BGD Case 1

Temew, Kevin C.
Templo, Allain Joseph S.
Teoxon, Jane H.
Terania, Lorenzo C.
Timbol, Edith Mari G.

Salient Features
Subjective

46 y/o F
Profuse menstrual flow
On and off fever
Easy bruisability
Shortness of breath
(-) headache, bone pain,
nausea, vomiting, melena,
hematochezia, dysuria,
hematuria

Objective

BP: 100/70
PR: 100/min
RR: 24/min
Pallor
(-) jaundice, cervical
lymphadenopathy
Spleen and liver are not
palpable
Temew, Kevin C.

Salient Features
CBC:
Hb: 7.2 g/dL
Hct: 0.21
WBC: 245,000/cu.mm
Neutrophils: 25%
Lymphocytes: 15%
Blasts: 55%

PC: 65,000/cu.mm

Temew, Kevin C.

Assessment
Anemia
Leukocytosis
Thrombocytopenia

Tachypnea
Pallor
Hb: 7.2 /dL
Hct: 0.21

WBC: 245,000/cu.
mm
*Blasts: 55%

Profuse menstrual
flow
Easy bruisability
PC: 65,000/cu. mm
Temew, Kevin C.

Differential Diagnosis
Acute Myelogenous Leukemia
Acute Lymphoid Leukemia

Temew, Kevin C.

Primary diagnosis

Acute Myelogenous Leukemia

Temew, Kevin C.

Clinical Manifestations
SYMPTOMS:
Non-specific symptoms
Fatigue or weakness
Anorexia & Weight loss
Headache
Bone Pain
Bleeding and Easy Bruising
Fever with or without an identifiable infection

Clinical Manifestations
PHYSICAL FINDINGS:
Splenomegaly
Hepatomegaly
Lymphadenopathy
Sternal Tenderness
Evidence of Infection
Hemorrhage

HEMATOLOGIC FINDINGS
Normocytic Normochromic Anemia
Dec. Erythropoiesis
Median presenting Leukocyte: 15000/uL
<5% No detectable Leukemic cells
Poor Neutrophil Function
Platelet <100,000/uL in 75% of patients; <25000/uL in
25%

Complications
Leukostasis
Disseminated Intravascular Coagulation
Chloroma
Tumor Lysis Syndrome
Infections

Laboratory Work ups

Teoxon, Jane H.

CBC

Normal Value

Patients CBC

WBC

4.0-11.0

245,000/mm3 (245)

RBC

4.4-5.90

HGB

F: 11.6-14.6

7.2 g/dL

HCT

F: 33-47%

0.21(21%)

MCV

80-99

MCH

27-34

MCHC

31-36

RDW

11-16

PLT

150-450

MPV

9.0-12.7

NEUTR%

55-70

LYMPH%
16.0-48.0
Bone Marrow biopsy
MONO%
2.0-14.0
Blast
EOS%
0.0-4.0

65,000.mm3 (65)

25%

4%
55%
1%

>20%
Acute leukemia
N
N

Teoxon, Jane H.

Teoxon, Jane H.
Delicate nuclear
chromatin
Prominent nucleoli
Fine azurophilic
granules in the
cytoplasm (auer rods)
At least 20% myeloid
blasts

More condensed
chromatin
less conspicuous
nucleoli
smaller amounts of
cytoplasm that usually
lacks granules
B

AM
L
ALL

Teoxon, Jane H.

IMMUNOPHENOTYPING
Immunohistochemistry
Can use fixed/archived tissue
Architectural ad cytologic correlation
Can assess nonviable ghost cells
Longer turnaround time (hours to days)
Semiquantitave results
High background staining for Ig light
chains
Usually limited to a single antibody per
slide
Fewer ab available
Easily transported to reference lab for
special studies

Need fresh cells or tissue

Limited morphologic correlation
Cannot assess nonviable cells
Short turnaround time (min to hrs)
Less subj result interpretation
Quantitative results
Good to detect Ig light-chain reaction
Multiple ab/fluorochromes per test
Greater ab selection
Loss of viability issues with transport

Acute Leukemia Immunohistochemistry; a systematic diagnostic approach by Randall J. Olsen, MD, et al., 2008

Cytogenetics
Cytogenetic analysis
Karyotypic aberrations are detected in 50 to 70% of cases with
standard techniques and up to 90% with high resolution
banding.
1) de novo in adults
t(8;21) inv(16) and t(15;17)
2) AMLs following MDS or exposure to DNA-damaging
agents (chemo/radiotherapy)
del/monosomies of (5 and 7) usually lack translocation
3) AML arising after treatment of topoisomerase II
inhibitors which is strogly associated with MLL gene on
chromosome 11q23.

Teoxon, Jane H.

Sources:
Harrisons Principles of Internal Medicine, 19th ed
Robbins and Cotran Pathologic Basis of Disease, 9th ed
Pubmed Jounal: Acute Leukemia Immunohistochemistry; A
Systematic Diagnostic Approach by Randall J. Olsen, MD, et al.,
2008

TREATMENT OF AML

GOALS OF THERAPY
To induce complete remission
Restoration of normal blood cell levels

To prevent relapse

TERANIA, Lorenzo Jr. C 1

2 Phases of Treatment
Induction chemotherapy
Post remission therapy

TERANIA, Lorenzo Jr. C 2

GOAL OF INDUCTION THERAPY

To induce complete remission (CR)
Restoration of normal bone marrow function
Recovery of normal bone marrow cellularity with:
fewer than 5% blast cells
Recovery of peripheral blood counts with:
neutrophil count of >/=1000/uL
platelet count of >/=100,000/uL

TERANIA, Lorenzo Jr. C 3

Standard regimen
(7 + 3) Regimen
Cytarabine, 100-200 mg/m2 IV for 7 days
Anthracycline, IV for 3 days (Day 1, 2, & 3)
Daunorubicin, 60-90 mg/m2
or

Idarubicin, 12 mg/m2

If there is persistence of leukemia,

Retreat with the same agents (5 + 2)
Daunorubicin

TERANIA, Lorenzo Jr. C 4

Postremission therapy
GOAL:
To prevent relapse and prolong survival
Includes:
Chemotherapy
Cytarabine
Hematopoietic stem cell transplantation (HSCT)
Autologous
Allogeneic
TERANIA, Lorenzo Jr. C 5

Supportive treatment
Blood transfusion
Maintain:
platelet count of >/=10,000/uL
RBC count >80 g/L
Antibacterial/antifungal drugs
Can given if there is:
neutropenia (as prophylaxis)
fever (empiric antibiotic therapy)

TERANIA, Lorenzo Jr. C 6

Prognosis
TIMBOL, Edith Mari G.

Prognosis
Prognostic factors
Age at diagnosis (Advanced age)

Co-existing abnormalities
More resistant AML
Antecedent hematologic disorders
Expression of MDR1 efflux pump
Less favorable cytogenetic abnormalities

Low performance status

High presenting leukocyte count (>100,000/ul)
Cytogenetics and/or molecular aberrations
TIMBOL, Edith Mari G.

Prognosis
Cytogenetics
o t(15;17) very good prognosis (85% cured)
o t(8;21) and inv(16) good prognosis (55% cured)
o no cytogenetic abnormalities intermediate (40%)
o complex karyotype, t(6;9), inv(3) or -7 very poor prognosis

TIMBOL, Edith Mari G.

Prognosis
Molecular aberrations
o Favorable outcome NPM1 and CEBPA mutations
o Poor outcome - FLT3 ITD
o Receptor Tyrosine Kinases
o Transciption Factors
o Epigenetic Modifiers
o Deregulated Genes
o Deregulated MicroRNAs

TIMBOL, Edith Mari G.

Harrisons Principles of Internal Medicine

19th Edition

TIMBOL, Edith Mari G.

Prognosis
Complete remission better outcome and longer
survival
o Blood neutrophil count 1000/L
o Platelet count 100,000/L
o Absent circulating blasts
o Bone marrow < 5% blasts
o Auer rods absent
o Absent Extramedullary Leukemia

TIMBOL, Edith Mari G.