Clinical aspect & therapy of

acute leukemia
 What’s malignancy?
Neoplasma, cancer, malignancy
• Product of an imbalance situation
(oncogenes vs tumor supressor genes)
• Uncontrolled growth,
• Destructive, metastasis
 LEUKEMIA

Leukemia:
marrow malignancy
maturation arrest
uncontrolled proliferation
occupation & suppression
 Bone marrow

Albumin 58%
Protein 7%C Globulin 38%
Fibrinogen 4%
Air 90%
Plasma
Plasma
Darah 55%B
55% Terlarut lain 3% Ion, nutrien, gas,
‘sampah’, dll
8%A
Netrofil 55%
Seluler Trombosit
Limfosit 36%
45% Lekosit Monosit 3-8%
Eritrosit Eosinofil 1-4%
Basofil 0,5-1%
 Leukemia
The marrow occupied by blood malignant cells
Acute: young cells domination
Chronic: young and mature cells

ALL

AML
 Classification

A. Cells origin & natural history

ALL (Acute Lymphoblastic Leukemia, 85%)
AML (Acute Myeloblastic Leukemia/ANLL, 12%)
CML (Chronic Myeloblastic Leukemia, 2%)
CLL (Chronic Lymphoblastic Leukemia)
B. Morphology (FAB), Histochemistry
ALL (L1, L2, L3) it’s not staging!
AML (M0 - M7)
C. Immunophenotyping
ALL or AML
T and B lineage, maturation phase of ALL
 Leukemia & childhood cancer
Leukemia: most common malignancy in childhood < 15 y,
1:25.000 populations?, peak at 2-5 years of age

ALL 94
144
AML 38 (n = 592)
37

Retinoblastoma 17 56.5 % - Leukemia

24
6.9 % - Retinoblastoma
NHL 12 6.7 % - Lymphoma
28
10 Female
Neuroblastoma 17
Male
CML 9
13

Osteosarcoma 10
7
Hepatoblastoma 7
11

Others 46
68

0 50 100 150 200

TotalHospital,1996-2003
Childhood cancer in Dr. Sardjito
 Acute leukemia

ETIOLOGY
Unknown
Suspected causes
• Radiation
• Chemicals (benzene in AML)
• Drugs (alkylating agents + Radiotherapy)
• Genetic
• identical twins,
• siblings,
• chromosomal abnormality (Down syndrome, Fanconi)
• congenital agammaglobulinemia
 Clinical findings of acute leukemia

ANAMNESIS
• Natural history
• acute
• progressive
• Risk factors
• not always clear

PHYSICAL
1. General appearance
• Fever (60%)
• Lassitude (50%)
• Pale (40%)
 Clinical findings of acute leukemia

2. Signs of marrow suppression

• Anemia (pallor, fatique, tacchycardia, dyspneu, cardiac failure)
• Neutropenia (fever, infectios, ulcers)
• Thrombocytopenia (bleeding in skin, mucous, ICH)
 Clinical findings of acute leukemia

3. Sign of invasion to lymphoid organs

• lymphadenopathy
(neck, axilla, inguinal, mediastinum/svcs)
• splenomegaly
• hepatomegaly

4. Ekstramedullary invasion: CNS (<10% at dx)

• ICP (headache, vomitting, papilledema, palsy N VI)
• brain parenchym (hemiparesis, palsi Nn cranialis, seizure)
• hypothalamic syndromes (poliphagi, obese, hirsutism, behaviour changes)
• cerebellum (ataxia, dysmetri, hypotoni, hyperreflexies)
• Intracranial hemorrhages (leukostasis/thrombi, thrombositopenia)
 Clinical findings of acute leukemia

5. Genitourinary tract invasion

•Testicles (tenderless enlargement, bilateral)
• Ovarium, (rarely)
• Priapism (rarely, leukemic cells obstruct corpus cavernosum)
• Kidneys (hematuria, hypertension, renal failure)

6. Gastrointestinal tract invasion

• common
• most common as GIT bleeding
• typhylitis (necrotizing enteropathy of cecum by leukemic cells)
 Clinical findings of acute leukemia

7. Invasi tulang & sendi (25% kasus saat dx)

• Nyeri tulang
(infiltrasi periosteum, infark tulang, lesi osteolitik)

8. Invasi kulit
• paling sering pada leukemia neonatal

9. Invasi jantung
• sering tanpa gejala, ditemukan saat otopsi
• infiltrat dan perdarahan

10. Paru
• Infiltrat, perdarahan
 Diagnosis of acute leukemia

1. Clinical findings
2. Peripheral blood
• Hb, normositic normochromic
• WBC , normal, or 
• Smear: blast
• Thrombocytopenia (92% at dx)
3. Bone marrow aspirates (gold standard)
• Blast > 25% (may reach 80-100% at dx)
• Megakaryocytes & erythroblast 
• Blast morphology
ALL (L1, L2, L3) or AML (M0-M7) FAB criteria
• Cytochemistry (PAS, Sudan Black B)
ALL or AML
• Immunophenotyping
ALL or AML
lineage & maturation stage of ALL
• Cytogenetic (chromosomal abnormality)
 Diagnosis of acute leukemia

4. Chest X ray (mediastinal mass in T cell ALL)

5. Blood chemistry (electrolytes, LFT, RFT)
6. CSF (leukemic cells in CSF)
7. Coagulation profiles (seldom  in AML)
8. Skeletal survey (lesion & bone mass)
9. Cardiac test (ECG, echocardiography)
 Risk grouping in childhood ALL

Stated at time of diagnosis for treatment choices

High risk group
• WBC at diagnosis > 50.000/mmk
• Age < 1 year or > 10 years
• Infiltration to mediastinum, testicle or CNS
• T cell
Standard risk group
• Out of high risk group
 Management of acute leukemia

Aims
1. To achieve remission
2. To sustain remission & prevent infiltration (CNS, testicle)
3. To overcome treatment-related complications

• Remission
Blast in marrow < 5% at the end of induction phase
No blasts found in peripheral blood
No signs of blasts infiltration

• Relapse
signs of blast infiltration found in bone, testicle, CNS
Blast in marrow > 5%
 Management of acute leukemia

Chemotherapy as the main treatment!

Based on risk group
may be changed based on its response
Radiotherapy?
Supportive care
Anti-infection (antibiotic, fungus, virus)
Cancer pain reliever (paracetamol, phenobarbital, codein)
Blood component
Nutrition, hygiene
Psychology
Education
Patient, parent, family
 Management of acute leukemia

Major toxicities of chemotherapies in ALL treatment

Vincristine neuropathy
Corticosteroid obesity, behaviour, hypertension, ulcetr
Asparaginase allergy, pancreatitis
Daunorbicine myelosuppression, cardiotoxic
Metothrexate myelosuppression
6-Mercaptopurine myelosuppression
Cyclophosphamide myelosuppression
Cytosine Arabinose myelosuppression
 Management of acute leukemia

Prognostic factors at diagnosis of ALL

• Age, sex, cytogenetics, signs of infiltration
• Initial level of Hb, platelet, WBC, % blast
• FAB classification
• Immunophenotyping
• Drug resistance-related protein expression
• Nutritional status
 Problems in acute leukemia

1. Attention, awareness: low?

2. Diagnosis (experience, facilities)
3. Treatment related
Response, drug resistant
Side effects: marrow suppression (infection, bleeding)
Facilities & human resources
Access to chemotherapy,
Supportive care
4. Emergency situation
Tumor lysis syndrome
Febrile neutropenia/severe infections
hemorrhage, DIC
5. Psycho-social-economy burdens
Compliance of treatment
high cost, catastrophic
 Problems in acute leukemia

6. Prognosis
Progressive, fatal during months
Generally AML is worsened than ALL
From death to 80-90% cured with adequate treatment
depend on cells characteristics, regime & response to
treatment
Role of researches
 Role of doctors in leukemia

Early detection, follow up, treatments?