ACUTE LEUKEMIA

DEFINITION
• ALL:
• malignancy of the hematopoietic tissue
• generalized from the start
• lethal constant evolution
• characterized by clonal expansion of lymphoid
precursor cells (with blocking of cellular differentiation
and maturation)
• invasion of the bone marrow and of other organs

• INVASION OF THE BONE MARROW IS MANDATORY!

• ALL: lymphoblast percentage in bone marrow analysis is
higher than 25%
• Non-Hodgkin Lymphoma: lymphoblast percentage in
bone marrow analysis is lower than 25%
 STATISTICS

• The most frequent malignancy in children

• 30% of all infant cancer cases
• Peak incidence 2-5 years (for ALL)
• Incidence in NLAL is constant from birth to 10 years and it
grows in adolescence
 CLASSIFICATION (1)
• Characterization of blast cells by :
• Morphology (peripheral blood smear examination
and bone marrow examination)
• Cytochemistry:
• cytoplasmic biochemical markers
• Non-enzymatic reactions: PAS, Sudan Black
• Enzymatic reactions: peroxidase, alkaline phosphatase
• surface immune-markers
• ALL with B cells: CD19, CD22, CD20, CD21, CD10
(detected in 90% of all ALL with B cells)
 Characteristics LYMPHOBLAST MYELOBLAST

Cell size 10-20μm 14-20μm

Nuclear
shape round/oval/indented rotund/ovalar
Chromatin homogeneous inhomogeneous, spongy
Nucleoli 0-2 or 2-5 distinguished
indistinguished
Nuclear membrane regular iregular
Nuclear-cytoplasmic high low
ratio
Cytoplasm
colour blue Blue-greyish
quantity scanty moderately abundant
Auer rods absent present
 LYMFOBLAST
-OPTICAL MICROSCOPY -
 MYELOBLAST
-OPTICAL MICROSCOPY -
 CLASSIFICATION (2)
• FAB classification of ALL by
morphology:  immunophenotipical
• L1 Classification:
• Most frequent type of ALL in  ALL with B-
children (85%) precursor cells
• Common form in children  ALL with T cells

• L2  ALL with B cells

• Incidence 14%
• Frequently associates cytogenetic
features with unfavorable
outcome
• L3
• Rare (1%)
• L3 lymphoblasts correspond to
mature B cells (similar to Burkitt
lymphoma cells)
FAB Inci- General features Associated
type dence particularities

M0 2% Agranular blasts with minimal myeloid Frequent

differentiation, myeloid reaction, expression of
negative Sudan black, expression of at CD34 and of Tdt
least one myeloid antigen (CD13 and/or enzyme
CD33)
M1 10-18% -rarely differentiated myeloblasts
- Visible Auer rods (ocazionally)
M2 27-29% - Differentiated myeloblasts (<20% Myeloblastoma
monoblasts) (most frequent
-corpi Auer proeminenţi orbital)
M3 5-8% -hypergranular promyelocites intravascular
- Auer rods disseminated
coagulation (IDC)
M3V 2% M3 version, promyolocites with rare or
absent granulations, few Auer rods
FAB Inci- General features Associated
type dence particularities

M4 16-25% Myeloblasts and monoblasts Infant Leukemia

(monoblasts are predominant: 20- (frequently
80%) extramedullary)
M4E0 M4 version with over 5%
abnormal eosinophilic cells into
the bone marrow
M5 13-22% M5a: subtype with monoblasts Extramedullary
being predominant (> 80% of all leukemia in infants
leukemic cells) Secundary leukemia
M5b: subtype with < 80% after
monoblasts of all leukemic cells epipodophyllotoxines
M6 1-3% Erythroleukemia
M7 4-8% Megakarioblasts and medullary Down Syndrome
fibrosis
CLINICAL AND PARACLINICAL CORRELATIONS
(1)

 Peripheral pancytopenia ( through

medullary blastic infiltration)
 Anemia
 Thrombocytopenia
 Neutropenia
CLINICAL AND PARACLINICAL CORRELATIONS (2)

• Anemia (Hb: 2.4 - 14g/dl)

• Clinical features: pallor, anorexia, tachycardia, systolic murmur

• Thrombocytopenia (PLT < 50.000/mmc in over

50% cases)
• Thrombocytopenia <10.000/mmc can show ICD (relatively frequent in
acute promyeloblastic leukemia - M3)

• Clinical features:
• Cutaneous hemorrhagic syndrome (petechiae, bruising, purpura)
• Epistaxis
CLINICAL AND PARACLINICAL CORRELATIONS (3)

• Neutropenia
• Increases the risk of infections
• Erythemato-pultaceous angina,
pneumonia, stomatitis
• WBC variates from leukopenia to
hyperleukocytosis
• Hyperleukocytic leukemia has the risk of
leukostasis
• In NLAL the risk of leukostasis is even
higher than in ALL.
CLINICAL AND PARACLINICAL CORRELATIONS (4)

EXTRAMEDULLARY INFILTRATIVE SYNDROME

• Hepatosplenomegaly and superficial adenopathies
• more frequent at the beginning of the disease
• Mediastinal adenopathies and infiltration of the thymus
• in T cells ALL
• When the volume of the mediastinal masses is too high, superior
vena cava syndrome may develope (through SVC
compression), showing:
• Acute respiratory failure, jugular turgescence, upper body
edema (Stokes collar)
• Facial cianosis, cough
• Osteoarticular symptoms (more frequent in ALL)
• Pain in bones and joints
CLINICAL AND PARACLINICAL CORRELATIONS (5)

• CNS Leukemia (leukemic meningitis)

• Incidence of 5% in ALL
• Incidence of 15% in NLAL
• Mandatory criteria of positive diagnosis: at
least 5 blastic cells/μl in the cerebrospinal
fluid
• Polimorphic neurological symptoms with
diffuse or focal features
• Intracranial hypertension symptoms
(headaches, vomiting, papilloedema,
cranial nerves VI and VII paresis, neck
stiffness)
• Gastrointestinal symptoms
 CLINICAL AND PARACLINICAL CORRELATIONS
(6)

• Testicular leukemia
• Local soreness and swelling
• Eye symptoms
• Retinal hemorrhage and papilledema

• Cutaneous blastic infiltration (leukemic infiltration)

• in 50% of all congenital leukemias
 TREATMENT
• OBJECTIVES:
• Eradication of blast cells (through chemotherapy or
radiotherapy)
• Prevention and treatment of infectious complications
• Supportive haematological treatment

• PROTOCOL of treatment:
• induction phase (of complete remission)
• consolidation and intensification phase
• maintenance phase
 EVOLUTION

• Constantly leads to death in absence of

treatment
• Complete remission (first aim of treatment) is
defined by:
• disappearance of symptoms
• Normalization of CBC and of the bone marrow analysis
(medullar blast cells <5%)
• Persistence of minimal residual bone marrow disease
(objectified by PCR); during complete remission this is
an unfavorable prognostic factor

• Partial remission is defined by:

• Persistence of some clinical signs
• Medullar blast cells: 5% - 25%
 OUTCOME
• FAVORABLE PROGNOSIS FACTORS:
• Ages 1 to 9 years
• female
• WBC initially < 10 000/mmc
• Absence of an important tumoral syndrom
• B morphological type, B immunophenotype, presence
of CALLA antigen
• UNFAVORABLE PROGNOSIS FACTORS:
• Males, ages <1 year and > 9 years
• WBC initially > 50 000/mmc
• Presence of CNS leukemia from the start
• T cellular immunophenotype, the presence of Ph1
cromosome and of 4:11 translocation.