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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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Reaching the diagnosis of acute leukemiaReaching the diagnosis of acute leukemia
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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Investigations of acute leukemiaInvestigations of acute leukemia
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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Investigations of acute leukemiaInvestigations of acute leukemia
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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Reaching the diagnosis of acute leukemiaReaching the diagnosis of acute leukemia
Is it acute leukemia?myeloid or lymphoblastic?
What is the FAB classification?
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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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Bone marrow aspiration cytologyBone marrow aspiration cytologyAML or ALL?AML or ALL?
ii- Cytochemistry :
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+(coarse)
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ALL
+
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-
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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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Bone marrow aspiration cytologyBone marrow aspiration cytologyAML or ALL?AML or ALL?
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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Reaching the diagnosis of acute leukemiaReaching the diagnosis of acute leukemia
Is it acute leukemia?Is it acute leukemia?myeloid or lymphoblasticmyeloid or lymphoblastic?
What is the FAB classification?
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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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M3-Promyelocytic leukemiaM3-Promyelocytic leukemia
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M3-Promyelocytic leukemiaM3-Promyelocytic leukemia
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M3-Promyelocytic leukemiaM3-Promyelocytic leukemia
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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Management of Acute LeukemiaManagement of Acute Leukemia
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
Management of Acute LeukemiaManagement of Acute Leukemia
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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CML- InvestigationsCML- Investigations
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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CML- InvestigationsCML- Investigations
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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CML- InvestigationsCML- Investigations
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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CML- InvestigationsCML- Investigations
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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CML- InvestigationsCML- Investigations
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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Management of Chronic CMLManagement of Chronic CML
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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Management of Chronic CMLManagement of Chronic CML
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
-
8/14/2019 Leukaemias for Fifth Year
93/112
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
-
8/14/2019 Leukaemias for Fifth Year
94/112
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
-
8/14/2019 Leukaemias for Fifth Year
95/112
CLLCLL
-
8/14/2019 Leukaemias for Fifth Year
96/112
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
-
8/14/2019 Leukaemias for Fifth Year
97/112
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
-
8/14/2019 Leukaemias for Fifth Year
98/112
enlarged lymphatic tissueenlarged lymphatic tissue
InfectionInfection
-
8/14/2019 Leukaemias for Fifth Year
99/112
herpes zoster herpes zoster
CLLCLL
-
8/14/2019 Leukaemias for Fifth Year
100/112
investigationsinvestigations
CBCCBCPBFPBF
BM aspirationBM aspirationImmunochemistryImmunochemistryTotal protein and Ig levelTotal protein and Ig level
CLLCLL
-
8/14/2019 Leukaemias for Fifth Year
101/112
CBCCBCPBFBM aspirationimmunochemistry
Total protein and Ig level
investigationsinvestigations
-
8/14/2019 Leukaemias for Fifth Year
102/112
CLLCLL
-
8/14/2019 Leukaemias for Fifth Year
103/112
CBCPBFPBFBM aspirationImmunochemistry
Total protein and Ig level
investigationsinvestigations
P i h l bl d filPerioheral blood film
-
8/14/2019 Leukaemias for Fifth Year
104/112
Perioheral blood filmPerioheral blood film
PredominantlyPredominantlylymphocytosislymphocytosis
Normally lookingNormally lookingPresence of Presence of smudge cellssmudge cells
CLLCLL
-
8/14/2019 Leukaemias for Fifth Year
105/112
CBCPBFBM aspirationBM aspirationImmunochemistry
Total protein and Ig level
investigationsinvestigations
Bone marrow aspirationBone marrow aspiration
-
8/14/2019 Leukaemias for Fifth Year
106/112
Not essential for diagnosisNot essential for diagnosisInfiltration of the bone marrow byInfiltration of the bone marrow bylymphocytes.lymphocytes.
Bone marrow aspirationBone marrow aspiration
CLLCLL
-
8/14/2019 Leukaemias for Fifth Year
107/112
CBCPBFBM aspirationImmuno chemistryImmuno chemistry
Total protein and Ig levelTotal protein and Ig level
investigationsinvestigations
I h i
-
8/14/2019 Leukaemias for Fifth Year
108/112
Immunoglobulin levelsImmunoglobulin levels
Low immunoglobulin levelsLow immunoglobulin levels
Immuno-chemistry
CD19 positiveCD19 positiveCD20 positiveCD20 positive
CD5 positiveCD5 positive
CLL- stagingCLL- staging
-
8/14/2019 Leukaemias for Fifth Year
109/112
CLLCLL
-
8/14/2019 Leukaemias for Fifth Year
110/112
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
-
8/14/2019 Leukaemias for Fifth Year
111/112
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
-
8/14/2019 Leukaemias for Fifth Year
112/112
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