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Definition : Leukemia is a malignant disease of the hematopoietic system (blood forming cells).
Characterized by uncontrolled and abnormal proliferation of stem cells in the bone marrow.
And usually spill over into the peripheral blood.
Broad Classification
Depending on:
1. Aggressiveness of disease ; Acute Leukemias & Chronic Leukemias
Acute Leukemias
Rapid onset
Very Aggressive
Cause death in weeks or months if not treated.
Chronic Leukemias
Less aggressive
slow in onset and progression
Causes death in months to years, if not treated.
Classification of Leukaemia
Myeloid
Acute myeloid leukemia (AML)
Acute Leukemia
Unregulated and progressive proliferation with accumulation of immature, hematopoietic
precursors in the bone marrow (Blasts). The Blast count in the bone marrow is more than 20%.
Types of Blasts
Myeloblast
Lymphoblast
What are the differences between these two ?
Myeloblast Vs. Lymphoblast differences are in
Morphological features Cytoplasmic granules , Auer rods , nuclear features
Cytochemical features
Immunological features (immunophenotyping)
Morphological features
AML ALL
Myeloblast Lymphoblast
Cytoplasmic feature
Cytoplasmic + -
granules
Auer rods + -
Nuclear features
Chromatin Usually fine Condensed
Nucleolus Distinct, 2-3 1-2
Cytochemical features
Myeloperoxidase + -
Sudan Black B + -
PAS -ve or Block positive
diffuse positive
in erythroblasts (
AML M6)
FAB classification of acute Leukemias
Cytochemical stains
AML M6 (erythroleukemia)
AML M7 (megakaryoblastic)
Acute myeloid leukemia
AML
Clinical Features
Common acute leukemia of adults.
Occasionally children are affected.
Signs and symptoms due to:
Organ infiltration
Pallor
Bleeding gums
Ecchymotic patches
Infiltration of tissues/organs
gum hypertrophy
bone pain
Lymphadenopathy
AML - Prognosis
Variable
60% complete remission with chemotherapy
Only 15-30% remain disease free after 5 years.
Lab findings
AML
Laboratory features
normocytic anemia
thrombocytopenia
DIC
Successful aspiration
Blast count - > 30% of all nucleated cells (FAB criteria for diagnosis of Acute leukemia)
Lymphadenopathy
Laboratory findings
Peripheral blood
Bone marrow
ALL
ALL L1
most common in children
Best prognosis
ALL L2
Most common in adults
ALL L3
Rarest form of ALL
Occurs both in adults and children
ALL
Criteria for diagnosis
>30% blasts in the BM
ALL bone marrow biopsy
AML ALL
CHRONIC LEUKEMIAS
Insidious onset
Non specific complaints: wt loss or weakness
Accumulation of more differentiated elements
All stages of maturation present.
Predominance of more mature forms.
Progress slowly
Course of the disease in years
Types
Chronic Lymphocytic leukemia (CLL)
Chronic myeloid leukemia (CML).
Chronic myeloid leukemia
(CML)
Charachterized by:
Neoplastic growth of primarily myeloid cells in the BM.
Extreme increase in no. of leucocytes and its precursors in the peripheral blood.
CML is now considered as one of the myeloproliferative disorders.
Classification of MPD
Phases in CML
Two Phases
Chronic phase
Blast crisis phase
Chronic phase
Initially patient are in Chronic phase
Respond well to therapy
Normal health restored and maintained for years.
Eventually 75% enter blast crisis phase
Blast crisis phase
Resembles Acute myeloid leukemia clinically and hematologically.
Prognosis is poor
Management is difficult
Survival is less than 6 months.
Pathophysiology of CML
Characteristic chromosomal abnormality
= Philadelphia chromosome (Ph)
Results from a reciprocal translocation between chromosome 9 and 22, t(9;22).
Clinical features
Age: Middle age ; peak 40-50 years
Sex : equal incidence in both sexes
Onset : insidious
Symptoms and signs
Weakness, loss of stamina, fever, weight loss
Fullness in abdomen/ dragging sensation in abdomen Due to massive Splenomegaly.
Bleeding from GIT, retinal hemorrhages.
Physical examination: pallor, splenomegaly, petichiae
Laboratory findings
Peripheral blood:
WBC:
Extreme leucocytosis.
WBC count: > 1lakh/c.mm.
Mean WBC count : 2-1.5 lakh/c.mm
Morphology:
Marked shift to left
Granulocytes in all stages of maturation
(myeloblasts, promyelocytes, myelocytes, metamyelocytes, band forms and segmented forms)
Predominant cell : segmented neutrophils and Myelocytes ( myelocyte peak)
Chronic phase :
Blast count < 10%
Accelerated phase:
Blast count up to 15%
Blast crisis phase:
More than 30%
Other WBCs
Increase in
Basophils, eosinophils, monocytes
Progressive basophilia heralds blast crisis
Platelet:
> 50% cases marked thrombocytosis
Thrombocytopenia : in blast crisis phase
LAP score
Leukocyte alkaline phosphatase score:
Low or absent
Bone marrow
Hypercellular
Myeloid hyperplasia
ME ratio = 10:1 to 50:1
Erythropoiesis : decreased
Myelopoiesis: Cells in all stages of maturation
Blast less than 30% in chronic phase but > 30% in blast crisis phase
Megakaryocytes: increased in no.
Late stages : bone marrow shows fibrosis
Condition in which there is marked increase in WBC count with shift to left.
Seen in:
Infections
Inflammatory disorders
Severe hemorrhage
Hemolytic states
The peripheral smear findings resemble findings in CML.
Therefore it is important to differentiate this condition from CML.
Differences between leukemoid reaction and CML
Usually >10,000/mm3
Clinical features
Age: exclusively a disease of adults.
Indolent, often asymptomatic
Fatigue, weight loss, anorexia
Autoimmune hemolytic anemia
Lymphadenopathy
CLL - Pathophysiology
Clonal B-cell neoplasm (>95% of cases)
Express mature B-cell markers
CD19, CD20,
Closely related to small lymphocytic lymphoma
Laboratory findings
Peripheral smear: The findings are diagnostic.
RBC: Normocytic normochromic
WBC:
High count 10,000 to 1,50000/c.mm
Absolute lymphocytosis
Lymphocytes: monotonous in appearance, round nucleus, clumped chromatin and scant blue
cytoplasm.
Smudge cells : due to rupture of fragile lymphocytes.
Peripheral smear -CLL
Bone Marrow
Hypercellular
Most of the cells are mature lymphocytes
Other cell lines are reduced
AML M0
(no maturation)
AML M1
(minimal maturation)
AML M1- MPO
AML M2 (WITH MATURATION)
AML M3 (promyelocytic)
AML M4 (myelomonocytic)
AML M5 (monoblastic)
AML M6 (erythroleukemia)
AML M7 (megakaryoblastic)
ALL
ALL
Criteria for diagnosis
>30% blasts in the BM
ALL bone marrow biopsy
Massive splenomegaly
Approach to Leukemias
Treatment of leukemias
SUMMARY
Acute Leukemia
accumulation of blasts in the marrow
Significance of adult acute leukemia
a hematologic urgency
usually fatal within weeks to months without chemotherapy
with treatment, high mortality due to disease or treatment-related complications (unlike childhood
acute leukemia)
notify Hematologist promptly if acute leukemia is suspected
Marrow failure
neutropenia: infections, sepsis
anemia: fatigue, pallor
thrombocytopenia: bleeding
Leukostasis
accumulation of blasts in microcirculation with impaired perfusion
lungs: hypoxemia, pulmonary infiltrates
CNS: stroke
only seen with WBC > 50 x 109/L
Constitutional symptoms
fever and sweats common
weight loss less common
Treatment of acute leukemias
Rx is influenced by:
type (AML vs ALL)
age
curative vs palliative intent
Principles of treatment
combination chemotherapy
first goal is complete remission
further Rx to prevent relapse
supportive medical care
transfusions, antibiotics, nutrition
psychosocial support
patient and family
Chemotherapy for acute leukemias
Phases of ALL treatment
induction
intensification
CNS prophylaxis
maintenance
AML treatment
induction
consolidation
Hematopoietic stem cell transplantation
permits rescue from otherwise excessively toxic treatment
additional advantage of graft-vs-leukemia effect in allogeneic transplants
trade-off for allogeneic transplantation: greater anti-leukemic effect but more toxic
Prognosis
If you only remember 4 things from today, remember this:
acute leukemia = too many blasts in the marrow
2 broad categories: AML vs ALL
a hematologic urgency
prognosis is poor in adults; but good in kids with ALL.