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Case Discussion

Presenter: Dr. Anisha Mathew

Moderator: Dr. Sarama Saha
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History
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Chief Complaints: 20 year old male patient
 Fatigue x 2 months
 Loss of appetite x 3 months
 Weight loss x 5 months

Other significant History:

 Occasional Bidi smoker x 4 years
• No significant family history
• No other significant history
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General Physical Examination
• Conscious Oriented
• Thin Built
• Afebrile
• Weight: 40 Kg Height: 170 cm BMI: 13kg/𝑚2
• Pallor +++
• No Clubbing/ Icterus/ Cyanosis/ LAP/ Edema
• HR: 98 bpm
• BP : 128/86 mmHg
4 Systemic Examination
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Cardiovascular system, Respiratory System and Central

nervous system: WNL

Abdominal examination:
 Appears to be of normal shape and contour, all
quadrants rising equally with respiration, no tenderness,
gaurding
 Spleen enlarged, 8 cm below costal margin

 No other organomegaly
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Possible Diagnosis?
Other d/d’s?
6 Laboratory Reports
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Hematological: Peripheral Blood

 Hb: 8.9 gm/dL
smear:
 Blasts7, PM4, My28,
 RBC: 3.97 x 103/L
MM10
 TLC: 2.9 lakhs/mm3  Reticulocytes: 1.7%
 DLC: N34 L3 M2 E4 B8 ,
Platelets: 5.03 lakhs/mm3
 MCW: 63.5 MCH: 21.1
MCHC: 33.2
 RDW: 21.0
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Laboratory Reports

Coagulation Profile: Other tests:

 APTT: 28.8s (C=25.25s)  Ferritin: 349 mg/dL

 PT: 14.6s (C=109s)  S.Iron: 46 mg/dL

 INR: 1.29  B12: 894

 Fibrinogen: 245 mg/dL  Folate:10.9

 D-Dimer >5.5mg/dL  LDH: 996 UL

 LFT/KFT: WNL
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Molecular testing
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BCR-ABL q-PCR :
 Normalized copy number (NCN): 63.68

 International Scale-NCN(IS-NCN): 34.39

Clinical Scoring

 Sokal : High risk

 Hasford: Intermediate Risk

 EUTOS: High Risk

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Final Diagnosis
Plan of next step
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Current Status of patient

 Patient was being planned for bone marrow

aspiration to start treatment on Imatinib
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Theory of CML
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Cause, Diagnosis and Treatment
12 Chronic Myeloid Leukemia
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• Clonal hematopoietic disorder caused
by an acquired genetic defect in a
pluripotent stem cell
Pluripotent stem cell disease
characterized:
 Anemia

 Extreme blood granulocytosis and

granulocytic immaturity
 Basophilia

 Thrombocytosis

 Splenomegaly
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Epidemiology

 15% of all Leukemia cases

 Sparse Indian data

 Male pre-dominanace

 Age of presentation: 15-60 years of age

 Only known risk factor for the development of CML is

exposure to radiation at high doses
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Etiopathogenesis

 Very High doses of ionizing radiation

 Chemical leukemogens: benzene / alkalizing agents

 Several large studies: no links with smoking/ diet/ lifestyle

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Pathophysiology
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Philadelphia chromosome
 Present in >80% of CML
patients
 Reciprocal translocation
between the long arms of
chromosomes 9 and 22,
t(9;22) (q34;q11)
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Pathophysiology of CML
17 Phases of CML
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Diagnosis
Clinical Manifestations
 90% are diagnosed in the chronic or stable phase
 More recent series: elevated white blood count on routine
blood sampling
 Most common presenting symptoms of CML are related to
anemia, splenomegaly, and increased cell turnover
 Patients may present with a hyperviscosity syndrome
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Diagnosis
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Peripheral Blood Bone Marrow

 A full spectrum of  Markedly hypercellular, with
myeloid cells from blasts a predominance of myeloid
to neutrophils cells with full maturation
 Blasts <15% ; usually  Blasts <15% and basophilia
less than 5% of the WBC is also present
differential  Megakaryocytes are
 Basophilia is invariably usually increased in
present number associated with
erythroid hypoplasia
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Diagnosis
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Peripheral Blood Bone Marrow

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Molecular Diagnosis

 Diagnosis of CML requires presence of BCR-ABL

 BCRABL fusion gene detectable by fluorescence in

situ hybridization (FISH) or Reverse Transcription–
polymerase chain reaction (RT-PCR)
22 Molecular Diagnosis
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FISH
 Colocalization of large,
fluorescently labelled genomic
probes
 Performed on metaphase or
interphase cells and on
peripheral blood
 Highly accurate but less
useful in low burden disease
due to random colocalization
RT-PCR
 Amplify the unique
sequences created by the
fusion of BCR and ABL
 Ideal for the detection of
minimal residual disease
 Quantitative RT-PCR is
preferred for monitoring and
may allow for the early
detection of resistance to
therapy
 Both false +/false - possible
23 Molecular Diagnosis
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FISH RT-PCR
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Scoring systems
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Treatment

 Response to therapy : monitoring of blood counts, cytogenetics,

and real-time quantitative polymerase chain reaction (RQ-PCR).
 Tyrosine Kinase Inhibitors (TKIs) are standard frontline therapy
for newly diagnosed patients with chronic phase CML
 Hydroxyurea, a well-tolerated oral agent

 Allogeneic Hemopoietic cell transplantation (HCT), typically for

patients with resistance to TKI therapy or CML-AP patients
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Prognosis
Patient responses are normally assessed at 3, 6, and 12 months
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