HEMATOLOGY CLINICAL MANIFESTATIONS OF ANEMIA (thrombocytopenia - may suggest bone marrow failure)

HISTORY
ANEMIA ❏ Age: iron deficiency is never seen >6 mos (unless preterms)
MECHANISM OF ANEMIA (how it develops)
DEFINITION Because of maternal iron factors during fetal dvt
1. RBC are not made (production disorder - hypoproliferative anemia)
❏ Reduction in red cell mass or blood hemoglobin ❏ Gender: common in girls,
2. RBC are lost (bleeding - occult blood or gross blood)
G6PD deficiency is X-linked - manifested in boys
concentration 3. RBCs are destroyed (hemolytic anemia)
❏ Race:
❏ Normal limit is at 2 standard deviations below the Hb S and C - Americans
Ask for RETICULOCYTE COUNT to differentiate
NOTE: more than 1 physiologic mechanismcan happen (usually one predominates)
mean for an age- and gender-matched population Alpha-thalassemia - Asians & Americans RETICULOCYTE COUNT (Normal value: 1-5%)
❏ It is not its own disease, but an expression of Beta-thalassemia - whites  Direct reflection of rate of RBC production
underlying disorder newborn screening: Hemoglubinopathies  Indirect reflection of rate or RBC destruction
❏ NOT A DIAGNOSIS BUT A COMPLICATION (2ndary to) ❏ Ethnicity: Thalassemias are common in mediterranean origin INCREASED in disorders with unstable hemoglobins,
FACTORS AFFECTING HGB LEVELS ❏ Neonatal course: pathologic jaundice (>weeks), prematurity membrane defects, enzyme deficiencies
❏ Age ❏ Diet: B12 and folate consumption; & pica . (Thalassemia, Spherocytosis, G6PD deficiency)
❏ Race ❏ Drugs: G6PD (hemolysis) , cotrimoxazole (oxidative stress to RBC) DECREASED in disorders of heme synthesis
 Americans - 0.5 g/dL is lower than in whites ❏ Infections: Post-hepatitis aplastic anemia, red cell aplasia . (iron deficiency, lead poisoning, inflammation)
 Hispanics has more Hgb level than whites ❏ Family History: Gallstones & Splenomegaly/splenectomy
may suggest increase risk of hemolytic CLASSIFICATIONS
❏ Gender
anemia
❏ Sexual maturity Mechanistic
PHYSICAL EXAMINATION A. HYPERPROLIFERATIVE ANEMIAS
❏ Parent’s hemoglobin
❏ Glossitis - atrophic tongue (seen in iron & B12 deficiency)  Generally hemolytic
❏ Geographic location ❏ Angular cheilitis - corner of lips  Associated with jaundice, dark urine, splenomegaly
 Himalayas - increase Hgb due to low oxygen & bone ❏ Koilonychia - spooning of nails (chronic anemia) Extramedullary erythropoeisis compensates leads to splenomegaly
marrows produces more RBC & Hgb ❏ Splenomegaly, jaundice & icteric sclera - hemolytic anemia  If destruction exceeds ability to make new RBCs: anemia
NORMAL HEMOGLOBIN IN NEWBORNS ❏ Frontal Bossing - seen in thalassemia B. HYPOPROLIVERATIVE ANEMIAS
❏ Preterm -anemic or low Hgb ❏ Maxillary hyperplasia - seen in thalassemia  Etiology usually localizes to bone marrow
1,000-1,200 grams = earlier signs Rationale: Thalassemia - the bone marrow compensates and  Generally present with symptomatic anemia
1,500-2,000 grams = late signs frontal bone is active and expands NOTES:
RULE OF THUMB TO DECIDE IF CHILD IS ANEMIC ❏ Petechiae - platelet problem ӿ Always use absolute reticulocyte count = (RBC x % of retic)
❏ Tri phalangeal thumb - seen in diamond blackfan anemia ӿ Retic % is frequently overestimated
❏ Lower limit of normal for HEMOGLOBIN
LABORATORY MANIFESTATIONS OF ANEMIA ӿ Percentage should only be taken in context of “whole” RBC
11 + 0.1 x (age in years)
Example - for a 3 y/o: 11+0.3x3 = 11.3 g/dL CBC Example: retic = 1% would not flag as abnormal
❏ Most commonly performed test in medicine If hgb is 6 g/dL, a 1% retic is inappropriate response to anemia
❏ Lower limit of normal for MCV ӿ Stained with new methylene blue stain
70 x (age in years) ❏ First performed in 1960s ӿ Wright’s stain - polychromasia
Example - for a 3 y/o: 70 + 3 = 73 fl ❏ Fully automated (10% on blood smears are manual) Morphologic
PHYSIOLOGIC ADAPTATION ❏ Assessment of RBCs, WBCs, Platelets A. MICROCYTIC ANEMIA
❏ Increased heart rate = easy fatigability ❏ Composed of:  Iron deficiency, lead poisoning, anemia of inflammation or
❏ Increased stroked volume WBC count, RBC count, Hgb/Hb concentrations, Hct, MCV, MCH, chronic diseases, thalassemia
MCHC, RDW, ANC, Platelet count, MPV  Red cells - increase in central pallor, lymphocytes are bland
❏ Vasodilation = compensatory of increase SV
Differentials: Eosino, Baso, Neutrophils, Monocytes, Lymphocytes
❏ Decreased oxygen affinity (shift to the right) Iron deficiency Thalassemias Inflammation
❏ Hgb, ANC & Platelet count is important Hb Low Low Low
Enhances 0xygen delivery to the tissues
❏ For differentials: Eosino, Baso, Neutrophils, Monocytes,
MCV Low Low Normal/low
Increased temp, 2-3 DPG & hydrogen
Lymphocytes
❏ Decompensated anemia: adaptation is not capable to counteract RDW High Normal Normal
❏ MCV - indicates average size of red cells
- needs blood transfusion Ferritin Low Normal High
(micro,macro,normo)
Retic Low Normal/low Low
❏ RDW - indicates variation in size of red cells
❏ MPV - indicates average size of platelets
Compiled by: JMB
RDW - distribution of red cell, high in iron deficiency because bone produces
diff. kinds of red cells (disparity); Thalassemia & inflammation has normal
because marrow produces equal amount
Ferritin - storage of iron,in Iron deficiency it is low while in inflammation it is
high because increase in acute phase reactant of ferritin

SPECIFIC DISEASES B. Diamond-Blackfan Anemia

B. MACROCYTIC ANEMIA
A. Iron Deficiency Anemia  Normocytic, hypoproliferative
 Not common in pediatric patients
 Highest prevalence among 1-3 year old who are poor  Inherited form of red cell aplasia (autosomal dominant)
 B12, folate deficiency
 Low income infants and toddlers (12-36 months)  1/2 of patients with congenital abnormalities
 Large red cell than lymphocytes seen in smear
 7-15% prevalence of iron deficiency w/o anemia Short stature, abnormalities involving head, upper limbs, heart, GUT
 Most common cause is drug use:  Abnormalities of the bone marrow
- impaired folic acid absorption (methotrexate, mercatopurine  1-4% prevalence of iron deficiency w/ anemia
Marked erythroid hypoplasia or total erythroid aplasia
Phenytoin, bactrim)  Teenage girls (menstruation), elderly Normal myeloid & megakaryotcytic lineages
- impaired DNA synthesis (AZT, hydroxyurea)  Others: vegetarians, vegans, pregnant or breastfeeding CONGENITAL ABNORMALITIES - DBAR update
 Myelodysplasia women, GI diseases or bariatric ANOMALY FREQUENCY
 Hypothyroidism IRON HOMEOSTASIS: Head, face, palate 24%
 Fanconi anemia Our body contains 3.5 grams of iron Hypertelorism, cleft or high-arched palate
 Diamond blackfan anemia 1-2 milligrams is absorbed in 10mg/day consumed Microcephaly
 Chronic alcohol use (adolescence) 1-2 milligrams is also lost by desquamation of epithelial cells of GIT & mens Musculoskeletal 21%
Excessive cow’s milk intake predisposes to iron deficiency because: Triphalangeal, duplex/bifid thumb, etc.
 Liver disease Renal, Genitourinary 19%
- contains <1 mg/L of Fe
C. NORMOCYTIC ANEMIA - Iron in cows milk is poorly absorbed (less bioavailability) Absent or horseshoe kidney, hypospadias
 Anemia of chronic inflammation - Leads to decreased intake of other foods Cardiopilmonary 15%
 Diamond blackfan anemia - Causes no-allergic allergic inflammation & damage to intestinal mucosa (bleed) VSD, ASD, coarctation
 Fanconi anemia - Breastmilk is high bioavailability DIAGNOSIS of DBA
Normally, intact, transport & erythron iron ❏ Age less than 1 year
 Hereditary spherocytosis (abnormality in membranes)
 Hereditary Elliptocytosis ❏ Macrocytic anemia with no other signicant cytopenia
❏ Reticulocytopenia
❏ Normal marrow callularity with paucity of erythroid precursors
❏ Major criteria: Gene mutation (classical DBA), positive family history
❏ Minor criteria: elevated erythrocyte ADA,
congenial anomalies (classical DBA)
TREATMENT OF DBA
❏ Corticosteroids
80% initially responsive, 37% long-term
Red cells is microcytic hypochromic in iron deficiency ❏ Chronic PRBC transfusions
Smears: increase central pallor, tear drop cell, ovalocytes = ↑ RDW During 1st yr of life, 31% long-term
TREATMENT of Iron Deficiency: ❏ No treatment
1. Identify & treat or eliminate causes Never treated ~4%, off therapy ~20%
(dietary counseling is critical but does not treat deficiency) ❏ Hematopoietic stem cell transplantation
2. Transfuse if clinically indicated (if decompensated = clinical signs) If steroid-resistant, severe iron overload
3. Adminiter 3-6 mg/kg/day of elemental iron (2-3 mos or more) Siblings HSCT ~70% survival
Alternative HSCT 20-40% survival

Compiled by: JMB

 ❏ Aplastic crisis
❏ Gallstones (splenectomy decreases risk)

C. Fanconi Anemia D. Hereditary Spherocytosis G. Sickle Cell Anemia

 Macrocytic,rmocytic, hypoproliferative  Inherited hemolytic anemia  Refer to group of blood disorders with predominance of HbS
 Characterized by 2/3 congenital abnormalities, progressive  Most common RBC membrane defect  Inherited (affecting 1 in 400 African-American live births)
bone marrow failure, increased cancer predisposition (MDS,  1 in 5,00 in north european descent  Includes several different genotypes: HbSS, HbSC, HbS/beta-
AML, solid tumors)  Spherocytes has no central pallor thalassemia, HbS/other
 1 per 100,000 live births: most common inherited BMF syndrome  Clinical phenotype:  Sickle cell genotypes:
 Atleast 15 diff. Genes identified: Majority are AR, few x-linked HbSS HbSC
CLINICAL PRESENTATION of FA Common, severe milder form
❏ Ahort stature, microcephaly, elfin face Hb is 6-9 gm/dL Hb is 8-12 gm/dL
❏ Thumbs up & radius anomalies Sicked RBC, polychromasia Target cells
Thenar hypoplasia  CBC & peripheral smear: Anemia, microcytosis, elevated
Clinodactyly of 5th digit
WBC & platelets
Syndactyly
Hyperextensible thumbs
Absence or hypoplastic radius
❏ Renal and ureter abnormalities
❏ Hypogonadism TREATMENT OF HS
❏ Gastrointestinal abnormalities ❏ Supportive Care
❏ Hearing deficit ❏ Folic acid
❏ 1/3 only no physical abnormalities ❏ Transfusion: <30% requires transfusion
DISEASE COURSE of FA ❏ Operative splenectomy (open vs. Laparoscopic; total vs. Partial)
❏ Variable
❏ If no treatment will lead to pancytopenia E. Hereditary Elliptocytosis
Transfusion dependent in 5-10 years  More common in areas of enedemic malaria
❏ Myelodysplastic syndrome, acute myeloid leukemia  Predominantly autosomal dominant inheritance
Cumulative incidence of 40% for MDS, 10% for AML by age 50  Mutations: alpha-spectrin 65% & beta-spectrin 30%
Chromosome 7 & 3q abonormalities with poor prognosis  Presence of elliptocytes
❏ Solid tumors: squameous cell carcinoma (head and neck), F. Hereditary Pyropoikylocytosis
GUT, liver  Relative of HE but most severe form
❏ Median age of survival 20 years (25% live beyond 31 yr old)  Defect of spectrin synthesis
TREATMENT OF FA  Thermal sensitivity: erythrocytes fragment at 45-46C
❏ Hematologic support, transfusions (normal is 49C)
❏ Androgens  Presence of Pyropoikilocytes
About 50% patient improve, median prolongation by 2 years
DISEASE COURSE of Pyropoikylocytosis
Relapse is inevitable TREATMENT of sickle cell
Associated with toxicity, virilization ❏ Variable (silent carriers/nonhemolytic: severe hemolysis)
❏ Signs and symptoms is similar to HS  Hydroxyurea
Increased risk of hepatic adenoma, carcinomas
Osmotic fragility is abnormal  Induces production of fetal hemoglobin
❏ HSCT
Markers of hemolysis LDH, bili & elevated reticulocyte  Beneficial effects: Red cell are larger, less sickling, less
Allogeneic HSCT: HLA matched donor
Alternative donor BMT Smear is diagnostic inflammation
❏ Treatment: supportive care & rarely splenectomy  Decreases number of painful crises, acute chest,
HEMOLYTIC ANEMIA COMPLICATIONS hospitalization, transfusions and improves mortality
❏ Neonatal jaundice
❏ Hemolytic crisis
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Compiled by: JMB
Compiled by: JMB
 ONCOLOGY GERMLINE MUTATIONS ❏ NEWBORN SCREENING upto 6 months
❏ The First Hit  High risk if birth weight <1,500 grams
RETINOBLASTOMA  95% submicroscopic:  External eye examination
 75-80% point mutations  Vision assessment: fix and follow
❏ Cancer of the young patients
 15-20% detected by southern blot  Eye movements
 3-5% recognized by cytogenetics: 13 q-syndrome  Pupillary response
INCIDENCE  RB1 = 180 kb (27 exons)  Simultaneous red reflex
❏ Retinoblastoma is 14% common in infant & 3% in children  Site: coding region of exons 33,8,18,19; 200+ mutations identified ❏ NEWBORN SCREENING 6 month to 3 years
 TYPES: 70% nonsense & frameshift; 30% Splicing  High risk: developmental delay, neurologic deficits, systemic
 Splice mutation is diagnose late than nonsense/frameshift disease associated with eye abnormalities
 CpG dinucleotides: hot spots
 Red flags: infant who does not recognize faces/objects, and
 Common in paternal allele:
 Exposure to welding fumes, metal industry, smoking or or fix & follow, hx of tearing or eye deviation
xray/radiation exposures  Test for visual acuity, corneal light reflex, cover-uncover
 Common in indians, blacks than white, philippines (sporadic) test, ophthalmoscopy
TREATMENT
❏ Unilateral retinoblastoma
BIOLOGY  Usually advanced disease
❏ A. Knudson - computes the possibility of retinoblastoma in 1971  Endophytic growth - vitreous
 He published two-hit hypothesis, therefroe in order the child to  Exophytic growth - retinal detachment
develop this - there should be a two events in the genes
 Surgery - performed by expert surgeon
 Unilateral - circular curve; Bilateral - linear curve
 Child born with genetic abnormalities - then develops genetic  Removal of long section of optic nerve
❏ The Second Hit  Placement of orbital implant (hydroxyapatite)
accidents = cancer
 Retinoblastoma there is something missing  Occurs spontaneously at a rate of 1:1000  Histopathological exam
 If baby is born with germline mutations, will have more  75%+ is often chromosomal in nature (somatic/acquired):  Choroid involvement with blood stream access leads
predisposition of somatic abnormalities (chromosomal) exposure to  50% mitotic recombinations to metastasis
environment = BILATERAL  40% nondisjunction  Enucleation alone: cure 80-90% patients
 If baby was born without germline mutations, will need 2 genetic  10% deletions  5% patients: extraorbital disease
accidents (somatic/acquired) = UNILATERAL  More sensitive to environmental factors: xray >2,000x  10-15% patients: intermediate risk
❏ Retinoblastoma gene was discovered in 1986 HISTOPATHOLOGIC RISK FACTORS MORTALITY AFTER ENUCLEATION
 Is a brake or regulator of cell cycle
HISTOLOGY MORTALITY CT
 Rb1 gene combines with transcriptor factor (E2F) which disables to
block the cell to progress into S phase LEUKORIA Ocular nerve pre-laminar 0-29% -
1. If inactivated by phosphorylation (kinases) there will be no more ❏ Greek word means ‘White pupil” Ocular nerve post-laminar 13-69% ++
brake in cell cycle: Cell will continue to proliferate ❏ AAP guidelines: All neonates, infants and children should Ocular nerve cut end 50-81% ++++
2. If mutation occurs, the gene is absent and no break in cell cycle: have an examination of the red reflex of the eyes performed Choroid 11-81% -/+++
tumor grows (progression) Ocular nerve & choroid 33-75% +++
by a pediatrician or other primary care clinician trained in
❏ Two clinical forms Anterior chamber 20-80% ++
this examination technique before discharge from neonatal
1. Hereditary, bilateral, multifocal (40%) INTERMEDIATE-RISK RETINOBLASTOMA
nursery and during all subsequent routine health
 Germline mutation of RB1 ❏ Deep choroidal disease
 25% cases: inherited from carrier parents supervision visits
❏ RED REFLEX TEST: ❏ Ciliary body, iris or anterior chamber
 75% cases: de novo mutation by early embryogenesis
 Hold a direct ophthalmoscope close to the examiner’s eye with ❏ Optic nerve: beyond lamina cribrosa?
 Median time to diagnosis: 14-16 months
ophthalmoscope lens power set at “0” ❏ Optic nerve involvement pre-laminar only associated
2. Non-hereditary, unilateral, or unifocal (60%)
 Mutation of both Alleles in a somatic cell  In a darkened room, the ophthalmoscope light should projected with increased risk if associated with other risks
 Median time to diagnosis: 29-30 months onto both eyes of the child simultaneously from approximately 18 ❏ Involvement of central retinal vessel or subarachnoid
inches away should be considered high-risk (metastatic
 Normally, red reflex emanate from both eyes & be symmetric METASTATIC RETINOBLASTOMA
❏ Retinoblastoma cells in bone marrow

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RB1+/RB1-
❏ Retinoblastoma is just the beginning
❏ Radiation affects the chemotherapy and may develops
2nd malignancy
INSIDE RADIATION FIELD OUTSIDE RADIATION FIELD
Osteosarcoma Ostesarcoma
Fibrous histiocytoma Renal cell carcinoma
Leiomyosarcoma Erwing’s sarcoma
Angiosarcoma Carcinoma of tongue
Rhabdomyosarcoma Medulloblastoma
PNET Malignant melanoma
Meningioma Hodgkin’s disease
Glioma

MORTALITY ASSOCIATED TO 2ND NEOPLASM

❏ Higher if bilateral than unilateral
❏ Radiation is a risk factor (60%)
❏ Without radiation (30%)
❏ AVOID RADIATION IS PREVENTABLE
❏ After radiation (XRT) hourglass deformity and
hypoplastic orbits may develop

CURRENT APPROACH TO INTRAOCULAR RETINOBLASTOMA

❏ Focal treatments of radiotherapy & enucleation,
cytoreduction

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 PEDIATRIC LEUKEMIA ❏ Leukemia is the cancer of the blood PATHOBIOLOGY
❏ Arises from the bone marrow ❏ First event
BACKGROUND ❏ Represents a clonal explansion and arrest in the maturation  Most common: initiation
CANCER DISTRIBUTION BY AGE of normal myeloid or lymphoid hematopoeisis  Occurs at birth
❏ 0-14 years old: leukemia, brain tumors, lymphomas ❏ Normal Bone Marrow Function:  Chromosomal translocation hyperdiploidy
❏ 15-19 years old: Lymphomas, leukemia ❏ Red marrow - spongy bone that produces  Present with abnormalities at birth but no leukemia, and
hematopoietic cells (stem cells, RBC,WBC, platelets) once triggered then it will develop (deletion or mutation)
CHILD VS. ADULT
❏ In Hematopoietic system, all blood originates in the stem cells ❏ Second event
❏ Children; ALL, AML and differentiate in myeloid or lymphoid  2-15 years old
❏ Adults: AML, lymphomas ❏ Myeloid stem cells - RBC, platelets, Myeloblasts  Rare: transition to ALL/AML
DEFINITION (eosinophils, neutrophils, granulocytes, basophils)  Gene deletion or mutation
❏ Cancer of the blood ❏ Lymphoid stem cells - lymphoblast (B, T lymphocytes & NOTE: NO WAY TO PREVENT LEUKEMIA
❏ 3,250 children diagnosed per year in USA natural killer cell) MANIFESTATIONS
❏ Two main groups of leukemia: ETIOLOGY ❏ Systemic: weight loss, fever, frequent infections
 Acute Lymphoblastic Leukemia (ALL) - 80% most common ❏ Unknown ❏ Lungs: easy shortness of breath
but good prognosis ❏ Complex interplays between genes, environment and ❏ Muscular: weakness
 Acute Myeloid Leukemia (AML) - 20% less common but poor chance events ❏ Bones or joints: Pain or tenderness
prognosis ❏ Certain factors that increases the risks ❏ Psychological: fatgue & loss of appetite
❏ There has been steady increase of 1% per year in
❏ Lymph nodes: swelling
incidence of ALL for 25 years (migration of hispanics) RISK FACTORS ❏ Spleen or liver: enlargement
EPIDEMIOLOGY ❏ Constitutional/Genetic ❏ Skin: night sweats, easy bleeding & bruising, purplish
❏ Hispanics has the highest incidence  Down syndrome (10-20x higher, 600x higher in patches or spots
❏ Philippines: megakaryoblastic type) ❏ CLINICAL PRESENTATIONS:
 0-19 y/o - 5030 cases  Fanconi anemia  Hepatomegaly
 ALL - 2637 cases; AML - 1151 cases  Neurofibromatosis  Enlarged lymph nodes
 Peak age - 1 to 4 years old  Ataxia-telangiectasia  Painless lymphadenopathy (Hodgkin)
❏ By mean annual per capita gross national income:  Li-Fraumeni syndrome  Nodal enlargement in mediastinum (chest x-ray)
Norway, switzerland, denmark due to access to  Polymorphisms of xenobiotic metabolizing enzymes  May lead to tracheal compression & obstruction =
 High birth weight respiratory arrest
diagnosis = referral arrival and evaluation
 Familial aggregation: concordance in twins  Gum hyperplasia, macula & retina
❏ Philippines is 45% incidence
❏ Environmental  Genitourinary tract involvement:
❏ Estimated cure rates in selected countries:
 Ionization radiation  Painless enlargement of testis (20%)
 High-income country cure rate = (100% dx access) x  Non-ionizing radiation (EMF)  Risk factors: T-cell ALL, leukocytosis, mediastinal mass,
(100% tx access) x (80% EFS) = 80%  Chemicals moderate hepatosplenomegaly or lymphadenopathy,
 Pesticides thrombocytopenia (<30,000)
 Alcohol consumption  Skin involvement: Congenital leukemia, leukemia cutis
 Cigarette smoking
 Selected infections
 HPV - cervical cancer
 HIV
 Epstein barr virus - Burkit’s lymphoma

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DIAGNOSIS WHAT IS A BLAST? - immature white blood cells
❏ LABORATORY FEATURES 1. MORPHOLOGY OF BLAST
WBC count ❏ LYMPHOBLASTS
<10,000 53%  Round nucleus
 Homogenous chromatin
10,000-49,000 30%
 Indistinct nucleoli
>50,000 17%  High Nucleus/Cytoplasm
Hgb (g/dl) normocytic/normochromic  No granules
<7 43% ❏ MYELOBLASTS
7-11 45%  Spongy chromatin 3. IMMUNOPHENOTYPE OF BLAST
>11 12%  Low N/C ANTIGEN LINEAGE
Platelets (mm)  Granules CD45 All WBCs
 Auer rods CD19 B-cell
20,000 28%
cCD79a B-cell
20-99,000 47% CD7 T-cell
>100,000 25% CLASSIFICATIONS:
ACUTE LYMPHOBLASTIC LEUKEMIA cCD3 T-cells
❏ The most common laboratory abnormality is ANEMIA MPO Myeloid/monocytic
 ALL, L1 - small blasts, dark nuclear chromatin, small
& THROMBOCYTOPENIA grains cytoplasm CD13 Myeloid/monocytic
❏ Hyperleukocytosis - high WBC count (>500,000)  ALL, L2 -Larger more heterogenous CD33 Myeloid/monocytic
 ALL, L3 (burkitt) -Really large lymphoma cells, clear CD117 Myeloid/monocytic/megakaryocytic
DIAGNOSIS is base on morphology, FISH, Cytogenetics, flow punched out vacoules CD41a megakaryocytic
cytometry, Next-generation sequencing-based mutation profiling ACUTE MYELOID LEUKEMIA CD235a (GPA) Erythoid
❏ Bone marrow aspiration & smear  AML, M0/M1 - minimally differentiated/without
 Acute Myeloid Leukemia - “auer rod” is the pathognomonic maturation 4. CYTOGENETICS OF BLAST (prognostic significance)
which is an eosinophilic needlelike inclusion in the  AML, M2 - with maturation type  Tel-AML 2 fusion gene -sensitive to chemotherapy (ALL)
cytoplasm  AML, M3 - promyelocytic type prone to DIC  BCR-ABL fusion gene - bad prognosis
 Acute Lymphoblastic Leukemia- monotonous population of (Disseminated Intravascular Coagulation)  EZA-PBX1 fusion gene
immature cells; Hyperleukocytosis  AML, M6 a/b - erythroleukemia (RBS & WBC  MLL gene rearrangement - bad prognosis
involvement); binucleus, disblastoid cells, myeloid- TREATMENT
appearing blast ❏ Mainstay of treatment is chemotherapy
 AML, M7 - megakaryoblastic (common in down ❏ Should begin within days of diagnosis
syndrome); blebs on surface plasma ❏ Good supportive care
MIXED-LINEAGE LEUKEMIAS (in this cytochemical is next step) ❏ Goals:
 Acute bilineal leukemia  To induce a clinical and hematologic remission
 Acute biphenotypic leukemia  To maintain remission by systemic chemotherapy and
2. CYTOCHEMICAL OF BLAST (lymphoid) prophylactic CNS therapy
 Periodic Acid Schiff (PAS) is positive = as coarse granules or  To treat the complications of therapy and of the disease
blocks in a variable number of cells (seen in LYMPHOBLAST) ❏ Treatment for boys: 3 years
 Myelo peroxidase (seen in MYELOBLAST; monocytic or
❏ Treatment for girls: 2 years
myeloid)
❏ Divided into different phases and by spinal tap to
 T-cell ALL + Acid phosphatase
neutralize into the brain
PRINCIPLES
❏ Acute lymphoblastic leukemia
 Intensive multi-agent chemotherapy (6-12 months)
 Central Nervous System directed-therapy
 Less intensive maintenance (2.5-3 years)
 Bone marrow transplantation (5%)
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 ❏ Acute Myeloid leukemia
 Intensive cycles of cytarabine or anthracycline
chemotherapy (4 or 5)
 Central Nervous System directed-therapy
 Bone marrow transplantation (30%)

GOOD PROGNOSTIC FACTORS

❏ Age 1-10 years old
❏ WBC count <50,000
❏ Pre-B immunophenotype
❏ DNA index >1.16
❏ Hyperdiploid - cell is continuously multiplying good
indicator for chemotherapy
❏ T(12:21)(TEL/AML1 fusion)
❏ No CNS disease
❏ Early response to treatment

IMPROVING CURE RATES

❏ Refinement of current therapy
 Maximum efficacy, minimum toxicity
❏ Individualization of dosage
❏ Improving risk classification
❏ Development of new cancer drugs
❏ Understanding the mechanism of disease
❏ Extend the benefits to all children of the world
❏ Importance of research & individualization of therapy

Principle of chemotherapy - destroys the normal cells, limited only

for treatment
Principle of immunotherapy - Activate the cytotoxic T-cells or natural
killer cells (normally it is inactivate)
Bone marrow transplant - rescue the overtherapy of chemo
KEY POINTS
❏ Leukemia is the most common cancer in children
❏ Biology and incidence is different from an adult
❏ Prevalence and survival is related to economic
❏ Cause is unknown but it is an interplay of genes and
environment
❏ Great mimicker
❏ Diagnosis is by demonstration and categorization of the
blasts
❏ Mainstay of treatment is chemotherapy
❏ Some requires bone marrow transplantation

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