LUKEMIA

Golden rules in science & medicine:• Start strong stay strong ; start loose become more loose• Look for fundamentals & let the details look for themselves ( so, after study of each subject do a subject skeleton /mind map for it )

• Truly, one picture is worth ,at least, a thousand words.• Do not rush in your diagnosis.• Common is common.

Golden rules in genetics:• Each human character is controlled by

2 genes / gene clusters on 2 homologous chromosomes so, gene is the unit of inheritance. • Each specific gene encodes for a specific antigen or protein.

HEMATOLOGICAL MALIGNANCIES

Hematological Malignancies

Definition:-Group of haematological disorders characterized by

clonal expansion of

haemopoietic cells which has undergone

genetic mutation

Haemopoietic cells :in the marrow or peripheral lymphoid tissue

Clonal :derived from a single cell proliferation ( N.B. it is autonomous & uncontrolled) compare with normal haemopoiesis

Clonal evolution of malignancy

Most malignancies r the result of several sequentially acquired mutations rather than single catastrophic mutation.

Stromal cells are the major source of growth factors except for:

a. Erythropoietin, 90 % of which is synthesized in the kidney. b. Thrombopoietin, made largely in the liver.

POINTS OF INTEREST IN NORMAL HEMOPOIESIS

CDK

p53 is known as the ‘ guardian of the genome ‘

Cell cycle

The genes involved in the development of Haematological malignancies

can be broadly divided into 2 groups:

1. Oncogenes 2. anti-oncogenes / Tumour Suppressor Genes (TSG)

OncogenesOncogenes Tumour Suppressor Genes (TSG)

(anti-oncogenes)

proto-oncogenes

are often involved in

transduction ( transfer of external signals to the nucleus to activate genes )

TSG act in Cell cycle control (Checkpoint)

( G-1 S G-2 M )DNA damage cell-cycle arrest for 1 of 2

1.DNA repair & continuation of cell cycle2.Apoptosis by activating pro-apoptotic genes

Oncogenes arise because of

gain-of-function mutation in the normal cellular genes

( proto-oncogenes )

TSG may acquire

loss-of-function mutation malignant transformatione.g. p53 (at 17p13 ) & Rb (at 13q14 )

One of the striking features of haemat.malign. ( in contrast to most solid tumours ) is

high frequency of translocations ( t )

Usually point mutation or gene deletion (del.)

Examples of chromosomal translocations in haematological malignancies

will be mentioned later on

p53 the { guardian of the genome } is

The most significant TSG in human cancer

It is mutated or inactivated in > 50 % of malignant diseases including

many haematological malignancies

The aetiology of Haematological Malignancies

It is a combination of genetic background & environmental influence that determines the risk of

developing haematological malignancy

I. Inherited factors :- see next page

II. Environmental influence: #. Chemicals #. Drugs #. Radiation #. Infections

I. Inherited factorsI. Inherited factors

The incidence of leukaemia is greatly increased in some genetic diseases , particularly :

D W - F A B

D Down’s syndrome:

20-30-fold increased frequency of AL ( M-7)W Wiskott - Aldrich syndrome ( WAS ):

F Fanconi’s anaemia 10% of cases develop AML A Ataxia telangiectasia B Bloom’s syndrome Ashkenazi Jewish with TID Telangiectasia + life-threatening infections + dwarfism

Autosomal recessive characterized by :

•Defective DNA repair &•Hypersensitivity to other DNA damaging agents

X-linked recessive ( Thrombocytopenia & BLEEDING with small plt & defective plt. Aggr. + recurrent infections-due to COMBINED IMMUNE-PARESIS in infancy)

Tri-somy-21

#. Chemicals : chronic exposure to benzene may cause #. Chemicals : chronic exposure to benzene may cause BM hypoplasia , dysplasia & chromosomal BM hypoplasia , dysplasia & chromosomal

abnormalities abnormalities & is unusual cause of MDS or AML& is unusual cause of MDS or AML #. Drugs : The alkylating agent (e.g. chlorambucil ; Melphalan) #. Drugs : The alkylating agent (e.g. chlorambucil ; Melphalan)

predispose to AML,predispose to AML, especially if combined with radiotherapy especially if combined with radiotherapy or if used to treat patients with or if used to treat patients with lymphocytic or plasmacytic lymphocytic or plasmacytic

disordersdisorders

#. Radiation : Radiation ,especially to the BM, is leukaemogenic #. Radiation : Radiation ,especially to the BM, is leukaemogenic see fig.-- see fig.--

#. Infections: Pls, refer to lymphoma Fig.10-2#. Infections: Pls, refer to lymphoma Fig.10-2

II. Environmental influence II. Environmental influence

Alkylating agent express reactive alkyl group

which make covalent bond with cell molecules (particularly purine in DNA) DNA damage

The most commonSpecific abnormalityin childhood ALL is thet ( 12 ; 21 )

HAEMOPOIETICSTEM CELLS

(HSC)(CD34+ ; CD38-)

LYMPHOID STEM CELLS

MYELOID STEM CELLS

LYMPHOCYTES OTHER BLOOD CELLS


(HSC)

LYMPHOID STEM CELLS

MYELOID STEM CELLS

LYMPHOCYTES RBCOTHERWBC

PLATELET


LYMPHOID STEM cell

MYELOID STEM CELLS

LYMPHOCYTES

ACUTECHRONIC

OTHER BLOOD CELLS

ACUTE

CHRONIC

HSC or early progenitors

Maturing & mature cells

usually aggressive & rapidly fatal if not rapidly treated

x x

some has high cure rate e.g. ALL( L1) in children

X


LYMPHOID STEM CELL

Lymphoblast

MYELOID STEM CELL

Myeloblast

LYMPHOCYTES

ACUTE

CHRONIC

MYELOID

LYMPHOID

OTHER BLOOD CELLS

Lymphoblasts

Lymphocytes Granulocytes

Myeloblasts

ALL AML

CMLCLL

LYMPHOID STEM CELLS

Pre-T

Thymocyte

Peripheral T Cells

T-Helper

T-Supp.

Pro-B

Pre-B

B- Virgin

B- Mature

LPC

PLASMACELL

ALL

CLL

MYELOIDSTEM CELLS

PRO-NORMOBLAST

RBC

MONO-BLAST

MONO-CYTE

MYELOBLAST

PRO-MYELOCYTE

MYELOCYTE

META-MYELOCYTE

BAND or STAB

GRANULOCYTES

MEGA-KARYO-BLAST

PLATELET

AMLCML

Acute Leukemia means

Maturation Arrest

Sustained SELF-RENEWALat the expense of

DIFFERENTIATION

accumulation of BLAST CELLS

Differentiation (Maturation)

Self-renewal

Maturation Arrest

Sustained self-renewal

Differentiation (Maturation)

AcuteLeukemia

Normal

ACUTE LEUKEMIASTypes&

Sub-types

INCIDENCE

Age

Clinical presentation & Lab. Data

B.M. failure Anaemiasymptoms & signs of anaemia

Neutropenia recurrent infections NB Total WBC count( High; Normal or low )

Thrombocytopenia bleeding tendency

Tissue Infiltration


Anaemiasymptoms & signs of anaemia

Neutropenia recurrent infections


Tissue Infiltration: e.g. organomegaly (hepatosplenomegaly) ; lymphadenopathy ; meningeal syndrome( headache, nausea, vomiting, blurring of vision & diplopia with blast cells in CSF) ; skin lesions ; testicular swelling -------- etc.

B.M. failure caused byaccumulation of

BLAST cells

ALL AML

TYPES & AGE mainly children

~ 4 yr

mainly adults

ALL the most common malignancy of childhood

( 25-30 % )

a second rise

after the age of 40 yr

AML incidence increase with age

LAB DIAGNOSIS OF ACUTE LEUKAEMIA

• Complete Blood Count (CBC) & smear

• BM aspiration & trephine BiopsyBM aspiration & trephine Biopsy

• Special (cyto-chemical) StainsSpecial (cyto-chemical) Stains

• Immunological markers Immunological markers (Immuno-pheno-type “ IPT”) by (Immuno-pheno-type “ IPT”) by Flow cyto metry “FCM”Flow cyto metry “FCM”

• Chromosomal studiesChromosomal studies

• Cyto-genetic analysisCyto-genetic analysis• Molecular genetic analysis including FISHMolecular genetic analysis including FISH

• Storage of BM smears wrapped in aluminum foil at -20˚CStorage of BM smears wrapped in aluminum foil at -20˚C

• Others: microbiological ; Biochemical .........etc. Others: microbiological ; Biochemical .........etc.

CBC ;Smear & BM aspiration

Acute Leukaemia (AL) is defined as the presence of over 20 % of blast cells in the peripheral blood or bone marrowat clinical presentation

Q: Could we diagnose AL with less than 20 % blasts ?A: YES , if specific leukaemia-associated cytogenetic or molecular genetics abnormalities are present

AML

FAB SUB-TYPES OF AL

M0

M1

M2

M3M4

M5

M6

M7L1

L2

L3

ALL

Morphological classification of AL

Burkitt’s Lymphoma is the Lymphomatous correlate of L- 3 ALL

LYMPHOBLASTS IN ALL FAB SUBTYPES

L1 L2 L3small & monomorphic

é large N/C ratio

Larger& heterogeneousé more abundant Cy.

& more prominent Ni.

large & homogeneous

é marked Cy. basophilia &

Cy. vacuoles

ACUTE LEUKEMIAS SPECIAL STAINS

M1-M4

M5

L2 LYMPHOBLAST

MYELOBLAST

MONOBLAST

PASPeriodic acid- Schiff

*Sudan Black-B’SBB’*Myeloperoxidase’MPO’

*Specific Esterase

Non-Specific Esterase

IPT of AL

Pro-B common Pre-B

CD 10 ( CALLA )

- ++

±

often infant

Commonly child

cIg +ve

malepredominance &Mediastinalmass

B-ALL

sIg +v e

CD14&CD15: M4 & M5Glycophorin -A : M6CD41a(GpIIb/IIIa) : M7

CD 14 & !% in M4& M5Glycophorin A in M6CD41a in(

Myeloperoxidae in M0CD14 &CD15 in M4 & M5Glycophorin-A in M6CD41a in M7

TdT ; Terminal deoxynucleotidyl transferase

~12%

L1 or L2

~ 3%

L3

~85%

L1 or L2

Prognostic factors in ALLPrognostic factors in ALL

Good PoorAge Child Adult ( or infant < 2

yr )

Sex Girls boys (?) testes is a common site for relapse

CNS disease at presentation

( - ) ( + )

WBC count Low High (> 50.000 /µL)

IPT CALLA T-ALL ( in children )

Cytogenetics Normal or Hyperdiploid

Ph + ve , or Pseudo-diploid

Time to clear blasts from blood

< 1 week > 1 week

Time to remission

< 4 week > 4 week

Minimal residual disease (MRD)

(- ve) at 1-3 months

( still + ve) at 3 - 6 months

MyeloblastM0-M1

MonoblastM5

Pro-normoblast

Megakaryo -blast

M7

Promyelocyte

M3

AMLFAB-sub-types M0 - M7

M2

M4

M6

N.B. odd No.:- single cell even No.:- double cell

Auer rods

M5a(monoblastic)

M5b(monocytic)

Pro-normoblast

M7Megakaryo -

blastic

M3 Ac. Promyelocytic L.

(APL)

AMLFAB-sub-types

M2

with

gran

ulo

cytic

matu

ration

M4 with granulocytic & monocytic

maturation

M6 ( Erythroleukaemia)

N.B. odd No.:- single cell even No.:- double cell

M0undifferentiated

M1 without maturation

M5Megakaryo-

blast

M7

Promyelocyte

M3 & M-3v

AMLSpecific clinical. features

M4 tissue infiltration

Acute MF(no splenomegaly BM MK—blasts)

DD:- MMMMyelofibrosis éMyeloid Metaplasia DIC

ACUTE LEUKEMIAS SPECIAL STAINS

M4

M5

MYELOBLAST

MONOBLAST

*Sudan Black-B’SBB’*Myeloperoxidase’MPO’

*Specific Esterase

Non-Specific Esterase

DE

M2-SBB+ve Auer rod M2-SBB+ve CG

M2-MPO+ve CG

M4-SBB+ve My

Mo-ve

AML é.out

Maturation M1 M2 AML égranulocytic Maturation

Myeloblast

Promyelocyte

C: Heavy azurophilic granulation

(hypergranular) & Auer rods (rod-shaped granules) strongly positive for MPO

Faggot cells : cells with bundles of Auer rods

N: with nucleoli (Ni)

APL M3Classical

APL APL M3

Faggot cell

APLAPL(M-3v) micro-granular (M-3v) micro-granular variantvariant

Characterized by: paucity of myeloid granules & dumb-bell nucleus

M-3v

AML (AMML)

M4 AML with granulocytic & monocytic maturation

Monoblast Myeloblast+

Myeloblast

Pro-normoblast

> 50% of the nucleated marrow cells r

erythroid &Myeloblasts < 30% BM NEC

M6AMLErythroleukemia

M6

Myeloblast

Megakaryo-blast

Large and small megakaryoblasts with high N/C ratio

C: is pale & agranular with blebs

EM Platelets Peroxidase +ve

AML

M7

Megakaryoblastic L.

IPT of AL

Pro-B common Pre-B

CD 10 ( CALLA )

- ++

±

often infant

Commonly child

cIg +ve

malepredominance &Mediastinalmass B-ALL

sIg +v e

CD14&CD15: M4 & M5Glycophorin -A : M6CD41a(GpIIb/IIIa) : M7

CD 14 & !% in M4& M5Glycophorin A in M6CD41a in(

Myeloperoxidae in M0CD14 &CD15 in M4 & M5Glycophorin-A in M6CD41a in M7

TdT; Terminal deoxynucleotidyl transferase

~12%

L1 or L2

~ 3%

L3

~85%

L1 or L2

M5t ( 9 ; 11 )

t ( 11 ; 19 )del (11q)

M3 t ( 15 ; 17 )

AML Translocations (t) & other chromosomal changes

M2

t ( 8 ; 21 )

M4-Eo inv ( 16 ) del ( 16q )

11q23 abnormalities

detected in 85 % of secondary AML

Prognostic factors in AMLPrognostic factors in AML Good Poor

Age Aged 40-60 yr induction remission 80%

Adult ( >60 yr ) or (infant < 2 yr )

Previous MDS / MPD / Chemotherapy

( - ) i.e. denovo ( + )

CML-BC lymphoid myeloidCNS or extra med. Disease at presentation

( - ) ( + )

WBC count Low High (> 50.000 µL)

Trilineage Dysplasia ( - ) ( + )

IPT ( CD-34 ; HLA-DR & TdT ) ( - ve ) ( + ve )

Translocations t(8,21) ; t(15,17) & inv(16)

del ( 5 or7 ) ; ( 11q23 )

Complete remission

after 1 course ?

Yes No

Multi-drug resistance

(MDR) ( - ) ( + )

Hybrid Acute Leukaemia (Hybrid Hybrid Acute Leukaemia (Hybrid AL)AL)

AL with blast cells showingAL with blast cells showing

features of both ALL & AMLfeatures of both ALL & AML

Bi-phenotypic

Bi-lineal

Blasts

with features of ALL

Blasts with features of both ALL & AML on

the same cell

Blasts

with features of AML

2 separate cell populations

Up to 1993,the reported

cases are 160

The 1st reported case in Arab countries

AML is the type often found inCong. Leukaemiaparticularly M5&M7

Prognosis is extremely poor

The Practitioner.Vol.10,No12,Dec.1999





Tissue Infiltration: e.g. organomegaly (hepatosplenomegaly) ; lymphadenopathy ; meningeal syndrome( headache, nausea, vomiting, blurring of vision & diplopia with blast cells in CSF) ; skin lesions ; testicular swelling -------- etc.

B.M. failure caused byaccumulation of

BLAST cells

PallorPallor

InfectionInfectionss

Pneumonia

Bleeding Tendenc

y

Extensive BruisingMucosal Bleeding

Purpura

Bleeding TendencyBleeding Tendency

Retina

Cerebral

Lymphadenopathy

Gum Hypertrophy

Leukemic Skin Infiltrate

Testicular Leukemia

Leukemic Infiltrate

Mediastinal InvolvementMediastinal Involvement

Therapy of ALTherapy of AL

Supportive: for BM failureSupportive: for BM failure

Specific: Chemotherapy Specific: Chemotherapy ± Radiotherapy± Radiotherapy

*. Induction of remission*. Induction of remission

*. Intensification (consolidation)*. Intensification (consolidation)

*. Cranial prophylaxis*. Cranial prophylaxis

*. Maintenance therapy*. Maintenance therapy

Stem Cell Transplantation: allogeneic SCTStem Cell Transplantation: allogeneic SCT

Myelodysplasia of

Haemopoietic cells

Ineffective Haemopoiesis




Myelodysplastic Syndrome Myelodysplastic Syndrome (MDS)(MDS)

ANT in various combinations : RA : Refractory anaemia RN : Refractory Neutropenia RT : Refractory Thrombocytopenia R Bicytopenia : ( e.g. A + N ; A + T ; N + T etc.---------------)

M D SM D SPB BM

Refractory anaemia ( RA )

Blasts < 1 % Blasts < 5 %

RA withring sideroblast( RARS )

Blasts < 1 %

Blasts < 5 %Ring sideroblasts

> 15 % of total erythroblasts

RA with excess blasts( RAEB )

Blasts < 5 % Blasts 5 - 20 %

RAEB in transformation( RAEB-t )

Blasts >5 % Blasts over 20 %or Auer rods present

Chronic myelo-monocytic leuk.

( CMML ) 20% of MDSTissue infiltr.( gum hypertrophy; splenomeg.; skin rash & LAP)

As any of the above with

Persistent monocytosis

> 1.0 X 10 3/ µL

Any of the above with

Promonocytes

LOW

RISK

HIGH

RISK

ChronicLymphocyticLeukaemia

(CLL)

Chronic Myeloid

Leukaemia(CML)

TYPES & AGE

Peak incidence

70 ± 10 yr Male : female 2 : 1

Any age but most frequently at the age of

50 ± 10 yr Male : female 1.4 : 1

Only 15 %before the age of 50 yr

Chronic

Myeloid

Leukaemia

(CML)


High total WBC count : 50 – 500 X 10 3 / µLHyper-Leucocytosis

*..In up to 50 % of casesDx. is made incidentally from the routine CBC

bleeding tendencyinspite thrombocytosis(?)Plt.dysfunction

Clinical Presentation of CML

Huge spleenDiscomfort& Indigestion (small meals)

Hyper-metabolism: #.weight loss #. Lassitude #.night sweat #.anorexia (?) mimic hyper-thyroidism

Gout &Renal impairment

Visual disturbances & Priapism 2ry to hyperleucocytosis & leuco-stasis with impaired microcirculation

Urticaria

AnaemiaNormocyticNormochromic

High total WBC count e.g. 50 - 500X10 3 / µLHyper-Leucocytosis

Smear: complete spectrumof myeloid cells (myeloblast in the chronic phase: less than 5 %)with eosinophilia & basophilia

#. Most frequent thrombocytosis but, may be normal or low#. Plt.dysfunction

Laboratory features of CML

• Ph’ pos.: over 95 % NB: Ph’ neg. BCR-ABL pos. CML behaves clinically like Ph’ pos. CML

• Hyperuricaemia• High B12& B12 binding capacity (due to increased TC-1 from neutrophil)• False hyperkalaemia

(K+ released from leucocytes) &false hypoglycemia ( glucose consumed by leucocytes)

• Low NAP score ( N :20-100 ) (neutrophil alkaline phosphatase)

BM: Hypercellular with granulocytic predominance

RaisedRaised LowLow

PPolymorphnuclear Leucocytosis olymorphnuclear Leucocytosis

( Myeloid Leukaemoid ( Myeloid Leukaemoid Reaction ;Reaction ;

Neutrophilia ;Neutrophilia ;

Neutrophil leucocytosis)Neutrophil leucocytosis)

MyeloMyelopproliferative Disorders roliferative Disorders (MPD)(MPD) - - Polycythaemia (rubra) vera - PRVPolycythaemia (rubra) vera - PRV

- Myelofibrosis ( MF )- Myelofibrosis ( MF )

PPregnancyregnancy

NAP score

CML

The Philadelphia ( Ph’ ) chromosome: reciprocal translocation

BCR-ABL oncoprotein :

210 KDa in CML & some Ph’+ve ALL due to M-BCR: Major-BCR 190 KDa in other Ph’+ve ALL due to m-BCR: minor-BCR

BCR-ABL = Breakpoint Cluster Region- Abelson Leukaemia

Chronic Myeloid Leukaemias (CML)Chronic Myeloid Leukaemias (CML)

CML , Ph + ( CGL- CML , Ph + ( CGL- Chronic Granulocytic LeukaemiaChronic Granulocytic Leukaemia)) CML , Ph – ( atypical ) CML , Ph – ( atypical ) <5% poor prognosis<5% poor prognosis Juvenile myelomonocytic leukaemiaJuvenile myelomonocytic leukaemia (Juvenile (Juvenile

CML)CML)

Chronic neutrophilic leukaemiaChronic neutrophilic leukaemia Eosinophilic leukaemiaEosinophilic leukaemia Chronic myelomonocytic leukaemia (CMMLChronic myelomonocytic leukaemia (CMML))

refer to refer to Myelodysplastic Syndrome Myelodysplastic Syndrome

(MDS)(MDS)

ChronicPhase

AcceleratedPhase

CML

BlastCrisis

( 70 % of CML )

BLAST CELLSBLAST CELLS

less than less than

5 %5 % more than more than

20 %20 %inbetween

Glivec is the first line drug in the management of CML-chronic phaseComplete haematological response in virtually all patients ,

but the aim of treatment is Complete cytogenetic response { (-) Ph’ chromosome in BM in cytogenetic analysis }

Juvenile CMLJuvenile CML

Young Children (1st 4 yr of life) boys: girls (2:1) Tissue infiltrations ( Skin rash ; HSM & LAP ) Blasts & promonocytes < 20% in PB & BM Monocytosis >1X103/µL hence, the name JMML No BCR-ABL fusion gene Hb-F high for age (a useful diagnostic feature) Poor prognosis (if untreated BC& death usually occur within 4 yr)

Treatment of choice is SCT

Juvenile myelo-monocytic leukaemia (JMML)

Chronic LymphocyticLeukaemia(s)

*. B-Chronic Lymphocytic Leukaemia ( CLL ) The most common of Chronic Lymphoid Leukaemias

ChronicLymphocyticLeukaemia

(CLL)

Chronic Myeloid

Leukaemia(CML)

TYPES & AGE

Peak incidence

70 ± 10 yr

Any age but most frequently at the age of

50 ± 10 yr only 15 %before the age of 50 yr

Male : female 2 : 1

Male : female 1.4 : 1

Chronic Lymphocytic Leukaemia (CLL)Chronic Lymphocytic Leukaemia (CLL)

Etiology : Etiology : UnUnknownknown No higher incidence after chemo-therapy or radio-No higher incidence after chemo-therapy or radio-

therapytherapy ( in contrast to( in contrast to CML: CML: incresed incidence in survivors of atom bomb in Japan)incresed incidence in survivors of atom bomb in Japan)

The most common leukaemia in the western worldThe most common leukaemia in the western world ( ( ?? due to increased routine medical check-up ) due to increased routine medical check-up ) 77 fold increased risk of CLL in fold increased risk of CLL in the close relativesthe close relatives of the patient of the patient

CLLCLL is characterized by proliferation and accumulation of is characterized by proliferation and accumulation of

mature-lookingmature-looking but but bbiologically immature iologically immature B lymphocytesB lymphocytes ( ( weak surface expression of Ig-M & Ig-Dweak surface expression of Ig-M & Ig-D ). ). #. Accumulation ; where & why ?#. Accumulation ; where & why ? PB ; BM ; LN ; liver & spleenPB ; BM ; LN ; liver & spleen as a result of impaired apoptosis i.e. elderly lymphocytesas a result of impaired apoptosis i.e. elderly lymphocytes

Early:

Bacterial infections

Advanced Disease:

viral & fungal infections

Immunosuppression is significant Due to:

1. Hypo- gamma- globulin- aemia

2. Cellular immune dysfunction

Anaemia: Hb < 10 g/dL

Thrombocytopenia: Plt < 100 x10 3 / µL

Lymphadenopathy Symmetrical ; discrete & not tender (cervical ; axillary or inguinal) The most frequent clinical sign

Hepatosplenomegaly

Absolute Lymphocytosis ( > 5x103/µL & sustained ) most cases Dx in routine CBC

Stage III : As stage 0 + Anaemia (Hb < 10 g/dL)

± Adenopathy ± Organomegaly

Stage IV: As stage 0 + Thrombocytopenia (Plt < 100 x 10 3 / µL) ± Adenopathy ± Organomegaly

Stage I : As stage 0 + Adeno-pathy

Stage II:

Stage 0: Absolute Lymphocytosis

As stage 0

+ Organomegaly ( Enlarged liver & / or spleen)

± Adeno-pathy

Rai classification of CLL

Early:

Bacterial infections

Advanced Disease: viral & fungal infections reduced S. Ig conc.

Anaemia Hb < 10 g/dL normocytic &normochromic

Thrombocytopenia: Plt < 100 x10 3 / µL

Lymphocytosis (5-300 x103/µL)

Smear: 70-99% small mature-looking lymphocytes with smudge (smear) cells

BM aspiration : Lymphocytic replacement of normal marrow elements Lymphocytes comprise 60 ± 35 %

Lab. Dx

Causes of anemia in CLLCauses of anemia in CLL

Primary( Marrow Infiltration )

Hyper-splenism Immune

Chemotherapy

FolateDeficiency

Elderly NutritionalDeficiency

SECONDARY

Causes of thrombocytopenia in Causes of thrombocytopenia in CLLCLL

Primary( Marrow Infiltration )

Hyper-splenism Immune

Chemotherapy

SECONDARY

The most common The most common Chromosomal Abnormalities in CLLChromosomal Abnormalities in CLL

Deletion 11q23Trisomy 12

Deletion 17pinvolving the p53

deletion 13q14 good prognosis

Bad prognosis

Bilateral inguinal lymphadenopathy

Gross enlargement of the lymph nodes inboth axillary regions in a 70-year-old female

Richter’s Syndrome (Large cell transformation)

(Immuno- blastic transformation)

5 % of CLL with fever & weight loss

Large blast cell (previously termed Immuno-

blast) spillover to the blood with monoclonal protein in

serum & free light chain in urine

BM & LN examination reveals the same cells

( Large cell lymphoma)

PBS showing large blast cells (immunoblasts)

LUKEMIA

Education

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