A 6.

5 YEAR OLD GIRL WITH

HYPERLEUKOCYTOSIS, FEBRILE
NEUTROPENIA, ACUTE
LYMPHOBLASTIC LEUKEMIA, AND
WELL NOURISHED

English case report

Ahimsa Yoga Anindita

1

Supervisor:
dr. Muhammad Riza, Sp. A(K), M.Kes.
dr. Septin Widiretnani, Sp.A, M.Kes.

INTRODUCTION
Acute lymphoblastic leukemia (ALL)

the most common leukemia type in children under

14 y.o
80% of acute leukemia in children
2

ACUTE LYMPHOBLASTIC LEUKEMIA

Malignancy in bone marrow due to progressive

infiltration of immature lymphoid cell
Late diagnosis and inappropriate medication will
cause fatal morbidity and mortality

PATIENT IDENTITY
Name
:A
Age
: 6 years 6 months
BW/BH
: 23 kgs / 123 cms
Sex
: female
Address
: Sukoharjo
Day of admission
: 30th July 2016
MR
: 01347770

PARENTS IDENTITY
FATHER

Name

: Mr. S

Age : 40 y.o
Education : Senior HS
Job : Farmer
Race: Javanese
Religion : Moslem

MOTHER

Name
: Mrs. S
Age
: 35 y.o
Education : Senior HS
Job
: Housewife
Race
: Javanese
Religion : Moslem
5

CHIEF COMPLAINT
PALE

(PATIENT WAS REFERRED FROM

PEDIATRICIAN OF OTHER HOSPITAL)

SUBJECTIVE DATA (HISTORY)

A week before admission, patient easily got sick,
weakness and became pale recurrently

There was a fever together with those complaints

Then she was hospitalized for about a week and

she got 3 packs of platelet concentrate due to
thrombocytopenia

The previous doctor asked for the peripheral

blood smear

Normochromic/normocytic anemia,
thrombocytopenia, and absolute lymphocytosis
suspected for a hematologic malignancy

Referred to Moewardi Hospital for confirming

the diagnosis

In Emergency Department of
Moewardi Hospital

Fully alert, pale, and weak

No spontaneous bleeding
No fever

History of past illness

No previous serious illness
Hospitalized in a private hospital

History of family illness

No history of malignancy

Livelihood environment
Lives in an area near active farm
Exposed by insecticide or pesticide usage

10

History of labour and pregnancy

Her mother was 28 y.o when she got pregnant of her
Spontaneous birth delivery, assisted by doctor in
local hospital

Nutritional history
She ate regular family menu and adult portion with
various dishes and vegetables
Adequate quality and quantity of nutrition

Development history
There was no delay in development status

11

Immunization
Complete according to Indonesia
Ministry of Health programme

Socioeconomic status
Middle income family

12

PEDIGREE

13

NUTRITIONAL STATUS

; p50 < < p75

; p 75 < < p90

; p25 < < p50

Conclusion : normal weight, normal height, and well

nourished (CDC 2000)

14

PHYSICAL EXAMINATION
General appearance : looked weak, fully alert, pale,
wellnourished
Heart rate
: 108 bpm, regularly, adequate filling
Respiratory rate : 22 breaths per minute , regularly
Temperature
: 36.6 0C
BW/BH
: 23 kgs / 123 cms

15

GENERAL STATUS

Head : mesocephal, HC = 48 cm (-2 SD < HC < 0 SD),

dismorfic face (-), black hair, old man face (-)

Eye

Ear

Nose

Mouth : stomatitis (-), gum bleeding (-), tounge bleeding (-)

Throat : hyperemic pharynx or tonsil (-), tonsil T1-T1

Neck

: pale conjuctiva (+/+), isocoric pupil, 2 mm/2 mm,

light reflex (+/+)
: discharge (-/-), pain (-/-)
: nasal flaring (-), epistaxis (-)

: multiple lymphadenopathy
16

 Chest wall : retracted (-), symmetric, no petechiae

Cardiac

Inspection : invisible apex beat

Palpation : palpable apex beat in ICS 4 at the left
midclavicle line
Percussion : no enlargement of heart border
Auscultation : normal heart sound, no murmur

17

Lung
Inspection : symmetric chest movement in breath
Palpation : tactile fremitus was equal
Percussion : sonor / sonor
Ausculatation : vesicular sound (+/+), no additional
sounds

Abdominal
Inspection : abdominal wall was in line with chest wall
Auscultation : normal peristaltic sound
Percussion : tympanic
Palpation : liver enlargement 3 cms below the right costal
18
margin, no spleen enlargement

Genitals : normal

Extremities : dorsal artery of foot (+) good pulse,

capillary refill time < 2, no petechiae

19

LABORATORY 30TH JULY 2016

Hemoglobin : 7.3 g/dl
Hematocrit : 22%
Leukocyte
: 24 thousand/ul
Platelet : 15 thousand/ul
Erythrocyte : 2.98 million/ul
MCV : 95.2 /um
MCH : 32.7 pg
MCHC
: 34.5 g/dl
Eosinophils : 0.00%
Basophils
: 0.00%
Neutrophils : 10.00%
Lymphocytes
: 33.00%
Monocytes
: 4.00%
ANC : 2400 /mm3

20

LIST OF PROBLEMS
A 6 years
6 months
y.o girl

Pale
Platelet transfusions history
Pale conjunctiva
Liver enlargement
Multiple cervical lymphadenopathy
Normocytic/normochromic anemia

21

LIST OF PROBLEMS
A 6 years
6 months
y.o boy

Thrombocytopenia
Leukocytosis
Suspected for hematologic
malignancy
Lives in active farm with
pesticide or insecticide

22

DIFFERENTIAL DIAGNOSIS
1.
2.

Acute lymphoblastic leukemia dd Acute

myeloblastic leukemia
Normal weight, normal height, wellnourished

23

WORKING DIAGNOSIS
1.
2.

Acute lymphoblastic leukemia

Normal weight, normal height, wellnourished

24

THERAPY

Hospitalized in pediatric hematology-oncolocy ward

Regular dishes diet 1500 Kcal/day
Infusion of D1/4NS 16 drops/min
Paracetamol (10 mg/kgBW/time) : 250 mg (if
necessary), temperature > 37.5C

25

PLAN

Peripheral blood smear examination

Thorax radiological examination

26

PATIENT MONITORING

27

DATE

DAY 2-3 (August 1-2 2016)

Looked pale and weak, no spontaneous bleeding

Sustained well

HR : 88-104 x/, RR : 24 x/, S: 36.6-37.1C,

Pale conjuctiva
enlargement (+)

(+/+),

multiple

cervical

lymphadenopathy

(+),

liver

Urinalysis and stool examination results were normal

Laboratory

Peripheral blood smear : bicytopenia with leukocytosis, lymphoblast (+),

suspected for acute hematologic malignancy, suggested for BMP examination
Thorax radiological examination : normal, no mediastinal mass

ALL dd AML, wellnourished

Others were still same
BMP

28

PERIPHERAL BLOOD SMEAR

29

THORAX X-RAY

30

DATE

DAY 4 (August 3 2016)

New petechiae on anterior chest wall, epistaxis

Sustained stable
HR : 106 x/, RR : 24 x/, S: 36.6-37.4C,

Pale conjunctiva (+/+), multiple cervical lymphadenopathy (+), liver

enlargement (+), epistaxis (+)
Petechiae (+) on anterior chest wall

Laboratory

Hyperleukocytosis, thrombocytopenia, normochromic/normocytic anemia

ALL dd AML, well nourished

Hyperleukocytosis management

4 packs of platelet concentrates

BMP

31

Therapy

Hyperleukocytosis management :
- Hydration by D1/4S infusion112 ml/hour
- Allopurinol (10 mg/kgBW/day) = 75 mg/8 hours orally
- Diuresis measurement, when the diuresis < 3
ml/kgBW/hour : Furosemide (1 mg/kgBW/day) = 25 mg IV
- Urine alkalinization (pH of urine < 7.5 : bicarbonate
tablet 35 meq
- Routine check for blood and electrolyte every 24 hours
- Tumor lysis syndrome monitoring

32

LABORATORY AUGUST 3, 2016

Hemoglobin : 6.5 g/dl
Hematocrit : 19%
Leukocyte
: 69.4 thousand/ul
Platelet : 9 thousand/ul
Erythrocyte : 2.54 million/ul
MCV : 86.1 /um
MCH : 30.4 pg
MCHC
: 33.4 g/dl
Eosinophils : 0.00%
Basophils
: 0.00%
Neutrophils : 10.00%
Lymphocytes
: 33.00%
Monocytes
: 4.00%
Reticulocyte : 0.35%
ANC : 6940 /mm3

33

DATE

DAY 5 (August 4 2016)

No spontaneous bleeding
Sustained stable

Laboratory

HR : 100 x/, RR : 24 x/, S: 36.5-37.1C, Diuresis : 3.69 cc/kgBW/hour

Pale conjuctiva
enlargement (+)

(+/+),

multiple

cervical

lymphadenopathy

(+),

liver

Leukocytosis, thrombocytopenia, normochromic/normocytic anemia

ALL dd AML, well nourished

Hyperleukocytosis management was stopped

1 pack of PRC transfusion for targetting Hb to 8 g/dl

BMP

34

LABORATORY AUGUST 4 2016

Hemoglobin : 5.1 g/dl
Hematocrit : 14%
Leukocyte
: 39.9 thousand/ul
Platelet : 22 thousand/ul
Erythrocyte : 2.12 million/ul
MCV : 88 /um
MCH : 28 pg
MCHC
: 35.4 g/dl
Neutrophils : 8.00%
Lymphocytes
: 83.80%
PT : 16.3 seconds
APTT : 27.5 seeconds
Na : 134 mmol/l
Kalium : 5.0 mmol/l
Calsium : 1.19 mmol/l
Chloride : 104 mmol/l
Ureum
: 16 mg/dl
Creatinine : 0.3 mg/dl
Uric acid : 3.6 mg/dl
ANC : 3192 /mm3

35

DATE

DAY 6 (August 5 2016)

Looked weak and pale

Sustained well

Laboratory

HR : 98 x/, RR : 24 x/, S: 36.5-37.1C

Pale conjuctiva
enlargement (+)

(+/+),

multiple

cervical

lymphadenopathy

(+),

liver

Leukocytosis, thrombocytopenia, normochromic/normocytic anemia

ALL dd AML, well nourished

1 pack of PRC transfusion for targetting Hb to 10 g/dl
BMP

36

LABORATORY AUGUST 5 2016

Hemoglobin
: 7.3 g/dl
Hematocrit
: 21%
Leukocyte
: 36.4 thousand/ul
Platelet
: 22 thousand/ul
Erythrocyte
: 3.01 million/ul
MCV
: 89.7 /um
MCH
: 32.2 pg
MCHC
: 34.9 g/dl
Neutrophils
: 7.40%
Lymphocytes
: 84.70%
ANC
: 2693.6 /mm3

37

DATE

DAY 7-8 (August 6-7 2016)

Looked weak and pale, new spontaneous bleeding (2x

bleeding from nose)
Sustained stable

Laboratory

HR : 86-100 x/, RR : 18-24 x/, S: 36.5-37.3C

Pale conjuctiva (+/+), multiple
enlargement (+), epistaxis (+)
Leukocytosis,
neutropenia

thrombocytopenia,

cervical

lymphadenopathy

(+),

normochromic/normocytic

liver

anemia,

ALL dd AML, well nourished

Consulted to ENT Department -> no specific treatment for epistaxis

7 packs of platelet transfusion

BMP

38

LABORATORY AUGUST 6 2016

Hemoglobin
: 10.5 g/dl
Hematocrit
: 33%
Leukocyte
: 35.9 thousand/ul
Platelet
: 8 thousand/ul
Erythrocyte
: 4.11 million/ul
MCV
: 89.0 /um
MCH
: 28.6 pg
MCHC
: 33.3 g/dl
Neutrophils
: 3.10 %
Lymphocytes
: 83.70%
ANC
: 1112.9 /mm3

39

DATE

DAY 9-11 (August 8-10 2016)

No complaint, but looked weak, no spontaneous bleeding

Sustained stable

Laboratory

HR : 88-108 x/, RR : 22-24 x/, S: 36.5-37.0C

Pale conjuctiva
enlargement (+)

(+/+),

multiple

cervical

lymphadenopathy

(+),

liver

ALL L2 type (based on BMP on August 10 2016)

ALL L2 type High Risk (HR) (started from August 10 2016)

BMP (on August 8 2016)

40

DATE

DAY 12 (August 11 2016)

spontaneous bleeding (1x)

Sustained stable
HR : 88-104 x/, RR : 20-24 x/, S: 36.7-37.0C

Pale conjuctiva
enlargement (+)

(+/+),

multiple

cervical

lymphadenopathy

(+),

liver

gum bleeding (+), tounge bleeding (+)

Laboratory

Leukocytosis, thrombocytopenia, normochromic/normocytic anemia

ALL L2 type High Risk (HR)

7 packs of platelet transfusion

Motivation and education to parents related to the disease and therapy 41

Preparation for initial chemotherapy

LABORATORY AUGUST 11 2016

Hemoglobin
: 8.1 g/dl
Hematocrit
: 26%
Leukocyte
: 40.3 thousand/ul
Platelet
: 15 thousand/ul
Erythrocyte
: 3.32 million/ul
MCV
: 87.3 /um
MCH
: 28.4 pg
MCHC
: 34.5 g/dl
Neutrophils
: 4.00%
Lymphocytes
: 21.00%
ANC
: 1612 /mm3

42

DATE

DAY 13 (August 12 2016)

No complaint, no spontaneous
intrathecal procedure

bleeding,

fever

after

Sustained stable

HR : 94 x/,
procedure)

RR : 26 x/, S: 36.8-37.2C and 39.2C (after intrathecal

Pale conjuctiva
enlargement (+)

(+/+),

multiple

cervical

lymphadenopathy

(+),

liver

Leukocytosis, thrombocytopenia, anemia

Laboratory

(Hb 6.4 g/dl, Ht 22%, WBC 31.9 thousand/ul, Platelet 30 thousand/ul, RBC
2.79 million/ul)

ALL L2 type High Risk (HR) during chemotherapy in induction phase week 0
Methrotexate 12 mg intrathecally

Tappering up dexamethasone 6 mg/m2/day started from 1-1-0

2 packs of PRC transfusion for targetting Hb to 10 g/dl

43

Therapy

Planned for CSF analysis in Anatomycal Pathology

Department for blast cell presence in CSF
After evaluating patient with fever in hematologic
malignancy, it was suspected for febrile neutropenia
- Gentamycin (5 mg/kgBW/24 hours) = 100 mg/24 hours
intravenously (I)
- Cefotaxime (50 mg/kgBW/8 hours) = 1 g/8 hours
intravenously (I)
- Paracetamol (10 mg/kgBW/6 hours) = 250 mg/ 6 hours
intravenously or orally
- Planned for blood culture before antibiotic
administration

44

DATE

DAY 14-16 (August 13-15 2016)

Fever
Sustained stable

Laboratory

HR : 98-116 x/, RR : 22-26 x/, S: 37.8-38.4C

Pale conjuctiva (+/+), multiple cervical
enlargement (+), hyperemic pharynx (+)

lymphadenopathy

(+),

liver

Thrombocytopenia, neutropenia
No blast cell in CSF
ALL L2 type High Risk (HR) during chemotherapy in induction phase week 0

Acute pharyngitis
Febrile neutropenia
Tappering up dexamethasone 3-2-2 (August 15 2016)

Antibiotics administration was continued untill 5 days

Planned for throat swab culture (on August 13 2016)

45

LABORATORY AUGUST 13 2016

Hemoglobin : 12.7 g/dl
Hematocrit : 39%
Leukocyte
: 5.8 thousand/ul
Platelet : 33 thousand/ul
Erythrocyte : 4.80 million/ul
MCV : 81.7 /um
MCH : 28.5 pg
MCHC
: 33.4 g/dl
Eosinophils : 0.30%
Basophils
: 0.20%
Monocytes
: 7.50%
Neutrophils : 2.60%
Lymphocytes
: 89.40%
ANC : 150 /mm3

46

DATE

DAY 17-19 (August 16-18 2016)

New spontaneous bleeding on the skin

Sustained stable

HR : 94-118 x/, RR : 20-26 x/, S: 36.7-37.4C

Pale conjuctiva (+/+), multiple cervical lymphadenopathy (+),
enlargement (+), petechiae on the skin in upper and lower extremities

liver

Normocytic/normochromic anemia, thrombocytopenia, neutropenia

Laboratory

Blood culture : no growth (August 18 2016)

Throat culture : no growth (Auguat 16 2016)

ALL L2 type High Risk (HR) during chemotherapy in induction phase week 0
Neutropenia
8 packs of platelet transfusion

Cefixime (5 mg/kgBW/12 hours) = 100 mg/12 hours orally

Planned for chemotherapy in induction phase week 1

47

LABORATORY AUGUST 16 2016

Hemoglobin : 10.2 g/dl
Hematocrit : 31%
Leukocyte
: 1.8 thousand/ul
Platelet : 11 thousand/ul
Erythrocyte : 3.83 million/ul
MCV : 81.9 /um
MCH : 29.6 pg
MCHC
: 33.5 g/dl
Eosinophils : 1.10%
Basophils
: 0.50%
Monocytes
: 3.30%
Neutrophils : 10.50%
Lymphocytes
: 84.60%
ANC : 189/mm3

48

DATE

DAY 20 (August 19 2016)

No complaint
Sustained well

Laboratory

HR : 96 x/, RR : 22 x/, S: 36.5-37.3C

Pale conjuctiva (-/-), multiple cervical lymphadenopathy (+), liver enlargement
(+)
Normocytic/normochromic anemia, thrombocytopenia, neutropenia
ALL L2 type High Risk (HR) during chemotherapy in induction phase week 1
Neutropenia
Vincristine (1.5 mg/m2) = 1.3 mg intravenously

Dexamethasone had been in full dose (4-3-3) = 5 mg/day orally

Cefixime (5 mg/kgBW/12 hours) = 100 mg/12 hours orally
Planned for discharge

49

LABORATORY AUGUST 19 2016

Hemoglobin : 9.8 g/dl
Hematocrit : 30%
Leukocyte
: 1.9 thousand/ul
Platelet : 32 thousand/ul
Erythrocyte : 3.70 million/ul
MCV : 80.7 /um
MCH : 30.5 pg
MCHC
: 33.8 g/dl
Eosinophils : 0.40%
Basophils
: 0.20%
Monocytes
: 2.80%
Neutrophils : 14.10%
Lymphocytes
: 82.50%
ANC : 267.9/mm3

50

Therapy

Patient could be discharged

She received cefixime as oral antibiotic administration at
home
Then she was planned to come back for receiving
chemotherapy in induction phase week 2

51

CASE ANALYSIS

52

Based on this case :

Patient with pale
Normocytic/normochromic anemia
Leukocytosis

Peripheral blood smear before any transfusion

(is there any blast cell ?)
Confirm the diagnosis by BMP

53

IN THIS CASE, WHAT IS THE MAIN

CAUSE ?
No malignancy history in family
No history of X-Ray exposure
Her father works as a farmer, this condition
increases the risk factor of acute leukemia

But, there is a history for exposure to

organophosphates (OP), such as pesticide and
insecticide

54

ORGANOPHOSPHATES AGENTS

Exposure of this chemical agent can be as

ingestion, inhalation, or dermal contact
Biochemical process

Increased production of reactive oxygen species

(ROS)
ROS overproduction

Superoxide can lead to hematologic malignancy

due to DNA and protein damage

55

ACUTE LYMPHOBLASTIC LEUKEMIA

Abnormal proliferation from hematopoietic cell in

granulocyte series

Progressive immature lymphoid cells from bone

marrow and lymphoid organ supress the
production of platelet and RBC
infiltration

Other organs (liver, spleen, lymph nodes)

56

Progressive proliferation of lymphoid cells can

cause hyperleukocytosis

Plug in a any organ (leukostasis)

Inadequate
management

Brain : cephalgia, Eye : sudden blind, Respiratory

organ : dyspnea, Cardiac organ : sudden death
Monitoring for tumor lysis syndrome

57

FEBRILE NEUTROPENIA AFTER

CHEMOTHERAPY

Administration of the 1st chemotherapy agent

Supress the bone marrow function

Decreased production of certain cells, such as

neutrophil for the immune system

Patient is easly infected by pathogens

58

Episode of hyperleukocytosis makes the reason

why this patient was diagnosed to be high risk
High risk has worse prognosis than standard risk

59

60

Thank
you