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ACUTE LEUKEMIAS
Acute meyeloblastic and acute lymphoblastic
leukemia
 Acute leukemia
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AML (acute myeloid leukemia) and ALL (acute

lymphoblastic leukemia)
Definition:
Clonal neoplastic disorder characterized by
proliferation and accumulation of immature and
malignantly transformed cells in the BM or blood;
resulting in abnormal or insufficient haemopoiesis.
 AL manifests with normal blood cell cytopenias
with/with out abnormal cell leukocytosis in peripheral
blood, and various organ infiltrations
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AML
 Incidence increase with age
 Median age at presentation is 60-65 yrs (M>F)
 Constitutes 80% of adult AL, 46% of all leukemia

ALL
 Peak incidence at 3-4 yrs, decrease after 9 yrs (rare
>40 yrs); M>F
 Constitutes 20% of adult AL, 11% of all leukemia
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Aetiology of AML : most cases unknown

 Association factors
 Pre-existing myelodysplasia
 Previous cytotoxic chemotherapy(Alkylating agents/
Topoisomerase II inhibitors)
. Ionizing radiation
. Hereditary: Chromosomal abnormalities
Down’s syndrome / Fanconi anemia/ ataxia
telangiectasia
. Chemicals: Benzene exposure
. Smoking
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 Aetiology of ALL- Unknown

 Predisposing factors
 Ionizing radiation
 Chromosomal abnormalities- Down’s syndrome/Fanconi
anemia
 Agricultural chemicals

 Industrial exposures

 Smoking
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Classification of AL depends on
 Clinical features

 Morphological appearance in BM and peripheral blood

smear
 Cytochemical studies

 Sudan black stain

 Myeloperoxidase stain
 Esterase stain (chloroacetate and non-specific esterase stain)

 Electron microscopic appearance

 Immunophenotypic studies
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 Cytogenetic studies/ Microarray analysis for gene

expression profiles

 FAB classification of AL: based on morphologic and

cytochemical studies

 WHO classification
 Clinical feature included
 Cytogenetic studies and molecular studies
 morphology included
 Comprehensive but not applicable in all setting
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AML (incidence in adults)

 M0: AML, with minimal differentation- blasts >90% (<5%)
 M1: AML, without maturation - blasts >90% (15%)
 M 2: AML, with maturation- >50% myeloblasts and
promyelocytes (25%)- commonest type of AML
 M3: Acute promyelocytic leukemia (Hypergranular and
microgranular types) (10%)
 M4: Acute myelomonocytic leukemia (25%)
 M5: Acute monoblastic leukemia (10%)
 M6: Acute erythroleukemia (<5%)
 M7: Acute megakaryoblastic leukemia (<5%)
 Morphologic classification of ALL
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ALL(incidence)
 L1: ALL, child form (30%)
 Small monomorphic type- small homogenous blasts, single
inconspicuous nucleolus, regular nuclear outline
 L2: ALL, adult form (65%)
 Large heterogeneous type-larger blasts, more pleomorphic
multinucleate, irregular frequently clefted nuclei with
conspicuous nucleoli
 L3: ALL, burkitt type (5%)
 Burkitt-cell type- Medium sized homogenous blasts, with
round nuclei, multiple nucleoli, and basophilic cytoplasm with
cytoplasmic vacuoles
 Immunological classification of ALL
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B-lineage ALL (75% in adults)

. Precursor B-cell ALL (early pre-B or pre-pre-B cell
ALL) (10% of adult ALL)
. Common ALL: >50% of adult ALL
. Pre-B ALL: 10% of adult ALL
. Mature B-cell ALL or Burkitt-cell ALL: 4% of adult ALL
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T-lineage ALL (25% in adults)

. Early-T ALL: 7% of adult ALL
. Thymic ALL: The most common T-cell ALL
. Mature T-ALL: 17% of adult ALL
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Clinical features:
Symptoms
. Usually acute presentation due to bone marrow failure
. Fatigue, weakness, palpitation and dyspnea
. Mucocutaneous bleeding (M3-DIC/ALL)
. High grade fever due to infection (chest, mouth, perianal,
skin)
. Low grade fever, loss of appetite and weight and sweating
due to hypermetabolic state
. Headache, nausea, vomiting, blurred vision, CN palsy,
seizures due to CNS involvement
. Abdominal fullness, early satiety
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Signs
. Fever
. Signs of organ infiltration
. Gingival hypertrophy and skin infiltration
(M4/M5/ALL)
. LAP and organomegaly (ALL*/AML)
. Bone tenderness
. Soft tissue tumors (chloroma/granulocytic sarcoma)
and cutaneous nodules (leukemia cutis)
. Meningitis and CN palsy (ALL//M5 )
. Signs of leukostasis- hypoxia, diffuse pulmonary
shadowing, retinal haemorrhage, confusion
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Investigations
. CBC, ESR, Blood typing and cross-matching
. Peripheral morphology
. CXR/CT of chest, abdomen, brain
. Biochemistry panels: LFT, RFT, electrolytes including
calcium and phosphate, uric acid, LDH
. Coagulation profiles:PT, aPTT, FDP, fibrinogen, D-dimer
. LP (with indications)
. HLA-typing for allogeneic-SCT eligible pts
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Characteristic lab. Features in AL

. NCNC anemia in 90% of pts at presentation,
normoblasts may be seen in peripheral smear
. Thrombocytopenia in 90% of pts (<50,000/µl in 50%
of pts)
. Leukocytosis in 60% of cases, normal WBC count in
15% and leukopenia (<5,000/µl) in 25%
Circulating blasts seen in most cases of AL except in
Aleukemic leukemia (few or no blasts in peripheral
blood but BM is packed with blasts)
. AL is defined as percentage of blasts ≥20% in
peripheral blood or BM
 Uniform population of primitive myeloblasts with immature
chromatin, nucleoli in some cells, and primary cytoplasmic
granules
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 Leukemic myeloblast containing an Auer rod
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 Promyelocytic leukemia cells (M3) with prominent
cytoplasmic primary granules
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 Acute lymphoblastic leukemia: The cells are heterogeneous in size, have
round or convoluted nuclei, high nuclear/cytoplasmic ratio, and absence of
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cytoplasmic granules (L2 type of ALL)
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DDX
 MDS/MPD

 High-grade lymphoma

 Aplastic anemia

 Metastatic carcinomatosis (breast/lung ca)

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Rx
Emergency treatment
. Cardiovascualr and respiratory resuscitation if pt in
septic shock or with massive bleeding
. Empirical broad spectrum antibiotics for neutropenic
sepsis
. Hydration and alkalinization of urine to prevent acute
tumor lysis syndrome (TLS) in pts with WBC count >
100, 000/µl
. Leukopharesis if WBC count > 100, 000/µl or signs of
leukostasis present
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 Supportive care
 Blood component therapy: Packed red cell
transfusion/platelet concentrate transfusion
 Broad spectrum antibiotics for fever after collection
of specimen for culture from blood /urine /skin
/sputum
 Reverse-isolation
 Prevent or treat leukocytosis-induced hyperviscosity
syndrome (leukostasis) with leukapheresis, cranial-
irradiation or hydoxyurea
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Specific therapy
. Chemotherapy or haematopoietc stem cell transplantation
(HSCT)
Chemotherapy
Goal of chemotherapy: Eradicate leukemic clone and re-
establish with normal haemopoiesis in the BM
Long-term survival is seen in those pts who achieve complete
remission (CR)
Treated cases may die from infection during therapy
Median survival in untreated cases or unresponsive pts is 2-
3 months, mainly die from marrow failure complications
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Phases of chemotherapy
1. Remission induction chemotherapy: Eliminate
leukemic cells and achieve CR
2. Post-remission chemotherapy: Chemotherapy
given after achieving CR to eradicate residual
leukemic cells to prevent relapse
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Components of Post-remission chemotherapy

 Consolidation chemotherapy: Repeated courses of
same drugs used in induction therapy after
achieving CR
 Intensification chemotherapy: Higher doses given

than used in induction therapy

 Maintenance chemotherapy: Small doses are given

according to certain schedule for long period

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Definition of CR
. Normal BM (normal cellularity with <5% blasts)
. No blasts in the peripheral blood
. Normalized leukocytes (>1500/µl), platelets
(>100,000/µl), and red cells
. No sign of extramedullary leukemia
. Normal performance status
2. HSCT
. Curative therapy and effective modality of treatment
Source: another person, usually related or matched
unrelated donor (allogeneic-SCT), identical twins (syngeneic-
SCT) or self (autologous-SCT)
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Rx of AML
 7+3 regimen: Cytarabine for 7 days +
Idarubicin/daunorubicin for 3 days
 CR is achieved in 60-80% of pts with good supportive
care
 Consolidation-intensification regimen with
cytarabine for 2-4(6) cycles after CR
 Allogeneic-SCT in pts <50yrs, especially in pts with
poor prognostic features
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 CNS prophylaxis or Rx: Intrathecal (IT) cytarabine

or methothrexate or/and cranial irradiation
 Median survival after CR is 1-2 yrs; median
duration of 1st CR is 1yr
 20-40 % of pts who achieve CR survive ≥ 5yrs
(considered cured)
 Most relapses occur with in 3yrs
 Poor prognostic feature of AML
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 Advanced age (>50yrs)

 Poor performance status
 High WBC count at diagnosis (>100,000/µl)
 Secondary AML (after MDS or chemotherapy –
related)
 Unfavourable karyotype
 FAB subtype: Mo/M5/M6/M7
 Failure to achieve CR with 1st cycle of induction
therapy
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Rx of ALL
 Remission induction chemotherapy

. Vincristine and prednisolone based regimen

Vincristine + prednisolone + daunorubicin ±
L-asparaginase ± methotrexate (IT)
 CNS prophylaxis or therapy: IT methotrexate

CNS leukemia at diagnosis occur in 6% of pts; pts

not receiving CNS prophylaxis have CNS relapse
rate of 30%
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65-85% of pts achieve CR; leukaemia–free survival of

30-40% at 5 yrs; duration of 1st CR is 1-2 yrs
 Post-remission therapy: consists of intensive rotational
consolidation therapy, intensification chemotherapy and
HSCT
 Maintenance therapy is given for 3yrs with
methotrexate and 6-mercaptopurine
NB: cure rate in children is 90% where as long term
disease free survival is 50% in adults ( more
unfavourable cytogenetic abnormalities in adult ALL)
 Poor prognostic features in ALL
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. Age <2yrs and >10 yrs, adults >35 yrs

. WBC count at diagnosis (>30,000/µl in precursor- B ALL/
>100,000/µl in precursor T-ALL)
. Immunophenotype- Pro-B ALL and Pro-T ALL - poorer
outcome
. Presence of unfavourable cytogenetic abnormalities:
Ph1chromosome in ALL
. Time to achieve CR >1month
. Presence of symptomatic CNS disease
. High level of residual disease at induction and
consolidation therapy
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 Thank you