CASE 3

CASE 3
• เด็ กห ญิ งอา ยุ 9 ปี มี อา การ อ่อน เพล ีย มา 2 สัปดา ห์

• 2 สัปดา ห์ก่ อนมา โร งพย าบา ล ผู้ ป่ ว ยมี อา กา รอ่ อนเ พลีย
มา รดา สั งเก ตว่ า ผู ้ ป่ วยซีด จึงพา ไปต รวจที่อน ามัย
แพทย์ บอก ว่า ผู้ป่วยเ ป็ น โร คโล หิตจา ง ให ้ ย าบำา รุ งเ ลือดมา กิ น

• 3 วัน ก่อน มา โรง พยา บา ล ผ ู้ป่ว ยมี อา กา รอ่อน เพล ียมา กข ึ้ น

ไปโร งเ รี ยน ไม่ไ หว มี จุดแ ดง ขึ้น ตามตัว และแขนข า
มา รดา จึง พา มา โรง พยา บา ล

• ปฏิ เสธโร คประจ ำา ตัว ไม่ ม ี ถ่า ยดำา ผู ้ป่ว ยยั งไ ม่ ม ี ป ระจำา เดือน
Pertinent Subjective Data

• อ่อ นเพ ลี ย ซี ด
• จุ ด แด งขึ้ นตาม ตัวแ ละแ ขน ขา
• ไม ่ มี ถ่ า ยดำา
• ยัง ไม ่ม ี ประจ ำา เดื อน
• ปฏิเ สธโ รคป ระจ ำา ตั ว
 2 สั ปดา ห์ ที่ ผ่า นมา ซีด อ่อน เพล ี ย

แพท ย์สง สั ยโลหิตจ าง

ให ้ย าบำา รุง เล ื อด

3
อ่อ นเพล ี ย มากขึ้ น + จุด แดง
วั นก่อ นม าโรงพ ยา บา ล
ขึ ้นตา มตั วแล ะแขนขา

ประ วัต ิ
-ไม ่ ม ี โร คป ระจ ำา ตั ว
-ไม ่ ม ี ถ่ ายดำา
-ไม ่ ม ี ปร ะจ ำา เดื อน
 Anemia

Anemia is defined as a reduction of the RBC

volume or hemoglobin concentration below the
range of value occuring in healthy persons.

Richard E. Behrman, Robert M. Kliegman, Hal B. Jenson. Nelson textbook of pediatrics. 16th edition. W.B.Saunders company. Pennsylvania. 2000
 Minimum of Hct and Hb
(WHO)
Ages Hb (g/dL) Hct (%)

6 mo – 6 yr 11 33

6 – 14 yr 12 36

Male 14 yr up 13 39

Female 14 yr up 12 36

Pregnancy 11 33
 Causes of anemia

• Blood loss (Acute and chronic)

• Excessive destruction of RBCs

• Decreased production of RBCs

 Causes of anemia

 Blood loss
• Acute
– Trauma, Nosebleeds, Obstetrical complication, etc.

• Chronic
– GI bleeding, Vaginal bleeding
 Causes of anemia
 Excessive destruction of RBCs
• Hereditary
– Thalassemia, G6PD def, PK def, spherocytosis,
elliptocytosis, HbS, etc.

• Aquired
– alloantibodies, ( ex. incompat. blood transfusion)
– Autoantibodies ( ex. SLE, AIHA, TTP )
– Drug induced antibodies ex. penicillin
– Infections, ( ex. malaria )
 Causes of anemia
 Decreased Production of RBCs
• Nutritional deficiency (inadequate intake)
o Iron, B12, folate deficiency anemia

• Defective absorption: Pernicious anemia

• Chronic kidney disease : Decrease EPO

• Bone Marrow Failure

o Congenital and acquired aplastic anemia
o Congenital and acquired pure red cell anemia
o Infiltrative (Leukemia, lymphoma)
o Myelofibrosis and osteopetrosis
Common causes of anemia in children

• Iron deficiency (most common)

• Thalassemia
• Chronic disease
• Vitamin B12 deficiency
• Folate deficiency
• Bone marrow failure
• G6PD deficiency
 Bleeding Disorders
Primary hemostasis Secondary hemostasis
(Platelet and vessel) (Coagulation factor)

Signs Petechiae, Large ecchymosis,

Purpura, Hematoma
Small ecchymosis

Location Skin, Muscle,

Mucous membrane Intra-articular,
Deep connective tissue

Duration Immediate bleeding Delayed bleeding

Response when press on Stop bleeding Continue bleeding

Petechiae & Purpura Ecchymosis

Hematoma
Differential Diagnosis 1
Differential Diagnosis From History

 Blood loss
• Acute
– Trauma, Nosebleeds, Obstetrical complication, etc.
• Chronic
– GI bleeding, Vaginal bleeding

No melena and history of blood loss

Differential Diagnosis From History
 Excessive destruction of RBCs
• Hereditary
o Thalassemia, G6PD def, PK def, spherocytosis,
elliptocytosis, HbS, etc.
ซัก ประวัต ิค รอ บครัวเ พิ ่ม
• Aquired เติม
o Alloantibodies, (ex; incompatible blood transfusion)
No history
o Autoantibodies ( ex; SLE, AIHA, TTP )

o Drug induced antibodies ; penicillin No drug use

o Infections ( ex ; malaria ) No history of camping

Physical Examination : Jaundice, Dark urine

Differential Diagnosis From History
 Decreased Production of RBCs
• Nutritional deficiency (inadequate intake)
o Iron, B12, folate deficiency anemia
• Defective absorption:
o Pernicious anemia No history of ileectomy

• Chronic kidney disease : Decrease EPO No history

ซักป ระวั ติเ พิ่ มเติ ม : Di et ary beha vior

Phys ical E xami nat ion ; Glo ssit is ,Ko ilo nych ia (Iro n D ef. a nemia )
,Pe rip hera l Ne uro pathy
 glossitis

Koilonychia - spoon shaped nail

Differential Diagnosis From History

 Decreased Production of RBCs

• Bone Marrow Failure
o Congenital and acquired aplastic anemia
o Congenital and acquired pure red cell anemia
o Infiltrative (Leukemia, lymphoma, Myelofibrosis)
o osteopetrosis
 Bleeding Disorders
Primary hemostasis Secondary hemostasis
(Platelet and vessel) (Coagulation factor)

Signs Petechiae, Large ecchymosis,

Purpura, Hematoma
Small ecchymosis

Location Skin, Muscle,

Mucous membrane Intra-articular,
Deep connective tissue

Response when press on Stop bleeding Continue bleeding

Physical examination;
Sign of Bleeding
 Suspected diseases 1
Anemia & Bleeding disorder
Bone Marrow Failure
Autoantibodies
Anemia
Nutritional deficiency
Hereditary Excessive destruction of RBCs
Bleeding disorder
Platelet disorder (Thrombocytopenia & Platelet dysfunction)
Vessel disorder
Coagulation factor disorder
Physical Examination
 Physical Examination

• Vital Signs
 BT 37 C
 Pulse 110/min
 RR 20/min
 BP 90/60 mmHg

Reference value : 6-12 yr (girl)

 BT = 37 C
 Pulse = 90-110/min
 RR = 14-22/min
 BP = 100-120/60-75 mmHg

Richard E. Behrman, Robert M. Kliegman, Hal B. Jenson. Nelson textbook of pediatrics. 16th edition. W.B.Saunders company. Pennsylvania. 2000
General Appearance :
Markedly pale, No jaundice,
Petechiae at trunk, arms and legs

HEENT : No cervical lymphadenopathy

Abdomen :
Liver 5 cm. below RCM,
Liver span 12 cm,
Spleen 2 cm. below LCM

Others : Within normal limit

Differential Diagnosis 2
Differential Diagnosis From PE
 Decreased Production of RBCs
• Bone Marrow Failure
o Congenital and acquired aplastic anemia
o Congenital and acquired pure red cell
anemia
o Infiltrative (Leukemia, lymphoma, Myelofibrosis)
o osteopetrosis

Lab investigation; CBC, Bone Marrow Examination

Differential Diagnosis From PE
 Excessive destruction of RBCs
• Hereditary
o Thalassemia, G6PD def, PK def, spherocytosis,
elliptocytosis, HbS, etc.

• Aquired
o Autoantibodies ( ex; SLE, AIHA, TTP )

age group common , Arthritis , Jaundice

Physical Examination : No Jaundice

Lab investigation ; CBC, Special staining, Coomb’s test

Differential Diagnosis From History
 Decreased Production of RBCs
• Nutritional deficiency (inadequate intake)
o Iron, B12, folate deficiency anemia

Lab investigation : CBC, Serum ferritin,

TIBC (Total iron binding capacity)
 Bleeding disorder

• Platelet disorder
(Thrombocytopenia & Platelet dysfunction)
• Vessel disorder
• Coagulation factor disorder

Physical Examination : Petechiae

Lab investigation ; CBC, Bleeding time

 Suspected diseases 2
Anemia & Bleeding disorder

Bone Marrow Failure

Autoantibodies
Anemia
Nutritional deficiency
Hereditary Excessive destruction of RBCs
Bleeding disorder
Platelet disorder (Thrombocytopenia & Platelet dysfunction)
Vessel disorder
 Bone Marrow Failure
• Congenital and acquired aplastic anemia
PE : Hepatosplenomegaly
• Congenital and acquired pure red cell anemia
Why bleeding ?

• Infiltrative (Leukemia, lymphoma, Myelofibrosis )

• Osteopetrosis (rare)
 Laboratory Orders

• CBC

• BM Examination

• Special staining
Laboratory Investigation
 Laboratory Investigation

1. CBC

3. Special Staining

5. Bone marrow examination

7. Lactate Dehydrogenase ( LDH )

CBC (complete blood count) : series of test of the
peripheral blood

1.Red blood cell count(RBC Count)

2.Hemoglobin(Hb)
3.Hematocrit(Hct)
4.Red blood cell indices
-mean corpuscular volume(MCV)
- mean corpuscular Hemoglobin(MCH)
- mean corpuscular Hemoglobin
concentration(MCHC)
-Red blood cell distribution width (RDW)
5.White blood cell count and differential
count(WBC Count)
-lymphocyte -monocytes
-eosinophils -basophils
6.Blood smear
7.Platelet count (Plt count)
 CBC Normal value case
Red blood cell count 6-18 years old -
Count of the number of 4.0-5.5x106/microL
circulating RBCs in 1
mm3 of peripheral
venous blood.

Hemoglobin 11.5-15.5 g% 7 g%
Measure of the total
amount of Hb in the
blood

Hematocrit 35-40% 21%

Indirect measurement of
red blood cell number
and volume.

Hb , Hct Anemia
Source :Mosby’s Manual of diagnosis & Laboratory test,United state of america : Mosby Elsevier,2006
 CBC Normal value case
Mean Corpuscular Volume(MCV) 77-95 fl 85 fl
Measure of the average volume, or
size, of a single RBC and is therefore
used in classifying anemias.
MCV = Hct(%)x10
RBC (million/mm3)

Mean Corpuscular Hemoglobin 25-33 pg 33.5 pg

(MCH)
Measure of the average amount of
hemoglobin within an RBC
MCH = Hb(g/dL)x10
RBC (million/mm3)

Mean Corpuscular Hemoglobin 31-37 g% 33.5 g%

Concentration (MCHC) Measure of
the average concentration or
percentage of hemoglobin within a
single RBC.
MCHC = Hb(g/dL)x10
hematocrit (%)

MCV ,MCH ,MCHC Normocytic,Normochromic

Source :Mosby’s Manual of diagnosis & Laboratory test,United state of america : Mosby Elsevier,2006
 CBC Normal value case

White blood cell count and Adult/child>2 years 3,000 /mm3

differential count measurement of 4,500-13,500 /mm3
the total and differential WBC count
is a part of all routine laboratory Absolute lymphocyte
diagnostic evaluation. = normal
-neutrophils
-lymphocytes 54-62% 20%
-monocytes 25-35% 50%
-eosinophils 3-7% 8%
-basophils 1-3% 2%
-myeloblast 0-0.75% -
0 20%

Blood smear examination of the -RBC : normochromic normocytic

peripheral blood smear can provide a RBC
significant amount of information -WBC : N 20% L 40% M 8% E
concerning drugs and diseases that 2% Myeloblast 20%
affect the RBCs and the WBCs. promyeloblast 10%
-platelet : 5-6 /oil field

WBC Leukocytopenia
Blood smear Myeloblast,Promyelocyte
Source :Mosby’s Manual of diagnosis & Laboratory test,United state of america : Mosby Elsevier,2006
 CBC Normal value case
Platelet count an actual 150,000-400,000 /mm3 65,000 /mm3
count of the number of
platelet per cubic milliliter of
the blood.

Mean platelet volume (MPV) 7.4-10.4 /fL -

this test is helpful in the
evaluation of platelet disorder,
especially thrombocytopenia.

Platelet Thrombocytopenia

Source :Mosby’s Manual of diagnosis & Laboratory test,United state of america : Mosby Elsevier,2006
Hb , Hct Anemia
WBC Leukocytopenia
Platelet Thrombocytopenia

Pancytopenia with
Myeloblast,Promyelocyte

Bone Marrow Examination

 Special staining

•Reticulocyte Count

•Denatured hemoglobin
- Inclusion body
- Heinz body
 Reticulocyte Count

Definition
A blood test performed to assess the body's
production of immature red blood cells
(reticulocytes).

Source :Mosby’s Manual of diagnosis & Laboratory test,United state of america : Mosby Elsevier,2006
 Purpose
- Diagnosis
Provides information about the rate at which the
bone marrow is producing red cells .

- Monitoring
Use to monitor the response of bone marrow
response to treatment for anemia.

Source :Mosby’s Manual of diagnosis & Laboratory test,United state of america : Mosby Elsevier,2006
reticulocytes are characterized by a network of filaments & granules.
 Interpretation
Normal :0.5-2.5%. (reported as a percentage of the total red cells.)
In this case : Reticulocyte 0.3%

Abnormal :
Higher-than-normal percentage
- Bleeding,Erythroblastosis fetalis,Hemolytic anemia,
Kidney disease with increased erythopoietin production

Lower-than-normal percentage

- Bone marrow failure,Cirrhosis ,Folate deficientcy ,iron deficiency,

Vitamin B-12 deficiency, Radiation therapy, Kidney disease with

decreased erythropoietin production

Source :Mosby’s Manual of diagnosis & Laboratory test,United state of america : Mosby Elsevier,2006
 Special staining

•Reticulocyte Count

•Denatured hemoglobin
- Inclusion body
- Heinz body
 Inclusion bodies (Hb H Inclusions )

Definition : Oxidised Hb H,precipitated within red blood cells

Morphology : greenish-blue inclusion bodies appear in many
erythrocytes.

Associated disorder: Hb H disease

 Heinz body
• Definition : unstable hemoglobin which is denatured &
precipitated within red blood cells

• Morphology : 1 round body attatching to cell membrane,

refractile inclusions (not visible on a Wright stain film)

• Associated disorder:
- G6PD (Glucose - 6 - phosphatase Dehydrogenase)
- α-thalasemia
- Chronic liver disease

http://www.vet.uga.edu/vpp/clerk/Tarigo/NMBHzBad.jpg
 In this case
Denatured hemoglobin
- Inclusion bodies negative
- Heinz body negative

Exclude Associated disorder:

- G6PD (Glucose - 6 - Phosphatase Dehydrogenase)
- α-thalasemia
- Chronic liver disease
- Hb H disease
 Reticulocyte Production Index (RPI)

= reticulocyte(%) x Hct(%)
45
maturation time

0.3 x 21
= 45 x 2.5

= 0.056

Fauci,Braunwalk,Kasper,Hauser,Longo,Jameson
et al. Harrison’s principles of internal’s medicine.
17th ed. USA:McGraw-Hill Companies,Inc; 2008
Anemia & Bleeding disorder
Bone Marrow Failure
» Infiltrative (Leukemia, lymphoma, Myelofibrosis)
» aplastic anemia

Autoantibodies
Abnormal RBC morphology
Anemia
Nutritional (Iron)deficiency
Defect only erythroid series
Microcytic hypochromic RBC
Hereditary Excessive destruction of RBCs
Defect only erythroid series
Bleeding disorder
Platelet disorder (Thrombocytopenia & Platelet dysfunction)
Vessel disorder
Hb , Hct Anemia
WBC Leukocytopenia
Platelet Thrombocytopenia

Pancytopenia with
Myeloblast,Promyelocyte

Bone Marrow Examination

Bone Marrow Examination
Indications
• Virtually pancytopenia in peripheral blood cell

• Found blast cell in peripheral blood

Source: Bernadette F. Rodak, Hematology Clinical Principles and Applications,

Third edition, Elsevier,USA, 2007
 Bone Marrow examination

A. Aspirate
1. M/E ratio(ratio of myeloid to erythroid precursors)
2. Cell morphology
3. Iron stain

B. Biopsy
1. Cellularity
2. Morphology
3. Iron stain
4. M/E ratio

Souce : Anthony S. Fauci, Eugene Braunwald, Dennis L. Kasper, Stephen L. Hauser, Dan L. Longo, J.
Larry Jameson, and Joseph Loscalzo, Eds : Harrison's Principles ofInternal Medicine, 17th Edition :
http://www.accessmedicine.com
Advantage of bone marrow aspiration & biopsy

aspiration biopsy
-appropriate in some clinical settings the -useful for determing cellularity and
diagnostic question is very targeted such as anatomic relationship of cell to fat and
connective tissue stroma
1. diagnosis of childhood immune
thrombocytopenia purpura -diagnosing infiltrative diseases

2. routine surveillance follow-up of -diagnosing and following the course of

leukemia patients.
disorders such as
1. reticulin fibrosis
2. hairy cell leukemia
3. chronic myeloproliferative disorders
Sites of bone marrow aspiration

Site Age when practical

Tibia Birth to 12 mo
Femur Birth to 12 mo
Anterior iliac crest Any age
Posterior iliac crest Any age
Vertibral spinous process 2 yr and olde

Source:Robert I,Handi, Samuel E. lux, Thomas P. Stossel,Blood principles and

practice of hematology, Philadephia:Lippincoh Williams K Wilkins,2003
Sites of bone marrow examination

Strenu Posterior iliac

crest
m
Anterior
iliac crest

Tibia

The patient is prone or in the left or right lateral

decubitus position.
 Bone marrow examination
• Cellularity
normal cellurality
hypercellularity
hypocellularity
• M:E ratio ( myeloid : erythroid )
normal ( 3:1 – 4:1 )
• Erythroid maturation
• Myeloid maturation
• Blasts
• Other

Source:Robert I,Handi, Samuel E. lux, Thomas P. Stossel,Blood: principles

and practice of hematology, Philadephia:Lippincoh Williams K Wilkins,2003
 Normal bone marrow

normal adult marrow (H&E stain)

- showing a mix of fat cells (clear areas) & hematopoietic cells.
- normal marrow cellularity is 35–40%.
- M/E Ratio = 3 : 1
 Bone marrow Examination

In this case

• Bone marrow aspiration

– Hypercellurality
– increased number of myeloid series
– myeloblast 85% with Auer rods
In this case

= Auer
rod
= Myeloid
blast
Pertinent subjective data
– Bone Marrow Failure
•Leukemia
•Aplastic anemia
Not found blast cell peripheral
blood
Low hematopoietic cell in BM
• lymphoma
Not found increased lymphoid blast cell
in BM examination
•myelofibrosis
Not found increased collagen and
fibrosis in BM examination
 Leukemi
a
Acute Chronic
Leukemi Leukemi
a
Blasts predominant Morea
mature cells
Children or elderly Midlife age range
Short and drastic course Longer, less devastating course

ALL AML CLL CML

Lymphoblasts
(pre – B or pre – T) - Myeloblasts -Lymphocytes Myeloid stem cells
- Auer rod -Non -Ab- producing “Blast crisis”
->20% of blast B cells
cell(WHO criteria)
-promyelocyte

Hagop M. Kantarjian, Robert A. Wolff, Charles A. Koller,MD Anderson Manual of Medical

• Bone marrow biopsy
– Acute myeloblastic leukemia
(Acute non-lymphoblastic leukemia)
 Lactate Dehydrogenase ( LDH )
- LDH is found in the cell of many body tissues, especially heart, liver,
RBC, kidneys, skeletal muscle, brain and lung

- LDH has 5 subtype - LDH1 mainly from heart

- LDH2 mainly from reticuloendothelial sys.
- LDH3 come form lungs and the other tissues
- LDH4 form kidney placenta and pancreas
- LDH5 form liver and striated muscle

- This enzyme used to supportive diagnosis of injury or disease involving the

heart, liver, red blood cell, kidneys, skeletal muscle, brain, and lung

- In this case : serum LDH 2480 U/L

(Normal 150-500 U/L)

Source :Mosby’s Manual of diagnosis & Laboratory test, United state of america : Mosby Elsevier,2006
CBC
Hb , Hct Anemia
Conclusion
WBC Leukocytopenia
Platelet Thrombocytopenia
Myeloblast

Bone marrow aspiration

Hypercellurality
increased number of myeloid series
myeloblast 85% Acute myeloblastic leukemia
Bone marrow biopsy (AML)
Acute myeloblastic leukemia
(Acute non-lymphoblastic leukemia)
with Auer rods

Lactase Dehydrogenase ( LDH )

serum LDH 2480 U/L
Basic Science
Haematopoiesis
Robbins and Cotran. Pathologic basis of disease. 7th edition.Elsevier Saunders.2005
http://content.answers.com/main/content/wp/en-commons/thumb/0/0d/400px-Hematopoiesis_(human)_diagram.png
Granulocytic series
 Leukemia

General concepts

1. Malignancies of hematopoietic cell origin.

2. Infiltrated with leukemic cells in

- BM failure of normal haematopoiesis

- Other organs: Liver, Spleen, Lymph nodes

Arthur S. Schneider, Philip A. Szanto. Pathology. 3rd edition. Lippincott Williams& Wilkins. 2006.
 Classification of Leukemia
Classification : according to cell lineage

Cell type Acute Chronic

Myelogenous leukemia Acute myelogenous leukemia Chronic myelogenous

( "nonlymphocytic") (AML) leukemia (CML)

Lymphocytic leukemia Acute lymphoblastic leukemia Chronic lymphocytic

( "lymphoblastic") (ALL) leukemia (CLL)
 Characteristic
AML: Accumulation of immature myeloid forms in the BM
and the suppression of normal hematopoiesis.

ALL: Predominance of lymphoblasts (pre-B and pre-T cell)

in the blood circulation and BM.

CML: Increased production of terminally differentiated myeloid cells

CLL: Proliferation of lympoid stem cell that is capable of giving rise

to mature cells (almost always B-cell) but less capable of

differentiating into plasma cell
 Incident of Leukemia
• The most common childhood cancers, account for one third of pediatric malignancies.

ALL AML CML CLL

Incident <10 yrs. Peak incident in 25-60 yrs. >60 yrs.

adult between15-39 yrs.

~75% of all cases ~20% of leukemias, with 5% rarely affects

in children and an incidence that is children.
has a peak stable from birth through
incidence at age age 10
4 yr.

Richard E. Behrman, Robert M. Kliegman, Hal B. Jenson. Nelson textbook of pediatrics. 16th edition. W.B.Saunders company. Pennsylvania. 2000
 ALL AML

http://www.accessmedicine.com/loadBinary.aspx?name=licha&filename=licha_VII.G.011.jpg
 CML CLL

http://medicineworld.org/images/blogs/12-2007/chronic-lymphoid-leukemia.jpg
Acute Myeloid Leukemia
(AML)
Acute Myeloid Leukemia (AML)
Classification
World Health Organization Classificationa 

I. AML with recurrent genetic abnormalities

AML with t(8;21)(q22;q22);RUNX1/RUNX1T1b
AML with abnormal bone marrow eosinophils [inv(16)(p13q22) or t(16;16)(p13;q22);CBFB/MYH11]b
Acute promyelocytic leukemia [AML with t(15;17)(q22;q12) (PML/RAR    ) and variants]b
AML with 11q23 (MLL) abnormalities

II. AML with multilineage dysplasia

Following a myelodysplastic syndrome or myelodysplastic syndrome/myeloproliferative disorder
Without antecedent myelodysplastic syndrome

III. AML and myelodysplastic syndromes, therapy-related

Alkylating agent–related
Topoisomerase type II inhibitor–related
Other types

IV. AML not otherwise categorized

AML minimally differentiated
AML without maturation
AML with maturation
Acute myelomonocytic leukemia
Acute monoblastic and monocytic leukemia
Acute erythroid leukemia
Acute megakaryoblastic leukemia
Acute basophilic leukemia
Acute panmyelosis with myelofibrosis
Myeloid sarcoma

French-American-British (FAB) Classificationc  Incidence 

M0: Minimally differentiated leukemia 5%

M1: Myeloblastic leukemia without maturation 20%

M2: Myeloblastic leukemia with maturation 30%

M3: Hypergranular promyelocytic leukemia 10%

M4: Myelomonocytic leukemia 20%

M4Eo: Variant: Increase in abnormal marrow eosinophils  

M5: Monocytic leukemia 10%

M6: Erythroleukemia (DiGuglielmo's disease) 4%

M7: Megakaryoblastic leukemia 1%

Fauci,Braunwalk,Kasper,Hauser,Longo,Jameson et al. Harrison’s principles of internal’s medicine. 17 ed. USA:McGraw-Hill Companies,Inc; 2008
th
 World Health Organization Classification
I. AML with recurrent genetic abnormalities
AML with t(8;21)(q22;q22);RUNX1/RUNX1T1b
AML with abnormal bone marrow eosinophils [inv(16)(p13q22) or t(16;16)
(p13;q22);CBFB/MYH11]b
Acute promyelocytic leukemia [AML with t(15;17)(q22;q12) (PML/RAR    ) and variants]b
AML with 11q23 (MLL) abnormalities

II. AML with multilineage dysplasia

Following a myelodysplastic syndrome or myelodysplastic syndrome/myeloproliferative
disorder
Without antecedent myelodysplastic syndrome

III. AML and myelodysplastic syndromes, therapy-related

Alkylating agent–related
Topoisomerase type II inhibitor–related
Other types

IV. AML not otherwise categorized

AML minimally differentiated
AML without maturation
AML with maturation
Acute myelomonocytic leukemia
Acute monoblastic and monocytic leukemia
Acute erythroid leukemia
Acute megakaryoblastic leukemia
Acute basophilic leukemia
Acute panmyelosis with myelofibrosis
Myeloid sarcoma
Conditions Predisposing to Development of AML
Environmental Factors Inherited Conditions
Radiation Sibling with AML
Benzene Amegakaryocytic thrombocytopenia, congenital
Alkylating agents and other cytotoxic drugs Ataxia-pancytopenia
Tobacco smoke Bloom syndrome
Congenital agranulocytosis (Kostmann syndrome)
Acquired Diseases Diamond-Blackfan syndrome
Clonal myeloid diseases Down syndrome
Chronic myelogenous leukemia Dubowitz syndrome
Idiopathic myelofibrosis Dyskeratosis congenita
Primary thrombocythemia Pure (nonsyndromic) familial AML
Polycythemia vera Familial platelet disorder
Clonal cytopenias Fanconi anemia
Paroxysmal nocturnal hemoglobinuria Naxos syndrome
Other hematopoietic disorders Neurofibromatosis 1
Aplastic anemia Noonan syndrome
Eosinophilic fasciitis Poland syndrome
Myeloma Rothmund-Thomson syndrome
Seckel syndrome
Shwachman syndrome
Werner syndrome (progeria)
Wolf-Hirschhorn syndrome
WT syndrome

http://www.accessmedicine.com/content.aspx?aID=2148252
 Molecular Pathogenesis
AMLs are associated with acquired
genetic alterations

Translocation Point mutation

t(8;21) & inv(16) t(15;17) Point mutation of FLT3

(tyrosine kinase) that result in
its constitutive activation
Affected CBF1α/CBF1β RARα fuse to PML protein

block terminal differentiation RARα,normally activates Promote cellular proliferation

transcription, is converted and survival
(but not sufficient to cause
to a repressor
leukemia)

Turn off genes required for

complete myeloid differentiation

AML

Robbins and Cotran. Pathologic basis of disease. 7th edition.Elsevier Saunders.2005

 Hypothesis: Case3
genetic alterations

Serum LDH
AML

Proliferation of neoplastic cell in BM Hypercellularity wt myeoblast

85% wt Auer rods
suppress normal hematopoietic stem cells
Found in peripheral blood
Peripheral blood:
Erythropenia Hct , Hb , Reticulocyte count Pale, Fatique

Thrombocytopenia Platelet Petechiae

Neutropenia Neutrophil Risk for opportunistic infection

compensate

Extramedullary hematopoiesis Hepatosplenomegaly

 AML treatment

• Immediate treatment at diagnosis

• Induction of remission

• Continuation or post-remission therapy

1) Immediate treatment at diagnosis
Bleeding
• Transfusion therapy: RBC Platelet

Fever and Infectious

• Antibiotic

Tumor Lysis Syndrome

• Fluid
• Sodium bicarbonate >>> Increase pH
• Allopurinol >>> Decrease Uric acid

Leukostasis = WBC > 200,000/cu.mm. >>> Blast cell aggregation

• Hydroxyurea
• Leukapheresis
• Exchange transfusion
2) Induction of remission
• to stop the growth of cancer cells
• to quickly induce complete remission (CR)

(4) Combination chemotherapy

(6) Bone marrow transplantation

> Esp. CA Drug resistance
> Relapse

(3) Radiation Therapy

> With or after chemotherapy
> Found Leukemic cells in CNS or CSF
 Mechanism of action
Doxorubicin
•Inhibition of DNA and RNA
synthesis by intercalation
between DNA base pairs
•inhibition of topoisomerase II
•iron-doxorubicin complex can
bind DNA and cell membranes
and produce free radicals that
immediately cleave the DNA
and cell membranes
Idarubicin Etoposide
• inhibition of DNA and • delay transit of cells
through the S phase and
RNA synthesis by arrest cells in late S or
early G2 phase
intercalation between
DNA base pairs • inhibit mitochondrial
transport at the NADH
dehydrogenase level
• inhibit uptake of
nucleosides into HeLa
cells
• topoisomerase II inhibitor
 ADRs

• Myelosuppression (Anemia, Leukopenia, Thrombocytopenia)

• GI disturbances, N/V, Alopecia

• Cardio toxicity
(Tachycardia, arrhythmias, dyspnea, Hypotension, CHF)

• Cerebella toxicity
3) Continuation / post-remission therapy

• to kill any remaining leukemia cells that may

not be active but could begin to regrow and
cause a relapse.

• to prolong the duration of the initial remission

3) Continuation / post-remission therapy
(1) Combination chemotherapy
• Maintenance therapy
Low Dose + Long time
• Consolidation therapy
In Dose Similar to given initially + Short time
• Intensification
High Dose/ Change CA Drug

(2) Bone marrow transplantation

Side effects of conditioning therapy
• Nausea and vomiting
• Diarrhea
• Mucositis
• Hair loss
• Loss of blood cell formation
• Pneumonitis (pneumonia)
• Occlusion (blockage) of veins in liver
• Congestive heart failure
• Premature menopause*
• Infertility*
• Growth retardation*
• Cataracts*
* These effects are more likely to occur if total body irradiation
is required for conditioning.
 Psycho-Social

Psycho Counseling
- Anxiety - ให้กำำลังใจผู้ป่วย
- Depression - ให้ผู้ป่วยคิดในแง่บวก
- Loss of self-confidence - ให้ผู้ป่วยดูแลตัวเอง
- สร้ำงควำมมั่นใจให้กบั ผู้ป่วย

Social Counseling
- Isolation - ครอบครัวและคนใกล้ชิดเข้ำใจ
- Loss of self-confidence และให้กำำลังใจผู้ป่วย
- หำกผู้ปว่ ยมีปัญหำด้ำนควำม
สวยงำมและบุคลิกภำพ ให้ปรึกษำ
ผู้เชี่ยวชำญด้ำนควำมงำม
 References
• Richard E. Behrman, Robert M. Kliegman, Hal B. Jenson. Nelson textbook of
pediatrics. 16th edition. W.B.Saunders company. Pennsylvania. 2000
• Fauci,Braunwalk,Kasper,Hauser,Longo,Jameson et al. Harrison’s principles of
internal’s medicine. 17th ed. USA:McGraw-Hill Companies,Inc; 2008
• Robbins and Cotran. Pathologic basis of disease. 7th edition.Elsevier
Saunders.2005
• Mosby’s Manual of diagnosis & Laboratory test,United state of america : Mosby
Elsevier,2006
• Hagop M. Kantarjian, Robert A. Wolff, Charles A. Koller,MD Anderson Manual of
Medical Oncology
• Robert I,Handi, Samuel E. lux, Thomas P. Stossel,Blood principles and practice
of hematology, Philadephia:Lippincoh Williams K Wilkins,2003
• http://www.vet.uga.edu/vpp/clerk/Tarigo/NMBHzBad.jpg
• http://www.medindia.net/animation/bone-marrow-transplantation.asp
• http://www.leukemia-lymphoma.org/attachments/National/br_1203086953.pdf
• http://www.med.cmu.ac.th/dept/pediatrics/04-divisions_home_thai/08-hema-
onco-home/Panja-book/chapter5.htm
• http://www.cancer.gov/cancertopics/pdq/treatment/childAML
Th ank You
&