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 Age Clinical course Course if untreated Anemia & Thrombocytopenia WBC All ages Sudden Aggressive 6 month Prominent Variable Mild

Chronic Usually Adults Insidious less aggressive 2-6 years Mild Increased Prominent

Lymphadenopathy Splenomegaly

ACUTE MYELOID LEUKEMIA

Median age is 60 yrs. M>F.

ETIOLOGY
1.

2.

Hereditary.

3.

Radiation

Downs, patau, klinefelter syndrome. Fanconi anemia, bloom syndrome. Ataxia telengiectasia. Kostmann sydrome ( congenital neutropenia). High dose. Shorter time. Younger age. Benzene. Ethylene oxide. Herbicides & pesticides. Smoking. Drugs Alkylating agents. - Topoisomerase II inhibitor.

Chemicals

CLASSIFICATION
1.

FAB classification.

WHO CLASSIFICATION

CLINICAL FEATURES
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).
1.

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 granules Auer rods-virtually

azurophilic

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/l - Platelet count > 1,00,000 l - 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 Cytogenetics

Unfavourable

T(15:17) T(8:21) Inv 16

< 60 years

T(6:9) Inv (3) De1 5 or 7

>60 years

Age

WBC DIC
Auer rod Bone marrow response to remission induction

< 10,000 +

>1,00,000 +
_

<5%

>20%

Promyelocytic leukemia - Tretinoin - Not effective in other forms - Leads to retinoic acid syndrome
Arsenic trioxide

AML M1

Note the myeloblasts and the auer rod:

Acute lymphoblastic leukemia

- 75% of child hood leukemias - Peak incidence 3-7 years - -M>f Aetiology -Hereditary As Radiation for AML 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 3-4 wks weekly Daunorubicin 20mg/m2/week CR -90% children 80-90 Adults Vincristine 1.5mg/m2/week prednisolone 40mg/m2/day L-Asparaginase 10000/m2 thrice

ConsolidationMethotrexate (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!