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Case presentation
 Dr ASIF REHMAN
 PG TRAINEE MEDICAL
UNIT 2
 CIVIL HOSPITAL
LALRKNA
 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:
Chief complain
 Fever with headache for 4 months
 Shortness of breath for 15days.
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.
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.
PAST HISTORY
 No past medical history of TB,IHD & hepatitis or
hospitalization
No h/o allergies
Pt has h/o immunization.
DRUG HISTORY
 Tab panadol
syp lysovit
CAP risek 20 mg
There is history of transfusion of two pints of whole
blood 2 months back.
PERSONAL HISTORY
 She is unmarried
 Non smoker,
 Sleep pattern is disturbed
 h/o weight loss
 Decreased appetite
 Bladder And bowel habits are normal
FAMILY HISTORY
 Her father and mother are healthy and normal
 She has three sisters
 All are healthy and normal.
SOCIOECONOMIC HISTORY
 Patient belongs low socioeconomic status
 Lives in cemented house
 Father is the only earner
 Hygienic conditions are satisfactory.
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.
DIFFERENTIAL
DIAGNOSIS
CLINICAL EXAMINATION
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.
vitals
 BP: 110/70 mmhg
 Pulse: 108 beats/minute
 R/R: 22breaths / minute
 Tem: 102F
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.
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
 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
 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
 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).
 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.
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.
INVESTIGATIONS
CBC
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 %
PERIPHERAL FILM
 Macrocytic ,normochromic red cells, platelets are normal in
film
 75% blast cells are seen.
X-RAY CHEST
Ultrasound REPORT
LFT , URINE DR
S.UREA CREATININE NORMAL
BlOOD CULTUR:
Pleural effusion DR
MRI-BRAIN
MRI BRAIN REPORT..
CERIBEROSPINAL FLUID DR
CSF ACID FAST BACILLI
SMEAR
LDH LEVEL
LDH level =538
BONE MARROW
BIOPSY
BONE MARROW
BIOPSY
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
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.
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.
CYTOGENETIC
REPORT OF BONE
MARROW
BONE
MARROW
CHROMOSOM
E
DIAGNOSIS
PRECURSOR- B CELL
ACUTE
LYMPHOBLASTIC
LEUKEMIA
with
Philadelphia
chromosome
CNS INVOLVEMENT
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.
STAGES of differentiation of B CELLS
AND THERE malignancies
CLASSIFICATION OF ACUTE LYPHOID
LEUKIMIA
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.
 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
Treatment
THERE ARE TWO COMPONENT OF
TREATMENT
SUPORTIVE TREATMENT
SPECIFIC TREATMENT
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 .
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.
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.
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.
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
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).
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.
Transplantation
 Hematopoietic stem cell transplantation
(HSCT) seems to be a valuable option for ALL
carrying poor prognostic factors.

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ACUTE LEUKEMIA ( asif rahman)

  • 1.
  • 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.
  • 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.
  • 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.
  • 29.
  • 31. LFT , URINE DR S.UREA CREATININE NORMAL
  • 34.
  • 35.
  • 36.
  • 40. CSF ACID FAST BACILLI SMEAR
  • 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.
  • 50.
  • 51.
  • 52.
  • 53.
  • 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
  • 56.
  • 57. CLASSIFICATION OF ACUTE LYPHOID LEUKIMIA
  • 58.
  • 59.
  • 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
  • 62.
  • 63.
  • 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.
  • 67.
  • 68.
  • 69.
  • 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.