Leukemia

LEUKEMIA
IAP UG Teaching slides 2015‐ 1

16
INTRODUCTION
 Leukemias are the most common cancers

affecting children.
 Acute lymphoblastic leukemia (ALL) accounts

for 73%, acute myeloid leukemia (AML)
accounts for approximately 18%.
 Chronic myeloid leukemia(CML) is rarely

seen, accounting for less than 4%.

16
EPIDEMIOLOGY
 ALL: 3–4 cases per 100,000 white children
 Peak incidence between 2 and 5 years of age
 Accounts for 25–30% of all childhood cancers
 In ALL, boys are more commonly affected than girls
 The incidence of AML is similar for all paediatric age

groups

16
INCREASED RISK WITH
 Ionizing radiation
 Chemicals (e.g., benzene in AML)

 Drugs (e.g., use of alkylating agents either alone or in
combination with radiation therapy increases the risk of
AML)
 Trisomy 21 (Down syndrome)
 Bloom syndrome
 Fanconi anaemia

16
 Acute leukemia is characterized by
clonal expansion of immature
hematopoietic or lymphoid precursors.
 Chronic leukemia refers to conditions

characterized by the expansion of
mature marrow elements

16
CLINICAL MANIFESTATIONS
General Systemic Effects

1. Fever (60%).
2. Lassitude (50%).
3. Pallor (40%).
Hematologic Effects Arising from Bone Marrow

Invasion
1. Anaemia – causing pallor, fatigability, tachycardia,
dyspnoea and sometimes congestive heart
failure.
2. Neutropenia – causing fever, ulceration of
buccal mucosa and infection.
16
CLINICAL FEATURES
3. Thrombocytopenia – causing petechial, purpura, easy

bruisability, bleeding from mucous membrane and
sometimes internal bleeding (e.g., intracranial
haemorrhage).
Clinical Manifestations Arising from Lymphoid

System Infiltration
1. Lymphadenopathy
2. Splenomegaly.
3. Hepatomegaly. IAP UG Teaching slides 2015‐ 7

16
CLINICAL FEATURES
Clinical Manifestations of Extramedullary Invasion

 CNS‐ ICT symptoms, seizures
 Genitourinary‐painless testicular swelling
 Bone joints‐ bone pain
 Skin‐bleeds
 Git‐ bleeds

16
INVESTIGATION AND TREATMENT
 Blood count
 Haemoglobin: Moderate to marked reduction
 White blood cell count: Low, normal, or increased
 Thrombocytopenia: 92% of patients have

platelet counts below normal
 Blood smear: Blasts are present on blood smear.
Very few to none (in patients with leukopenia).

16
BONE MARROW
 Leukemia must be suspected when the bone

marrow
contains more than 5% blasts.
 The hallmark of the diagnosis of acute leukemia is
the blast cell, are relatively undifferentiated cell
with diffusely distributed nuclear chromatin, one or
more nucleoli and basophilic cytoplasm.

16
INVESTIGATIONS
 Chest radiograph: Mediastinal mass in T‐cell

leukemia.
 Blood chemistry: Electrolytes, blood urea, uric
acid, liver function tests, Immuno globulin levels.
 Cerebrospinal fluid: Chemistry and cells.
Cerebrospinal fluid findings for the diagnosis of CNS
leukemia require: Presence of more than 5

WBCs/mm3 16
TREATMENT
 In general, treatment regimens for children with newly
diagnosed ALL include three phases: remission
induction, consolidation (or intensification), and
continuation (or maintenance).
 Protocol adopted depends on the institution
 Modified BFM or COG protocol is often the choice

16
INDUCTION
 Prednisolone 60 mg/m2/day
 Inj.VCR 1.5mg2/day
 Inj DNR 30 mg/m2
 L ASPARGINASE 10000u/m2
 MTX I/T

16
INTENSIFICATION & CNS PROPHYLAXIS
 Inj CYCLOPHOSPHAMIDE
1gm/m2
 Inj CYTARABINE 75mg/m2/day
 6 MP 60 mg/m2/d
 I/T MTX
 CRANIAL IRRADIATION
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MAINTENANCE
 Inj. VCR 1.5 mg/m2 one in a month
 Tab PREDNISOLONE 60 mg/m2 for one wk
 T.6MP 50 mg/m2 p.o daily
 T.MTX 20 mg/m2 p.o wkly
The optimal duration of therapy remains unknown. Most investigators

continue to treat patients for 2 to 3 years, based on results of older
studies

16
SUPPORTIVE CARE
 A total of 10 mg/kg/day of allopurinol in divided doses

is
given in all cases before the commencement
of antileukemic drugs.

16
SUPPORTIVE TREATMENT
 Supportive care including the use of packed red cells
 When high fever and possible septicemia occur in

the presence of neutropenia, antibiotic therapy
should be started after taking appropriate blood
cultures and a chest radiograph.(NEUTROPENIA
REGIME)
 Platelet transfusions should be administered to

patients with overt bleeding or when the platelet
count is below 10,000/mm3.
16
RISK STRATIFICATION
Factor Favourable Intermediate Unfavourable
Age (years) 1–9 >/=10 <1 and MLL1
White blood <50 >50
cell count 10
9/L
Immunophenotype Precursor B cell T cell
Genetics Hyperdiploidy .5 Diploid,t(1;19) t(9;22)/BCR‐

0 chromosomes /TCF3‐PBX ABL1,
orDNA t(4:11)/MLL‐AF4,
inde Hypodiploid ,4
x .1.16 ,Trisomies 4
4,10 and 17 , chromosomes
t(12;21)/ETV
6‐ CBFA2
CNS status CNS1 CNS2 CNS3
IAP UG Teaching slides 2015‐
MRD (end <0.01% 16 0.01% to 2>9or=1%
of 0 99%
AML
 Number of risk factors have been identified, including
ionizing radiation, chemotherapeutic agents (e.g.,
alkylating agents,), organic solvents, paroxysmal
nocturnal hemoglobinuria
 Down syndrome, Fanconi anaemia, Bloom
syndrome, Kostmann syndrome, Diamond‐Blackfan
syndrome, Li‐Fraumeni syndrome, and
neurofibromatosis type 1.

16
CLASSIFICATION
 M0 ‐ Acute myeloblastic leukemia

without differentiation
 M1 ‐ Acute myeloblastic leukemia
without maturation
 M2 ‐ Acute myeloblastic leukemia with
maturation
 M3 ‐ Acute promyeloblastic leukemia
 M4 ‐ Acute myelomonocytic leukemia
 M5 ‐ Acute monocytic leukemia
 M6 ‐ Erythroleukemia
 M7 ‐ Acute megakaryocytic leukemia

16
CLINICAL FEATURES
 Anaemia, thrombocytopenia ,leucopenia

 Subcutaneous nodules or “blueberry muffin” lesions (especially in
infants), infiltration of the gingiva (especially in M4 and M5
subtypes)
 Signs and laboratory findings of disseminated intravascular
coagulation (especially indicative of acute promyelocytic
leukemia
 Discrete masses, known as chloromas or granulocytic sarcomas,
typically are associated with the M2 subcategory of AML with a
t(8;21) translocation.

16
DIAGNOSIS & TREATMENT
 Bone marrow aspiration and biopsy specimens of

patients with AML typically reveals the features of
a hypercellular marrow consisting of a
monotonous pattern of cells with features that
permit FAB subclassification of disease.
 Flow cytometry and special stains assist in

identifying myeloperoxidase‐containing cells

16
TREATMENT
 AML‐protocol (Modified from MRC 12)
 Daunorubicin 50 mg/m2 IV days 1, 3, 5
 Cytosine arabinoside 100 mg/m2 IV bolus every

12 hours days 1 to 10 (20 doses)
 Etoposide 100 mg/m2 IV 1 hour infusion days 1

to 5
 Intrathecal cytarabine

16
TREATMENT
 Acute promyelocytic leukemia (FAB‐M3), characterized by a

gene rearrangement involving the retinoic acid receptor
[t(15;17); PML‐RARA], is very responsive to all‐trans‐retinoic
acid (tretinoin) combined with anthracyclines and
cytarabine.

16
Thank You

16

Leukemia

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LEUKEMIA

IAP UG Teaching slides 2015‐ 1

 Leukemias are the most common cancers

 Acute lymphoblastic leukemia (ALL) accounts

 Chronic myeloid leukemia(CML) is rarely

IAP UG Teaching slides 2015‐ 2

 ALL: 3–4 cases per 100,000 white children

 Peak incidence between 2 and 5 years of age

 Accounts for 25–30% of all childhood cancers

 In ALL, boys are more commonly affected than girls

 The incidence of AML is similar for all paediatric age

IAP UG Teaching slides 2015‐ 3

 Chemicals (e.g., benzene in AML)

 Trisomy 21 (Down syndrome)

IAP UG Teaching slides 2015‐ 4

 Chronic leukemia refers to conditions

IAP UG Teaching slides 2015‐ 5

General Systemic Effects

Hematologic Effects Arising from Bone Marrow

3. Thrombocytopenia – causing petechial, purpura, easy

Clinical Manifestations Arising from Lymphoid

3. Hepatomegaly. IAP UG Teaching slides 2015‐ 7

Clinical Manifestations of Extramedullary Invasion

 Bone joints‐ bone pain

IAP UG Teaching slides 2015‐ 8

 Haemoglobin: Moderate to marked reduction

 White blood cell count: Low, normal, or increased

 Thrombocytopenia: 92% of patients have

IAP UG Teaching slides 2015‐ 9

 Leukemia must be suspected when the bone

contains more than 5% blasts.

 The hallmark of the diagnosis of acute leukemia is

the blast cell, are relatively undifferentiated cell

with diffusely distributed nuclear chromatin, one or

more nucleoli and basophilic cytoplasm.

 Chest radiograph: Mediastinal mass in T‐cell

 Blood chemistry: Electrolytes, blood urea, uric

acid, liver function tests, Immuno globulin levels.

 Cerebrospinal fluid: Chemistry and cells.

Cerebrospinal fluid findings for the diagnosis of CNS

leukemia require: Presence of more than 5

 In general, treatment regimens for children with newly

diagnosed ALL include three phases: remission

induction, consolidation (or intensification), and

continuation (or maintenance).

 Protocol adopted depends on the institution

 Modified BFM or COG protocol is often the choice

IAP UG Teaching slides 2015‐ 12

 Inj DNR 30 mg/m2

IAP UG Teaching slides 2015‐ 13

 Inj CYTARABINE 75mg/m2/day

 Inj. VCR 1.5 mg/m2 one in a month

 Tab PREDNISOLONE 60 mg/m2 for one wk

 T.6MP 50 mg/m2 p.o daily

 T.MTX 20 mg/m2 p.o wkly

The optimal duration of therapy remains unknown. Most investigators

IAP UG Teaching slides 2015‐ 15

 A total of 10 mg/kg/day of allopurinol in divided doses

given in all cases before the commencement

IAP UG Teaching slides 2015‐ 16