Case Presentation

1. 

2. Dr. Moeez Qaiser
PGR M lll, SHL

3. 
 A 22 years old female Yasmin resident of Lahore
presented with complaints of :
Fever (off and on) 3 months
Productive Cough 3 months
Shortness of Breath 1 & Half month
Presenting Complaints

4. 
 Tuberculosis
 Recurrent Pneumonia
 Lung abscess
 Anemia
 Lymphoproliferative disorders.
 Malignancy
 Autoimmune Connective tissue disorders
Differential Diagnosis

5. 
Fever was:
 Gradual in onset
 Low grade
 Intermittent
 More at night
 Doc. as 100-101 F
 Relieved only temporarily by anti-pyretics
 No specific aggravating factors
History Of Present illness

6.  Associated with:
 Rigors and chills
 Night sweats
 Anorexia
 Weight loss
( 5 Kg over 3 months)
 Easy fatigueability
 Generalized body aches/
pains
 Cough with sputum
 Pain abdomen off and
on
 Shortness of Breath
Fever was
Not associated with:
• Vomiting
• Loose motion
• Ear discharge
• Dysuria/Burning
micturition
• Rash/spots on any part of
the body
• Any mucosal bleed

7. 
 Moderate in severity
 More at night
 Productive
 Quarter a cup , odorless
 Yellowish
 No hemoptysis
 Relieved By Cough syp.
Cough was

8.  Gradual in onset
 Progressive
 Aggravated by exertion
 Associated with:
Palpitations
Productive cough
Not Associated with:
Orthopnea
Paroxysmal nocturnal dyspnea
Chest pain
Shortness of breath:

9. H/O:
2-3 blood transfusions
TB contact – Father
No H/O:
Smoking
IV drug abuse
Asthma
Animal contact
Any foreign travel
No H/O joint pains
No H/O any S.Abortion

10. Occupational History:
Housewife
No h/o any radiation exposure
Family history:
Mother – Diabetic
Father – TB (5 yrs back) – Took ATT(9 Mo)
Menstrual History:
Age of Menarche : 13 yrs
30/5 cycle , Regular
History:

11. 
Surgical History
C-Section – 2 times
Drug History:
Antipyretics (Panadol)
Antitussives
Antibiotics
ATT (5 days) then quit

12. 
 Tuberculosis
 Recurrent Pneumonia
 Anemia
 Lymphoproliferative disorders.
 Malignancy
Differential Diagnosis

13. 
An ill looking young female with average built oriented in
time, place and person with following vitals:
 Pulse: 102/min Regular
 B.P: 110/70
 R/R: 20/min
 Temp: 99 F0
Examination:

14. 
 Pallor++
 Clubbing 0
 Cyanosis 0
 Jaundice 0
 Pedal oedema 0
 A single anterior cervical lymph node palpable B/L
Axillary and Inguinal lymph nodes were not palpable
 Lymph nodes were non-tender, rubbery in consistency, not
attached to overlying skin, having no discharge or sinuses.

15. 
No significant abnormal findings
found in Respiratory and Cardio-
vascular system.

16. 
Abdomen was soft non-tender
Liver palpable
B/S were audible.
GIT

17. 
 GCS 15/15
Grossly intact
 Low mood
 No focal or neurological deficit
CNS

18. 
A 22 year old female presented with 3 months h/o fever,
productive cough and progressive shortness of breath
associated with pallor, lymph-adenopathy and
Hepatomegaly ..
Summary

19. 
 Lymph proliferative disease
 Tuberculosis
Differential Diagnosis:

20. 
Investigation

21. 
 HGB – 4.6 gm/dl
 WBC - 6.6 , N:74% L:20% M:5% E:1%
 Platelets – 39
 HCT - 15
 MCV – 85%
 ESR – 160
CBC

22. 
 Blast cells 55%
 Myelocytes 30%
 Neutrophils 21%
 Lymphocytes 20%
 Monocytes 1%
 Retic count 1.4%
Peripheral Smear

23. 
LFTS – Normal
RFTS – Normal
S/E – Normal
Coagulation Profile –
PT :13
INR : 1.4
APTT : 33
Urine C/E – Normal

24. 
 Malarial Parasite Slide : -ve
 Blood Culture & Sensitivity : awaited
Sputum For AFB : -ve

25. 
Serum Iron : 41ug/dl
TIBC : 175%
Transferrin sat . : 23.4%
LDH – 270 U/L
Uric Acid – 3.9
Viral Serology –ve
Fecal occult blood –ve

26. 
CXR - Normal
USG – Liver size 18cm
Spleen size 10cm

29. 
Lymph node Biopsy report awaited

30. 
AML ( Acute Myeloid leukemia )
Final Diagnosis

31. 
Decision about treatment depends on clinical stage,
prognostic factors and patient condition
Treatment

32. During her stay
 After the reports, the nature of illness, treatment
options and prognosis was explained.
 Discharged and refered to Oncologist

34. Epidemiology
 Incidence -3.5 per 100,000 people per year
 Median age at diagnosis- 67 years
 AML incidence increases with age

35. Hematopoietic
stem cell
Neutrophils
Eosinophils
Basophils
Monocytes
Platelets
Red cells
Myeloid
progenitor
Lymphoid
progenitor
B-lymphocytes
T-lymphocytes
Plasma
cells
naïve
ALL
AML

36. Etiology
 Heredity
 Down syndrome
 Fanconi anemia
 Bloom syndrome
 ataxia-telangiectasia
 Congenital neutropenia (Kostmann syndrome)
 Radiation
 High-dose radiation (atomic bombs survivors)

37.  chemical and occupational exposures
 Benzene
 petroleum products
 Paint
 embalming fluids
 ethylene oxide
 Herbicides
 smoking


38.  Drugs
 Alkylating agent
 Topoisomerase II inhibitor
 Chloramphenicol
 Phenylbutazone
 Chloroquine
 methoxypsoralen

39. Clinical Presentation
 Nonspecific symptoms
 Fatigue
 Anorexia
 Weight loss
 Fever
 Bleeding, easy bruising
 Bone pain, lymphadenopathy, nonspecific cough,
headache, or diaphoresis

40. Physical Findings
 Fever
 Splenomegaly
 Hepatomegaly
 Lymphadenopathy
 Sternal tenderness
 Evidence of infection and hemorrhage

41. Gum hypertrophy

42. Diagnostic procedure
 Morphology
 cytochemistry
 Immunophenotyping
 Cytogenetics
 Molecular cytogenetics
 Molecular genetics

45. Bone marrow in acute leukemia
 Necessary for diagnosis
 Useful for determining type
 Useful for prognosis
 Acute leukemias are defined by the presence of >
20% blasts in bone marrow (% of nucleated
marrow cells)

46. Auer rods in AML

47. Pretreatment EvaluationInitial Diagnostic Evaluation and Management of Adult Patients with AML
History
Increasing fatigue or decreased exercise tolerance (anemia)
Excess bleeding or bleeding from unusual sites (DIC, thrombocytopenia)
Fevers or recurrent infections (granulocytopenia)
Headache, vision changes, nonfocal neurologic abnormalities (CNS leukemia or bleed)
Early satiety (splenomegaly)
Family history of AML (Fanconi, Bloom, or Kostmann syndromes or ataxia-telangiectasia)
History of cancer (exposure to alkylating agents, radiation, topoisomerase II inhibitors)
Occupational exposures (radiation, benzene, petroleum products, paint, smoking,
pesticides

48. Physical Examination
Performance status (prognostic factor)
Ecchymosis and oozing from IV sites (DIC, possible acute promyelocytic leukemia)
Fever and tachycardia (signs of infection)
Papilledema, retinal infiltrates, cranial nerve abnormalities (CNS leukemia)
Poor dentition, dental abscesses
Gum hypertrophy (leukemic infiltration, most common in monocytic leukemia)
Skin infiltration or nodules (leukemia infiltration, most common in monocytic leukemia)
Lymphadenopathy, splenomegaly, hepatomegaly
Back pain, lower extremity weakness [spinal granulocytic sarcoma, most likely in t(8;21)
patients]

49. Initial Diagnostic Evaluation and Management of Adult Patients with AML
Laboratory and Radiologic Studies
CBC with manual differential cell count
Chemistry tests (electrolytes, creatinine, BUN, calcium, phosphorus, uric acid, hepatic
enzymes, bilirubin, LDH, amylase, lipase)
Clotting studies (prothrombin time, partial thromboplastin time, fibrinogen, D-dimer)
Viral serologies (CMV, HSV-1, varicella-zoster)
RBC type and screen
HLA typing for potential allogeneic HSCT
Bone marrow aspirate and biopsy (morphology, cytogenetics, flow cytometry, molecular
studies for NPM1 and CEBPA mutations and FLT3-ITD)
Cryopreservation of viable leukemia cells
Echocardiogram or heart scan
PA and lateral chest radiograph
Placement of central venous access device

50. Initial Diagnostic Evaluation and Management of Adult Patients with AML
Interventions for Specific Patients
Dental evaluation (for those with poor dentition)
Lumbar puncture (for those with symptoms of CNS involvement)
Screening spine MRI (for patients with back pain, lower extremity weakness,
paresthesias)
Social work referral for patient and family psychosocial support
Counseling for All Patients
Provide patient with information regarding their disease, financial counseling, and
support group contacts.

51. Prognostic Factors
 Age at diagnosis
 Chronic and intercurrent diseases
 Performance status
 A prolonged symptomatic interval with cytopenias
preceding diagnosis
 A high presenting leukocyte count
 Chromosome findings at diagnosis*
 Achievement of CR
 Secondary AML

52. Principles of treatment
 Combination chemotherapy
 First goal is complete remission
 Further rx to prevent relapse
 Supportive medical care
 Transfusions, antibiotics, nutrition
 Psychosocial support
 Patient and family

53. Complete remission
CR is defined-
 Blood neutrophil count -1000/L
 Platelet count 100,000/L.
 Circulating blasts - absent.
 The bone marrow <5% blasts
 Auer rods -absent.
 Extramedullary leukemia -absent

54. Management: Acute Myeloid
Leukemia

55. Induction Chemotherapy
 Cytarabine is usually administered as a
continuous intravenous infusion for 7 days
 Anthracycline therapy generally consists of
daunorubicin intravenously on days 1, 2, and 3
(the 7 and 3 regimen).
 Etoposide

56. Postremission Therapy
 Postremission therapy is designed to eradicate
residual leukemic cells to prevent relapse and
prolong survival

57.  Intensive chemotherapy
 High-dose cytarabine 4 cycles of HiDAC
(3 g/m2 per q12h on days 1, 3, and 5)
 Allogeneic or autologous HSCT

58.  Patients who fail to attain CR after two induction
courses should be treated with an allogeneic
hematopoietic stem cell transplant (HSCT)

59. Hematopoietic stem cell
transplantation
• Permits “rescue” from otherwise excessively
toxic treatment
• Additional advantage of graft-vs-leukemia
effect in allogeneic transplants
• Trade-off for allogeneic transplantation:
greater anti-leukemic effect but more toxic

60. Management of special situations

61. Hyperleukocytosis
• Hyperleukocytosis with leukostasis immediate medical
treatment.
• Leukapheresis
• Hydroxyurea, given at dosages up
– 50 to 60 mg/kg per day.
– Until the wbc has been reduced.
• Prevention of tumor lysis syndrome
– Hydration,
– Control of uric acid production using allopurinol or rasburicase
– Control of urine ph

62. CNS involvement
• Less than 5% of patient
• Intrathecal cytarabine
• Dexamethasone to prevent arachnoiditis

63. Supportive Care

64. Prophylactic anti-infectious treatment
• Personal hygiene
• Dental hygiene
• Vigorous hand washing
• Anti-fungal prophylaxis
• Antibiotic prophylaxis
Leibovici L, Paul M, Cullen M, et al. prophylaxis in neutropenic patients. New
evidence, practical decisions.Cancer.2006;107(8):1743-1751.

65. Transfusion support
• Prophylactic platelet transfusions-
• hemoglobin level above 8 g/dL
• Prevent alloimmunization
• Gamma irradiation (at least 25 Gy)
Schiffer CA, Anderson KC, Bennett CL, et al. transfusion for patients with cancer:
clini-cal practice guidelines of the American Clinical Oncology.J Clin
Oncol.2001;19(5):1519-1538.

66. Selected New Agents under Study for the Treatment of Adults with
AML
Class of Drugs Examples of Agents in Class
Tyrosine kinase inhibitors PKC412, MLN518, SU11248, CHIR-258,
imatinib (STI571, Gleevec), dasatinib,
AMN107
Demethylating agents Decitabine, 5-azacytidine
Histone deacetylase inhibitors Suberoylanilide hydroxamic acid (SAHA),
MS275, LBH589, valproic acid
Heavy metals Arsenic trioxide
Farnesyl transferase inhibitors R115777, SCH66336
HSP-90 antagonists 17-allylaminogeldanamycin (17-AAG), DMAG,
or derivatives
Cell cycle inhibitors Flavopiridol, CYC202 (R-Roscovitine), SNS-032
Toxin-conjugated antibodies Gemtuzumab ozogamicin
Proteasome inhibitors Bortezomib
Aurora inhibitors AZD1152, MLN-8237, AT9283
Immunomodulatory Lenalidomide, IL-2, histamine
dihydrochloride