precursor B CELL ACUTE LYMPHOBLASTIC LEUKEMIA

2. Case presentation
 Dr ASIF REHMAN
 PG TRAINEE MEDICAL
UNIT 2
 CIVIL HOSPITAL
LALRKNA

3.  18 Years old female
NOOR BANOO d/o
MASHOOQ, resident
of larkana, admitted
in medical unit 2
civil hospital larkana
on 28th February
2017 via emergency
with chief complain
of:

4. Chief complain
 Fever with headache for 4 months
 Shortness of breath for 15days.

5. HOPC
 According to my patient, She was in usual state of health 4
months back when she developed fever which was sudden
in onset, high grade , continued in nature, associated with
rigors & chills and with night sweats. it relieved temporarily
by taking panadol. Fever was associated with generalized
sever headache along with vomiting.
 During this illness, Patient has h/o loss of appetite and
Approximately 4 to 5 kilogram loss of her body weight.
 She also complained of bony pains that involved (
backbone, ribs and sternum) for last 1 to 2 months.

6. HOPC
Patient reported shortness of breath for15 days
which was gradual in onset and was progressive
that worsened with lying down & walking,
associated with chest pain.
There is no history of jaundice, rashes, burning
micturition, cough,PND, hematemesis and
hemoptysis OR joint pain.

7. PAST HISTORY
 No past medical history of TB,IHD & hepatitis or
hospitalization
No h/o allergies
Pt has h/o immunization.

8. DRUG HISTORY
 Tab panadol
syp lysovit
CAP risek 20 mg
There is history of transfusion of two pints of whole
blood 2 months back.

9. PERSONAL HISTORY
 She is unmarried
 Non smoker,
 Sleep pattern is disturbed
 h/o weight loss
 Decreased appetite
 Bladder And bowel habits are normal

10. FAMILY HISTORY
 Her father and mother are healthy and normal
 She has three sisters
 All are healthy and normal.

11. SOCIOECONOMIC HISTORY
 Patient belongs low socioeconomic status
 Lives in cemented house
 Father is the only earner
 Hygienic conditions are satisfactory.

12. CASE SUMMURY
 18 years old NOOR BANO admitted via ER with
complain of high grade, continued fever for 4 months,
associated with chills & rigors, headache and vomiting,
along with 4 to 5kg body weight loss.
 Patient also complain of progressive shortness of breath
for15 days, associated with chest pain.
 Patient has bony pains but no h/o jaundice, rashes, burning
micturation, cough, hematemesis , hemoptysis or joint
pains.
 There is history of transfusion of two pints of whole blood
2 months back.

13. DIFFERENTIAL
DIAGNOSIS

14. CLINICAL EXAMINATION

15. GENERAL PHYSCIAL
EXAMANITION
 A young age female of average height and built ,
sitting comfortably on bed , cannulated in right
arm , well oriented with time , place and person.

16. vitals
 BP: 110/70 mmhg
 Pulse: 108 beats/minute
 R/R: 22breaths / minute
 Tem: 102F

17. SUB VITALS
 Pallor- present JVP-not raised
 Jaundice-Absent THYROID-not
enlarged
 Cyanosis-absent LYMPH N- not
palpable
 Clubbing-absent BONY TENTERNESS-
PRESENT
 Edema-absent
 Koilonychias-absent
 Palmer Erythema-absent.

18. SYSTEMIC
EXAMINATION
 Central Nervous System
Higher psychiatric function : she is conscious, well oriented with time, place
and person, normal speech and intact recent and past memory
Examination of cranial nerves : all cranial nerves are intact.
Sensory system : normal
Motor functions
Bulk of muscles : normal
Tone of the muscles: increased
Power of the muscle: normal 5/5 in all limbs
Deep reflexes ( ankle , knee, biceps and triceps) : +2
Plantar reflex : up going bilaterally
signs of meningeal irritation: neck rigidity and kerning`s sign positive

19.  Respiratory System
 Inspection: not allowed with out clothes, apparently
shape of chest seems to be normal with reduced movements
on right side of chest
 Palpation
Trachea: Central.
Apex beat: In the left 5th intercostal space in midclavicular line, 8
cm from midsternal line, normal in character
Chest expansion: Reduced (1cm)
 Percussion: Area of liver dullness in 5th ICS in the right
midclavicular line
 Percussion note: stony dull on right side of chest from 7th
intercostal space to down ward posteriorly

20.  Auscultation :
breath sounds were diminished on right lower chest from 7th
intercostal space to downward posteriorly
Vocal resonance: reduced on right lower side of chest
posteriorly

21.  Gastrointestinal System
Abdominal examination was normal except pt had
palpable spleen ,5 to 6 cm from left costal margin in anterior
axillary line with regular surface ,soft to firm in consistency and
non tender
(Liver span 12cm).

22.  Cardiovascular System
 Pulse rate : 108beats/min, With regular rhythm and normal
volume pulse
 JVP not raised,
 Apex beat: In the left 5th intercostal space in midclavicular
line, 8 cm from midsternal line, normal in character
 Area of cardiac dullness: Normal.
 Auscultation: . 1st and 2nd heart sounds are audible
 Added sounds are not present.

23. Case Summary
 18 years old NOOR BANO admitted via ER with complain of high
grade, continued fever for 4 months, associated with chills & rigors,
headache and vomiting, along with 4 to 5kg body weight loss.
 Patient also complain of progressive shortness of breath for15 days,
associated with chest pain.
 Patient has bony pains but no h/o jaundice, rashes, burning micturition,
cough, hematemesis , hemoptysis or joint pains.
 There is history of transfusion of two pints of whole blood 2 months
back.
 Examination revealed anima and bony tenderness.
 Moderate splenomegaly,
 Increased muscle tone with up going planters & positive SOMI
 Right side of chest : Reduced chest expansion, stony dull percussion
note, reduced breath sounds & reduced VR.

24. INVESTIGATIONS

25. CBC

26. COMPLETE BLOOD COUNT
 Hemoglobin- 8g/dl
Haematocrit-25%
M.C.V-98 Fl
M.C.H-31 pg
M.C.H.C-31.7 g/d
Platelets- 200*10E/L
 W.B.S - 128*10E/L
Neutrophills-3.1 %
Lymphocytes -71.0%
Eosinophil's -.01 %
Monocytes- 25%
Basophils – 0.0 %

27. PERIPHERAL FILM
 Macrocytic ,normochromic red cells, platelets are normal in
film
 75% blast cells are seen.

28. X-RAY CHEST

30. Ultrasound REPORT

31. LFT , URINE DR
S.UREA CREATININE NORMAL

32. BlOOD CULTUR:

33. Pleural effusion DR

37. MRI-BRAIN

38. MRI BRAIN REPORT..

39. CERIBEROSPINAL FLUID DR

40. CSF ACID FAST BACILLI
SMEAR

41. LDH LEVEL
LDH level =538

42. BONE MARROW
BIOPSY

43. BONE MARROW
BIOPSY

44. BONE MARROW BIOPSY….
Conclusion….
 BONE MARROW ASPIRATION : Hypercellular
specimen shows diffuse infiltration with blast cells
which constitute around 82% of total nucleated,
nonerythroid cells population. These blast cells are
medium in size having high nuclear to cytoplasmic
ratio, agranular cytoplasmic, fine chromatin and
inconspious nucleoli
 Normally hematopoiesis is markedly suppressed
 BONE MARROW TREHINE :Good length of
specimen showing effected architecture with overall
cellularity of 90 -95%. There is diffuse infiltration with
blast cells

45. Conclusion….
 IMMUNOPHENOTYPE OF BLAST CELLS:
 CD34 : Diffuse positive
 TdT : Diffuse positive
 CD79: Diffuse positive.
 CD3: NEGATIVE
 MPO : NEGATIVE
 FINDINGS ARE CONSISTENT WITH PRECURSOR-
B CELLACUTE LYMPHOBLASTIC LEUKEMIA.

46. Conclusion…
 CYTOGENETICS REPORT :
 45XX,(9;22)(q34;q11.2),-20(15)
 15 cells were counted, all cells were positive for
Philadelphia chromosome.
 Case comment: all cells showed translocation between
chromosomes 9q34 and 22q11.2 and-20.

47. CYTOGENETIC
REPORT OF BONE
MARROW

48. BONE
MARROW
CHROMOSOM
E

49. DIAGNOSIS
PRECURSOR- B CELL
ACUTE
LYMPHOBLASTIC
LEUKEMIA
with
Philadelphia
chromosome
CNS INVOLVEMENT

54. The Acute Leukemias
 Acute lymphoblastic leukemia (ALL) is a malignant (clonal)
disease of the bone marrow in which early lymphoid
precursors proliferate and replace the normal
hematopoietic cells of the marrow.
 The acute leukemias were usually malignancies of blast
cells with few identifying characteristics
 acute lymphoid leukemias (ALLs) are pre- dominantly
cancers of children and young adults.
 All lymphoid cells are derived from a common
hematopoietic pro- genitor that gives rise to lymphoid,
myeloid, erythroid, monocyte, and megakaryocyte lineage.

55. STAGES of differentiation of B CELLS
AND THERE malignancies

57. CLASSIFICATION OF ACUTE LYPHOID
LEUKIMIA

60. PROGNOSIS
 Only 20-40% of adult with acute lymphoblast
leukemia are cured with poor risk criteria with current
treatment.
 Patients with ALL are divided in to GOOD RISK and
POOR RISK CRITERIA.

61.  Age younger than 30
years
 WBC Count less than
30,000/uL
 No adverse cytogenetics
 No CNS and testicular
disease
 Female patient
 LDH not high
 HYPERDIPLOIDY
 Rapid response to
induction therapy
 Age older than 60
years
 Precursors B-cell
with WBC
>100,000/uL
 Adverse
cytogenetics-
translocation t(9;22)
,t(4;11)
CNS or TESTICULAR
disease at
presentation
 Male patient
 High LDH level
 HYPODIPLOIDY
 No Remission in
GOOD RISK CRITERIA POOR RISK CRITERIA

64. Treatment
THERE ARE TWO COMPONENT OF
TREATMENT
SUPORTIVE TREATMENT
SPECIFIC TREATMENT

65. SUPORTIVE TREATMENT
 Blood transfusion for anemia, platelets
concentrates for thrombocytopenia and granulocytes
for neutrophils.
 Antibiotics needed for control of infection, C0-
TRIMOXALE as prophylaxis for pneumocystis carinii
 Allopurinol 10 mg/kg/day 3dd for 10 days) is given
along with induction therapy to guard against with
development of uric acid nephropathy
 Adequate fluids and nutrition support
 Analgesics prescribed as required .

66. Specific therapy
 Traditionally there are four components of ALL
treatment
 INDUCTION CHEMOTHERAPY
 CONSOLIDATION CHEMOTHERAPY
 MAINTENANCE CHEMOTHERAPY
 CNS PROPHYLAXIS
 ALL WITH CNS INVOLVEMENT
 ALL WITH PHILADILPHIA CHROMOSOMES.

70. Consolidation therapy (2-4
WEEKS)
 It is given after induction therapy it removes residual
or resistant leukemic cells
 regimens using a standard 4- to 5-drug induction
usually include consolidation therapy with CYTOSINE
ARABINOSIDE(Ara-C) in combination with an
anthracycline or epipodophyllotoxin.

71. Maintenance Therapy (2-
5YEARS )
 6-mercaptopurine (50mg/d oral)
 Methotrexate 20mg?m2/wk oral .i.v
 With reinforcement :
Vincristine 1.5mg/m2 (max 2mg) i/v every 4weeks
Prednisone 40mg/m2/day *7 days every4 week.

72. CNS Prophylaxis
 patients with acute lymphoblastic leukemia (ALL)
frequently have meningeal leukemia at the time of
relapse. A minority of patients have meningeal disease
at the time of initial diagnosis
 high-dose systemic chemotherapy reduces CNS relapse
 early intrathecal chemotherapy is to achieve the
lowest risk of CNS relapse

73. CNS relapse rates
 31% for group 1 (standard chemotherapy, no CNS
prophylaxis),
 18% for group 2 (high-dose systemic chemotherapy,
no CNS prophylaxis
 17% for group 3 (high-dose systemic chemotherapy,
intrathecal chemotherapy for high-risk subjects after
achieving remission),
 3% for group 4 hyperfractionated
cyclophosphamide, vincristine, doxorubicin, and
dexamethasone (hyper-CVAD).

74. Treatment of Ph
Chromosome–Positive ALL
 the tyrosine kinase inhibitor (inhibits the bcr-abl
fusion protein of Ph+ ALL) = imatinib
Newer tyrosine kinase inhibitors
Nilotinib and dasatinib
Ponatinib
a kinase inhibitor, was approved by the US
Food and Drug Administration (FDA) in
December 2012 for patients with Ph+ ALL
that is resistant or intolerant to prior
tyrosine kinase inhibitor therapy.

75. Transplantation
 Hematopoietic stem cell transplantation
(HSCT) seems to be a valuable option for ALL
carrying poor prognostic factors.