LEUKEMIA
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abnormal, uncontrolled proliferation and accumulation of more than 1 hematopoietic cell; major signs are fever, weight
loss, increased sweating
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WBC normal value 4.5-11.5 x 109 L; RBC4.5-6.5 x 1012 L; Platelets 150-450 x 109 / L
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a generalized neoplastic proliferation or accumulation of leukopoietic cells
a condition in which there is a growth of tissue that serves no physiological function
with or without the involvement of peripheral blood
INFILTRATION of NON - hematopoietic cells
CLASSIFICATION:
Classified regarding lineage and cell maturity 4 broad categories
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Acute Myeloid Leukemia (AML)
Chronic Myeloid Leukemia (CML)
Acute Lymphoblastic Leukemia (ALL)
Chronic Lymphocytic Leukemia (CLL)
ACCORDING TO ONSET
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Acute leukemia
✓ if no remission, it is fatal within 3 months
✓ Bone Marrow is packed with primitive cells
✓ Young cells are seen in the bone marrow (blast)
Subacute leukemia
✓ involves a longer natural history of 3 - 12 months cells have intermediate differentiation
✓ There are some cells with differentiation
Chronic leukemia
✓ survival is for more than 1-year cell types are more differentiated
✓ Cell counts are many
ACUTE VS. CHRONIC LEUKEMIA (TABULAR LEUKEMIA)
ACCORDING TO CYTOLOGICAL CHARACTERISTICS MYELOID (TABULAR)
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Organ involvement mostly in chronic leukemia
ACCORDING TO CYTOLOGICAL CHARACTERISTICS LYMPHOID
Lymphoblastic Leukemia (ALL) CLINICAL FEATURES
Acute Myeloid Leukemia (AML) VS. Acute Lymphoblastic Leukemia (ALL) BLAST
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AML nucleoli( 2 or more) and ALL( 2 or less)
LEUKEMIA
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Problem: Abnormal proliferation of stem cells (variable presentation, Leukocytosis, abnormal circulating cells,
proliferation of tissue)
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Etiology: not completely understood(radiation, chemicals,virus and genetic disposition)MYELOID
MYELOID DISORDERS
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Comprise a group of closely related syndromes characterized by self - perpetuating proliferation
of Bone marrow cells
Cells involved: Erythroid precursors, Granulocytes, Monocytes, Megakaryocytes
proliferation is the ABNORMAL cause is UNKNOWN
ALL cell line or a SINGLE cell line predominates(M3)
Common Manifestation: Fever, malaise
ACUTE MYELOID LEUKEMIA (AML) LEUKEMIA (AML)
CLINICAL FEATURES:
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childhood & adolescent: RARE
middle & later years: FREQUENT (MOST COMMON FORM OF ACUTE LEUKEMIA)
onset resembles an acute infection or a septic condition
granulocytic insufficiency w/ ulceration of mucous membranes (mouth & throat)
fever, marked prostration (loss of strength), general malaise
Initial Assessment: 500 cell count
DIAGNOSIS:
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More than or equal to (>) 20% of the nucleated cells are blast and/or leukemic cells
Usually affected are promyelocyte and promonocyte
Distinct in AML: Auer Rods (cytoplasm; elongated and large crystalline) and Phi bodies
CLASSIFICATION
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French-American-British (FAB) Cooperative Group (1976)
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Morphology of cells in Romanowsky-stained blood and marrow films
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Cytochemical reactions or serum lysozyme levels
World Health Organization (WHO) (2001) (CURRENT)
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Multilayered approach define morphology, cytogenetics, immunophenotyping
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BASIS
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Recurrent Acquired Cytogenic Abnormalities
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History of Predisposing Factors/Multilineage AML
✓ Prior to cytotoxic therapy (CHEMOTHERAPY)
✓ Prior MDS (Myelodysplastic syndrome)
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Morphologic Stratification (FAB) otherwise categorized
AML with Recurrent Genetic Abnormalities
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Affects children and young adults
Involvement of a committed precursor
High rate of complete remission (good response) with chemotherapy
Formation of fusion gene - CHIMERIC PROTEIN (protein not present in the cell types in the body)
Example:
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AML with t(8:21) –1/3 of M2 cases( children and young adults; Myeloblast with dysplastic granular cytoplasm,
Auer rods, hypo granulation, Pseudo-Pelger-Huët)
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AML with invert (16) –M4 (younger children, extramedullary disease)
Acute Promyelocytic Leukemia with t(15:17) – affect specific cell line(promyelocyte) causing hyper granularity
and Auer rods; Release of primary granules of promyelocyte causes DIC; good prognosis
AML with 11q23 abnormalities
AML with Multilineage Dysplasia
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Arise from Myelodysplastic Syndrome (MDS) or arise de novo but with features of MDS
occur in older people and poor prognosis (pancytopenia, hyper/hypo granular, Pseudo-Pelger-Huët cells)
> 20% blasts in blood and/or marrow
Dysplasia in >50% of cells of at least 2 lineages, Therapy Related
AML, Therapy Related
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Alkylating Agent - Related AML
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Chlorambucil, Cyclophosphamide or radiation
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Occur 5-10 years after exposure
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Poor response to therapy
Topoisomerase II Inhibitor - Related AML
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After 1-5 years of exposure
AML Not Otherwise Classified
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FAB Classification
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based on morphology and cytochemical reaction
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requires presence of > 20% blasts in the blood and/or marrow
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¼ of the AML cases are under this classification
FAB CLASSIFICATION
FAB CLASSIFICATION
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M0 Acute myeloblastic leukemia, minimally differentiated
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CLASSIFICATION
Common myeloblst
≥ 20% ALL NUCLEATED CELLS (ANC) are blasts
< 3% of blasts are Myeloperoxidase and SBB positive
≥ 20% of blasts are positive for myeloid-associated antigens (CD13 specific for myeloblast, CD33, CD117)
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M1 Acute myeloblastic leukemia, without maturation
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≥ 20% ANC are blasts
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≥ 90% of (non-erythroid cells) NEC are myeloblasts
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≤ 10% of leukocytes show maturation
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≥ 3% of blasts are positive for peroxidase and SBB
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Positive for chloroacetate esterase
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M1 is similar to L2 hence, cytochemical differentiation is important
M2 Acute myeloblastic leukemia, with maturation
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≥ 20% ANC are myeloblasts
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≥ 10% NEC are promyelocytes or more mature granulocytes
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< 20% are of monocytic lineage
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Myeloblast represents 20% to 89% of total marrow cells
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Usually, > 85% of leukemic cells are positive for peroxidase, SBB and Chloroacetate Esterase (CAE)
M3 Acute Promyelocytic Leukemia
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> 20% blasts and abnormal granular Promyelocytes
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Auer rods and faggot cells (promyelocytes with a cluster of Auer rods in the cytoplasm)
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Usually,>85% of leukemic cells are positive for SBB/MPX/CAE
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Translocation of 15 and 17 affecting Retinoic Acid Receptor Alpha (RARA) gene is affected
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Associated with DIC
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Common in Males
M4 Acute myelomonocytic leukemia
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AKA Naegili’s type of Leukemia
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Inversion 16
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≥ 20% of ANC are myeloblast
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Granulocytic series represent 30-80% of NEC
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sum of monoblasts, promonocytes and monocytes is
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more than 20%
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less than 80% of NECs
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≥ 20% of blasts are positive for SBB/PX/CAE/PAS
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positive for aNAE and aNBE
M4e Acute Myelomonocytic Leukemia with Eosinophilia
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Presence of eosinophilia
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Large basophilic granules mixed with smaller eosinophilic granules
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There is inversion or dilution of the long arm of chromosome 16
M5a Acute monoblastic leukemia, poorly differentiated
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AKA Schilling’s Type of Leukemia
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Translocation in 9 and 11(mostly affected)
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> 80% of NEC are monoblasts, promonocytes or monocyteS
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Negative for SBB/MPO and specific esterase
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Strongly positive for nonspecific esterase
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Highest incidence of organ involvement
M5b Acute monoblastic leukemia, differentiated
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> 80% of NEC are monoblasts, promonocytes or monocytes
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< 80% of monocytic cells are monoblasts
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Negative for SBB/MP and specific esterase
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Strongly positive for nonspecific esterase
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Reduced number of monoblast
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Associated with diffused erythematous rashes
M6 Erythroleukemia
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> 50% of ANC are erythroblasts
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AKA Di Guglielmo syndrome or Erythema Myelosis
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Many erythroid precursors are PAS-positive
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Affects Chromosome 5 and 7
M7 Acute Megakaryoblastic Leukemia
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> 20% of NEC are megakaryoblasts or leukemic cells
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platelet peroxidase positive on electron microscopy
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positive for glycoproteins Ib or IIb/IIIa
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Positive for ANAE but negative with ANBE
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Affects Chromosome 21(cytopenia and thrombosis)
CHEMOTHERAPY
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Phases( AML and ALL treatment are similar except M3)
1. Induction of Complete Remission
2. Consolidation
3. Maintenance Remission
REMISSION INDUCTION
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Goal: get rid of all visible leukemia
Drugs:
1. Cytosine arabinoside (ara-C)
2. Anthracycline (Daunorubicin)
3. Amsacrine( Resistant AML)
Administered in a week
Requires hospitalization
Target: <5% blast in the marrow after 1-2 week (40- 80% success rate)
CONSOLIDATION THERAPY
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Goal: destroy any remaining leukemia cells and prevent relapse
High dose Cytarabine in 5 days
15-40% success rate
STEM CELL TRANSPLANT
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After successful induction
1. Allogenic
2. Autologous
Factors considered
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More intensive induction
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Availability of tissue match
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Presence of 1 or more adverse prognostic factors (ex. prior MDS)
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Young patients
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Patient’s wish