ACUTE LEUKEMIAS

ACUTE LEUKEMIAS

• They are clonal malignant neoplasms of the

haemotopoietic stem cells characterised by
uncontrolled proliferation of abnormal (Leukemic) blast
cells and impaired production of normal blood cells.
 Acute Chronic

Age All ages Usually Adults

Clinical course Sudden Aggressive Insidious less aggressive

Course if untreated 6 month 2-6 years

Anemia &
Prominent Mild
Thrombocytopenia

WBC Variable Increased

Lymphadenopathy
Mild Prominent
Splenomegaly
ACUTE MYELOID LEUKEMIA

• Median age is 60 yrs.

• M>F.
ETIOLOGY

1. Hereditary.
– Down’s, patau, klinefelter syndrome.
– Fanconi anemia, bloom syndrome.
– Ataxia telengiectasia.
– Kostmann sydrome ( congenital neutropenia).
2. Radiation
– High dose.
– Shorter time.
– Younger age.
3. Chemicals
– Benzene.
– Ethylene oxide.
– Herbicides & pesticides.
– Smoking.
– Drugs – Alkylating agents.
- Topoisomerase II inhibitor.
CLASSIFICATION

1. FAB classification.
WHO CLASSIFICATION
CLINICAL FEATURES

1. Decreased marrow function.

Anemia- Fatigue, headache, pallor, angina, ccf.
Thrombocytopenia – Petechiae, ecchymoses.
Gum bleeding, epistaxis.
Granulocytopenia.
2. Infiltration of organs
Lymphadenopathy.
Hepatomegaly.
Splenomegaly.
Bone – Pain, sternal tenderness.
skin - Leukemia cutis – Raised non pruritic rash.
Soft tissues – chloroma or granulocytic sarcoma(M2).
Gingival infiltration(M5).
NON SPECIFIC

• Fever.
• Headache.
• Anorexia.
• Weight loss.
• M3 –DIC.
• M4 & M5 – Extramedullary involvement.
• M6 – long prodromal phase.
DIAGNOSIS

• Anemia.
• Thrombocytopenia.
• WBC – Variable.

• Morphology – 12-20 nm.

- Discrete nuclear chromatin.
- Multiple nucleoli.
- Abundant cytoplasm with azurophilic

granules
Auer rods-virtually pathognomonic
Bone marrow-> 20% blasts establish diagnosis
DIAGNOSIS (Contd..)

Others - Uric acid

LDH
PT, PTT
Fibrinogen
Myeloblasts with auer rods
Lymphoblast
TREATMENT

Goal – 1. Induce a complete remission

Blood – Neutrophil count > 1000/μl
- Platelet count > 1,00,000 μl
- No circulating blasts
Bone marrow – cellularity > 20% with trillineage
Maturation
- <5% blasts
- No Auer rods
- No extramedullary leukemia
2. Restoration of normal marrow function
PREPARATION

- Treat Anemia, Bleeding Infection

- - Prevention of tumour lysis syndrome
- Major organ dysfunction
TREATMENT

- Remission induction
cytarabine + Anthracycline ± Etoposide
[7 and 3 regimen]

-Post remission therapy

- High dose cytarabine
- Cytarabine + Daunorubicin
- Recurrent disease
- Retreatment as before
- Gemtuzumab ozogamician in elderly

- Stem cell transplantation

- Adv – improved disease free survival
- Disadv- High treatment related mortality
PROGNOSIS

Favourable Unfavourable
T(15:17) T(6:9)
Cytogenetics T(8:21) Inv (3)
Inv 16 De1 5 or 7

Age < 60 years >60 years

WBC < 10,000 >1,00,000

DIC - +

Auer rod + _

Bone marrow
response to <5% >20%
remission induction
Promyelocytic leukemia
- Tretinoin
- Not effective in other forms
- Leads to retinoic acid syndrome

Arsenic trioxide
 AML – M1
• Note the myeloblasts and the auer rod:
 AML – M2
• Note myeloblasts and hypogranulated PMNs:
 AML – M3
• Note hypergranular promyelocytes:
 AML – M3m
• Note hypogranular promyelocytes:
 AML – M4
• Note monoblasts and promonocytes:
 AML – M5A
• Note monoblasts:
 AML-M5B
• Note monoblasts, promonocytes, and
monocytes:
 AML – M6
• Note M1 type monoblasts
Acute lymphoblastic leukemia

- 75% of child hood leukemias

- Peak incidence – 3-7 years
- -M>f

Aetiology
-Hereditary As for AML
Radiation
Viruses- EBV
HTLV
CLASSIFICATION
CLINICAL FEATURES

- Similar to AML
- Extramedullary sites are frequently involved
- CNS involvement – Headache
- vomiting
- nuchal rigidity
- papillaedema
- Testicular involvement – unilateral
- painless
- Mediastinal mass
DIAGNOSIS

Blood – similar as AML

- Lymphoblasts >20% in bone marrow
CSF – Even a single blast indicates involvements
TREATMENT

Induction – Vincristine 1.5mg/m2/week

3-4 wks prednisolone 40mg/m2/day
L-Asparaginase 10000/m2 thrice weekly
Daunorubicin 20mg/m2/week

CR -90% children
80-90 Adults
Consolidation-
Methotrexate (MTx) iv
Cytarabine iv
Daunorubicin iv
Etoposide iv
Cyclophosphomide
Maintenance –
6 Mp (oral)
MTx (oral)
Prednisolone (oral)
Vincristine (oral)
CNS prophylaxis-
- Intrathecal methorexate
- Triple therapy – MTx
- hydrocortisone
cytarabine
- Cranial radiation- 2400 CGY

Relapse–
Retreatment with induction regimen
stem cell transplantation
PROGNOSIS

Poor – Male
Age < 1 yr or > 9 years
Mediastinal mass
CNS involvement
Time to remission > 4 weeks
WBC > 50,000/cmm
t(9:22) t(1:19) t(4:11)
SUPPORTINE

Anemia– Maintain Hb> 10g

Bleeding -Platelets FFP
Infection – Bacterial
fungal
Herpes
Tumorlysis Syndrome
ALL-L1
ALL-L2
ALL-L3
Thank you!