgressive splenomgalyBlast cells >30% in PB or BMBlast cells >30% in PB or BM

Bl i h f CMLBl i h f CML


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Blastic phase of CMLBlastic phase of CML

TreatmentTreatmentImatinib mesylateImatinib mesylate

myeloid crisismyeloid crisis

Ph chromosome positive ALLPh chromosome positive ALLVincrisitne and prednisoloneVincrisitne and prednisolone ++ anthracyclineanthracyclineAllogenic BMTAllogenic BMT

Of benefit in


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CLLCLL


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CLLCLL

EpidemiologyEpidemiologyThe most common leukemia in adultThe most common leukemia in adultmales >femalesmales >females

> 45 yrs> 45 yrsHere mature lymphocytes fail to respond toHere mature lymphocytes fail to respond toAg stimulationAg stimulation

95% are B cell type95% are B cell type5% are T cell type5% are T cell type

The overall 5 year survival is 60%The overall 5 year survival is 60%

CLLCLLCli i l iCli i l t ti


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Clinical presentationClinical presentation

Indolent lymphocytosis (asymptomatic)Indolent lymphocytosis (asymptomatic)Generalized lymphadenopathyGeneralized lymphadenopathyHepato-splenomegalyHepato-splenomegalyPancytopeniaPancytopenia

AnaemiaAnaemiaCoombs positive hemolysisCoombs positive hemolysisHypoplasticHypoplastic

BleedingBleeding

Production thrombocytopeniaProduction thrombocytopeniaImmune thrombocytopeniaImmune thrombocytopenia

InfectionInfectionDepressed immunoglobulin levelsDepressed immunoglobulin levels

l d l h i il d l h ti ti


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enlarged lymphatic tissueenlarged lymphatic tissue

InfectionInfection


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herpes zoster herpes zoster

CLLCLL


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investigationsinvestigations

CBCCBCPBFPBF

BM aspirationBM aspirationImmunochemistryImmunochemistryTotal protein and Ig levelTotal protein and Ig level

CLLCLL


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CBCCBCPBFBM aspirationimmunochemistry

Total protein and Ig level



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CLLCLL


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CBCPBFPBFBM aspirationImmunochemistry



P i h l bl d filPerioheral blood film


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Perioheral blood filmPerioheral blood film

PredominantlyPredominantlylymphocytosislymphocytosis

Normally lookingNormally lookingPresence of Presence of smudge cellssmudge cells

CLLCLL


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CBCPBFBM aspirationBM aspirationImmunochemistry



Bone marrow aspirationBone marrow aspiration


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Not essential for diagnosisNot essential for diagnosisInfiltration of the bone marrow byInfiltration of the bone marrow bylymphocytes.lymphocytes.

Bone marrow aspirationBone marrow aspiration

CLLCLL


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CBCPBFBM aspirationImmuno chemistryImmuno chemistry

Total protein and Ig levelTotal protein and Ig level


I h i


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Immunoglobulin levelsImmunoglobulin levels

Low immunoglobulin levelsLow immunoglobulin levels

Immuno-chemistry

CD19 positiveCD19 positiveCD20 positiveCD20 positive

CD5 positiveCD5 positive

CLL- stagingCLL- staging


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CLLCLL


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whom to treat?whom to treat?Stage AStage A

Observation onlyObservation only

Stage BStage BObservation only for asymptomaticObservation only for asymptomaticChemotherapy for symptomaticChemotherapy for symptomaticlymphadenopathylymphadenopathy

Stage CStage CShould be treatedShould be treated

CLLCLL


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treatmenttreatmentSupportive treatmentSupportive treatment

Treat infectionTreat infectionHerpes zoster Herpes zoster Pseudomonas cariniiPseudomonas cariniiCandida albicansCandida albicans

Proper hydrationProper hydration ++ allopurinolallopurinolSpecially in patients with large lymph nodes (bulky disease)Specially in patients with large lymph nodes (bulky disease)to prevent tumour lysis syndrometo prevent tumour lysis syndrome

Automimmune anaemia or thrombocytopeniaAutomimmune anaemia or thrombocytopeniacorticosteroidscorticosteroids

Blood transfusionBlood transfusionHigh dose immuneglobulinHigh dose immuneglobulinCyclosporineCyclosporineSplenectomySplenectomyLow dose radiation to the spleenLow dose radiation to the spleen

CLLCLL


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Treatment optionsTreatment optionsOral alkylating agents with or without corticosteroidsOral alkylating agents with or without corticosteroidsChlorambucilChlorambucil ++ prednisoloneprednisolonePurine analogues: Fludrabine, 2-chlorodeoxyadenodinePurine analogues: Fludrabine, 2-chlorodeoxyadenodineor pentostatinor pentostatin

Better response, no advantage in survival and more side effectsBetter response, no advantage in survival and more side effects

Combination chemotherapy:Combination chemotherapy:CVP: cyclophosphamide, vincristine, prednisoloneCVP: cyclophosphamide, vincristine, prednisoloneCHOP: cyclophosphamide, doxorubicin, vincristine, prednisoloneCHOP: cyclophosphamide, doxorubicin, vincristine, prednisolone

Involved field radiotherapy: for lymph node areasInvolved field radiotherapy: for lymph node areasSplenic radiation for palliation of hypersplenismSplenic radiation for palliation of hypersplenismMonoclonal antibodies: CAMPATH-1H and rituximabMonoclonal antibodies: CAMPATH-1H and rituximabunder trialunder trialBone marrow transplantation and peripheral stem cellBone marrow transplantation and peripheral stem cell

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Leukaemias for Fifth Year