White Blood Cell Neoplastic Disorders PDF

Preview

Summary

The following lecture material examines white blood cell neoplastic disorders, such as Leukemia (Acute myeloid leukemia AML, Acute Lymphoblastic Leukemia ALL )by including clinical features, general lab investigation, and treatment....

Description

White Blood Cell Neoplastic Disorders  Leukemias Bone marrow, blood, blast cells – Acute/Chronic & Myeloid/Lymphoid – AML / ALL & CML / CLL  Lymphomas – Lymph nodes, tumor – Hodgkins – Non-Hodgkins. Myeloma  Premalignant conditions: – Myeloproliferative syndromes (MPS) – Myelodysplastic syndromes (MDS)  Leukaemias are a very heterogeneous group of diseases, which differ from each other in aetiology, pathogenesis, prognosis and responsiveness to treatment  The nature of leukaemia – Leukaemia is a disease resulting from the neoplastic proliferation of haemopoietic or lymphoid cells. It results from mutation of a single stem cell, the progeny of which form a clone of leukaemic cells Leukemia Definition: Neoplastic clonal expansion of blood cells with their split in blood and tissues

BM

Blood

Tissues

Classification of Leukemia  Acute versus chronic – Cell maturity 

Acute: clonal proliferation of immature hematopoietic cells (the formation of blood or blood cells )



Chronic: mature forms of WBC; onset is more gradual

– Nature of disease onset  Type of white blood cell (WBC) – Acute lymphocytic leukemia (ALL) – Acute myelogenous leukemia (AML) Also called acute nonlymphoblastic leukemia (ANLL) – Chronic myelogenous leukemia (CML) – Chronic lymphocytic leukemia (CLL)

Leukemia- Etiology and Pathology  No single causative agent  Most from a combination of factors – Genetic and environmental influences – Chemical agents – Chemotherapeutic agents – Viruses – Radiation – Immunologic deficiencies

General Clinical Features  BM infiltration triad: anemia, bleeding, infections

 Tissue infiltration: spleen, liver, CNS,  Metabolic effects: catabolism (wt loss, hyperuricaemia. (gout). hyponatraemia ,hypokalaemia  viscosity : stasis, thrombosis, CNS,DIC General lab Investigations  CBC: low HB% & plt, BF: blasts  BM: Essential, type and percentage of blasts (20%).  Cytochemical studies: special stains  Immunophenotyping : Cell markers (CDs)  Cytogenetics: chr. Studies  Molecular biology : PCR  Other tests: biochemical: Neutrophil alkaline phosphatase, uric acid Treatment of Leukemia  Supportive – Blood transfusion – Antibiotics – Plt transfusion – Education, general hygiene.  Definitive: – Chemotherapy – BMT – Gene therapy

The Acute Leukaemias What is acute Leukemia  The acute leukemia’s are a heterogeneous group of malignant disorders, which are characterized by the uncontrolled clonal proliferation and accumulation of poorly differentiated blast cells in the bone marrow and other tissues.  Thus replacement of normal bone marrow elements with abnormal (neoplastic) blood cells.  These leukaemic cells are frequently (but not always) present in the peripheral blood stream. Subsequently there is a raised total blood count and evidence of bone marrow failure (i.e. anaemia, neutoropenia, thrombocytopenia) are ensues.  In the acute leukaemias the blasts commonly invade reticuloendothelial tissues including the spleen, liver and lymph nodes. They may also invade other tissues, infiltrating any organ of the body.  If left untreated, leukaemia eventually causes death. Acute Myeloid Leukemia (AML) Malignant clonal proliferation of myeloid (Non lymphoid) series. Classification (FAB):- French, America, and Britain  Morphological according to the stage of differentiation and maturation of myeloid series. 8 types M0: no differentiation M1- M5 myeloid diff M6: Erythroid M7 : Megakariocytic

Acute Non-Lymphoblastic Leukaemia Diagnosis

Alternative

M0

Bone Marrow Appearance Identified by ultrastructural myeloperoxidase activity or immunophenotyping.

M1

AML without maturation

Monomorphic with one or more distinct nucleoli, occasional auer rod and at least 3% myeloperoxidase positivity.

M2

AML with maturation

50% OR > myeloblasts & promyelocytes and common single auer rod. Dysplastic myeloid differentiation may also be present.

M3

APL

Dominant cell type is promyelocyte with heavy azurophilic granulation. Bundles of Auer rods confirm diagnosis. Microgranular variant exist (M3v)

M4

AMMoL

As M2 but > 20% promonocytes & monocytes.

M5

AMoL

> 80% monoblasts is poorly differentiated (M5a) > 80% monoblasts, promonocytes or monocytes is well differentiated (m5b)

M6

AEL

>50% bizzar, dysplastic nucleated red cells with multinucleate forms and cytoplasmic bridging. Myeloblasts usually > 30%.

M7

AMegL

Fibrosis, heterogeneous blasts population with cytoplasmic blebs. Platelet peroxidase positive.

Clinical Features  Of leukemia: any age, < children.  Specific features: –

usually no lymph node enlargement, little spleen

– M3 (promyelocytic) : DIC – M4-M5 ( monocytic) : tissue infiltration ( CNS, gum hypertrophy, chloroma) – M7 : down syndrome. AML

Lab Diagnosis CBC: WBC, myeloblasts with Auer rods. BM: myeloblasts> 20% Cytochemical : +ve Sudan black, Myelo pyroxidase. Cell markers: +ve CD13, 33, 67. Cytogenetics: t( 15-17), t(18-21) Genetic studies: PML-RARA gene.

Other biochemical tests: uric acid ,liver ffunction test,…. Treatment  Supportive: need more care.  Chemotherapy :4 stages: 1. Induction of remission 2. Consolidation 3. CNS prophylaxis 4. Maintenance 5. bone marrow transplantation, Gene therapy Acute Lymphoblastic Leukemia (ALL)  More commn than AML  Bimodal age : children > adults. Classification:  FAB ( morphology)

L1, L2, L3

 WHO ( immunological) B: CALL , pre B, nul ALL. B All T : FAB characterization of ALL  L1: Homogenous population of small lymphoblasts with scanty cytoplasm and scanty nucleoli. Nucleus occasionally cleft.  L2: Heterogeneous population of large lymphoblasts with moderately abundant cytoplasm & or more nucleoli. Nucleus commonly intended or cleft.

 L3-Burkitt’s type: Homogenous population of large lymphoblasts with prominent nucleoli & deeply basophilic, vacuolated cytoplasm. Clinical Features  Of leukemia +LN , spleen, testes, gout)...  Prognostic factors 1. Age : < 4----10< 2. Sex : male bad 3. WBCs > 50.000 4. Subtypes : T, Nul, L3 5. Additional chromosomal abn 6. CNS inf Lab diagnosis and TTT  CBC: lymphoblast  BM: lymphoblast > 20%  Cytochemical: +ve PAS, acid phosphatase in TALL  Markers (v.imp) CD 10,20, 19,..  Molecular biology and cytogenetic Treatment same steps as AML ,diff drugs Distinguishing AML from ALL  light microscopy – AML: Auer rods, cytoplasmic granules – ALL: no Auer rods or granules.  flow cytometry

 special stains (cytochemistry)  Cytogenetics Classification of the immature cells involved may be done by: 1- Morphology – an experienced morphologist can look at the size of the blast, the amount of cytoplasm, the nuclear chromatin pattern, the presence of nucleoli and the presence of auer rods (are a pink staining, splinter shaped inclusion due to a rod shaped alignment of primary granules found only in myeloproliferative processes) to identify the blast type: 2- The cytochemistry ALL

AML

Myeloperoxidase

-

+

Suddan Black

-

+

Non specific esterase M5

-

+ in M4

Periodic acid schiff (PAS)

+in c-ALL

+in M6

Acid phosphatase

+in T-ALL

+in M6

3- The Immunological  Immunologic markers (immunophenotyping) – these are used mainly for lymphocytes, i.e., for determining B cell or T cell lineage. These tests rely on antibodies made against specific surface markers.

Flow Cytometer

B- cell maturation

T cell Maturation

4- Cytogenetics  Cytogenetics: studies can now be used for diagnosis and for prognosis of hematologic malignancies. – Many leukemia’s (and lymphomas) are characterized by specific chromosomal abnormalities, including specific translocations and aneuploidy. The specific type of malignancy can be identified based on the specific abnormality or translocation

Type of Chromosomal Abnormality Leukemia

FAB Type

ALL

t (9;22 )

L1,L2

Pre-B ALL

t (1;19 )

L1

B ALL

t (8;14 ) t (8;22) t (2;8 )

L3

T ALL

t (11;14)

L1,L2

AML

t (8;21)

M2

APL

t (15;17)

M3

AmoL

del/t (11)

M5

inv16,and t (16;16)

M4

t (8;16)

M6

AMMoL

AEL...