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A case of Chronic Myeloid Leukemia
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  • 1. A Case of CML By Dr. P. Arul M 7 Unit Prof. Dr. P. Vijayaraghavan’s unit
  • 2.
    • 45 yr old female, kaveri, from redhills was admitted with complaints of
      • Abdominal distention – 6 months
      • Leg swelling – 4 months
      • urine output – 4 months
    • h/o present illness:
      • Patient was apparently normal 6 months back
      • She developed a swelling in the left hypochondrium that progressed to the present size
      • She developed bilateral leg swelling and decreased urine output for the past 4 months
  • 3.
    • She gives h/o
      • Fever – low grade, intermittent, not associated with chills or rigors, for the past 6 weeks
      • Loss of appetite
      • Loss of weight
    • There is no h/o
      • Nausea, vomiting
      • Heart burn
      • Jaundice
      • Abdominal pain
      • Hematemesis, melena
      • Hematochezia or bleeding PR
      • Alteration in bowel habit
      • Neuropsychatric manifestation
  • 4.
    • Past history :
      • Patient is not a known case of diabetes, hypertension, tuberculosis, epilepsy, bronchial asthma
    • Personal history:
      • Not a tobacco chewer
      • Not a smoker or alcoholic
      • No h/o chemical/ radiation exposure
    • Family history:
      • No h/o any malignancy among family members
    • Contact history:
      • No h/o contact with patients with tuberculosis
  • 5.
    • General examination
      • Conscious
      • Oriented
      • Afebrile
      • Not Dyspnoeic
      • Hydration Fair
      • Pallor+
      • Pedal edema+
      • Axillary, cervical, inguinal lymph nodes – palpable, firm, non tender, size ranging 0.5 to 1 cm
    • Vitals
      • Pulse rate: 80/min
      • Blood pressure: 100/70 mmHg
      • Temperature: 98.4 F
      • Respiratory rate: 16/ min
  • 6.
    • Systemic examination
      • Upper GIT: Normal
      • Inspection:
        • Shape - distended
        • Flanks - free
        • Dilated veins - upper part of abdomen
        • Umblicus - pushed downwards
        • Skin - normal
        • Hernial sites - normal
        • A mass extending from left hypochondrium to the hypogastric region seen, it moves with respiration
  • 7.
    • Palpation
      • Superficial
        • Normothermic
        • No tenderness, hyperaesthesia
        • Direction of flow of veins – away from the umblicus
        • No divarication of recti
        • No abnormal pulsation
      • Deep
        • Liver 4.5 cm below RCM, firm, smooth surface, moves with respiration, non tender
        • Spleen 19 cm below LCM, towards RIF, firm, non tender, smooth surface, edges well defined
        • No other mass palpable
  • 8.
    • Percussion
      • No free fluid
      • Upper border of liver dullness: 5 th ICS
      • Upper border of spleenic dullness 8 th ICS
    • Auscultation
      • Bowel sounds+
      • No hepatic or spleenic rub
      • No venous hum
      • No bruit
    • PR – not done
  • 9.
      • Blood group – A+ve
      • Total count – 1,40,000
      • Differential count – P-98, L-02, E/B-0
      • Platelets – 34, 000
      • Sugar 80 mg%
      • Urea 43 mg%
      • Creatinine 1.2 mg%
      • Hiv – neg
      • Hbsag – neg
      • Anti HBC – neg
    Investigations
  • 10.
      • Hb – 5.6 g/dl
      • PCV – 19.1
      • MCV – 84.1
      • MCH – 24.7
      • MCHC – 29.3
      • ESR 102/hr
      • PT
        • Control – 12-15s
        • Test 14s
        • INR 1.0
      • APTT
        • Control – 26s
        • Test – 26s
      • Bilirubin
        • Total – 1.34
        • Direct – 0.98
      • AST - 23U/L
      • ALT - 10U/L
      • GGT - 77U/L
      • SAP - 567U/L
      • Proteins
        • Total – 5.6 g/dl
        • Alb – 2.9 g/dl
        • Glo – 2.7 g/dl
      • Na+ 124.6
      • K+ 5.4
      • Cl- 95.7
  • 11.
    • Urine
      • colour – pale yellow
      • Appearance – clear
      • pH – 6.5
      • Specific gravity – 1.020
      • Alb – trace
      • Sugar – neg
      • Blood – neg
      • ketone – neg
      • Bilirubin – neg
      • Urobilinogen – N
      • Nitrite – neg
    • Urine microscopy
      • Leucocytes 1-2/hpf
      • Epithelial cells – occasional
      • RBC – not seen
      • Other cells – not seen
  • 12. Peripheral smear
  • 13. Peripheral smear
    • RBC
      • Normocytic hypochromic
      • Few cells are microcytic, hypochromic with anisopoikilocytosis
      • Few normoblasts seen
    • WBC
      • Increased
      • Myeloblasts 10%
      • Promyelocytes 20%
      • Lymphocyte 40%
      • Mature neutrophils 20%
      • Stab form 4%
      • Basophil 4%
      • Eosinophil 2%
    • Platelets – reduced
    • No parasites
  • 14. Bone marrow examination
    • Hypercellular marrow – erythroid series normal
    • Myeloid erythroid ratio 9:1
    • Megakaryocytes reduced
    • Myeloid series increased with increase in lymphoblasts
      • Lymphoblasts 46%
      • Myeloblasts 10%
      • Promyelocytes 24%
      • Mature neutrophils 16%
      • Stab forms 2%
      • Basophil 1%
      • Eosinophil 2%
    • IMP: CML with lymphoid blast crisis
  • 15.
      • ECG – normal
      • CXR – normal
      • BT – 2’ 15’’
      • CT – 3’
      • USG abdomen
        • Hepatospleenomegaly
    • Medical oncologist opinion obtained
    • Treatment
      • symptomatic
  • 16. Chronic Myeloid Leukemia
    • Incidence
      • 1.5 per 100,000
      • Men>women
      • Age usually after middle forties
    • Etiopathogenesis
      • Large doses of radiation can cause CML
    • What is CML?
      • Overproduction of myeloid cells
      • The myeloid cells retain the capacity of differentiation and bone marrow function in early phase
      • Stable for years
      • Philadelphia chromosome – reciprocal translocation between long arm of chromosome 9 and 22
      • Large portion of 22q is translocated to 9q and a smaller portion of 9q is moved to 22q
      • 9q has the proto oncogene ‘abl’
      • Abl is received at a specific site on 22q the bcr (break point cluster)
      • Fusion of bcr/abl produces a novel protein that possess tyrosine kinase activity
  • 17.
    • Disease progression is due to
      • Chromosomal instability of the malignant clone
      • Large deletions adjacent to the translocation break point
      • Hetrogenous structural alterations of the p53 gene
      • Presence of altered ‘myc’ gene
    • The disease progress to chronic phase, accelerated phase and blast crisis
  • 18.
    • Clinical features
      • Middle age most affected
      • Fatigue
      • Night sweats
      • Low grade fever
      • Abdomen fullness
      • Symptoms of leucostasis
        • Blurred vision
        • Respiratory distress
        • Priapism
    • Physical findings
      • Spleen enlarged
      • Hepatomegaly – occationally
      • Sternal tenderness
      • Increasing spleen size occurs in accelerated phase
  • 19.
    • Investigations
      • Increase in white cell count
      • Increase in immature and mature granulocyte
      • Myelocytes metamyelocytes and band forms are the majority
      • Platelets increased
      • Normocytic normochromic anemia
      • LAP decreased
      • Vitamin B12 increased
      • In bone marrow – cellularity in increased with increase in myeloid to erythroid ratio. Blast percentage is normal or increased.
      • Both in blood and bone marrow – basophils, monocytes, eosinophils are increased in number
      • Hall mark is the identification of bcr/abl by PCR
  • 20.
    • Disease acceleration
      • Increasing degrees of anemia
      • Cytogenetic clonal evolution
      • Blood or marrow blast between 10-20%
      • Blood or marrow basophils > 20%
      • Blood or marrow platelets < 100,000
    • Blast crisis
      • Acute leukemia with blood or marrow blasts > 20%
      • Hyposegmented neutrophils may appear
      • Extramedullary blast proliferation
      • Large foci of clusters of blasts in marow
  • 21. Differential diagnosis N N N or Essential thrombocytosis N N or N or Polycythemia vera abn or N or N or or N or Myelofibrosis N N or N CML Red cell morphology Platelets Hematocrit WBC
  • 22.
    • Not usually given till WBC >200,000/cumm
    • In case of priapism, respiratory distress, visual blurring emergency leukaparesis done with myelosuppressive treatment
    • Imatinib mesylate
      • Inhibit tyrosine kinase activity
      • 400 mg/day
      • Complete hematologic remission after 18 months was 97%
      • Cytogenetic remission rate 76%
      • Progression to accelerated and blast crisis is 3%
      • ADVERSE EFFECTS: Nausea, fluid retention, diarrhea, muscle cramp, skin rashes
    • Other drugs
      • Nilotinib
      • Dasatinib
      • INF alpha
    Treatment
  • 23.
      • Allogenic SCT
        • Indicated for failure to respond to imatinib or when patient is in accelerated or blastic phase of the disease
      • Hydroxyurea
        • Rapid lowering of WBC, reduction of symptoms and reversal of spleenomegaly
      • Busulphan
        • Not used due to side effects
      • Leukapharesis
        • Inensive leukapharesis may control blood counts in chronic phase of CML
        • Used in leucostasis related complications
        • Rx of pregnant women
      • Spleenectomy
        • Reserved for painful spleenomegaly and spleenomegaly unresponsive to imatinib chemotherapy or severe anemia, thrombocytopenia associated with hyperspleenism
    Treatment cont.
  • 24. What is hematologic response, molecular response and cytogenetic response
    • Hematologic response
      • Platelet count <450 x 10 9 /L
      • WBC < 10 x 10 9 /L without immature granulocytes and with less than 5% basophils
      • Non palpable spleen
    • Cytogenetic response
      • Complete ph+ 0%
      • Partial ph+ 1-35%
      • Minor ph+ 36-65%
      • Minimal ph+ 66-95%
    • Molecular response
      • Complete ph 0%
      • Partial ph+ non quantifiable and non detectable
      • Major ph+ <0.10%
  • 25. What is failure of treatment Loss of Complete Hematologic Response, loss of complete cytogenetic response + mutation Anytime Less than complete cytogenetic response 18 months after diagnosis Less than partial cytogenetic response 12 months after diagnosis Less than Complete Hematologic Response, no cytogenetic response 6 months after diagnosis No Hematologic Response 3 months after diagnosis Criteria Time
  • 26. Prognosis 0.0413 x eosinophils NA Blood eosinophils 0.20399 when basophils>3% NA Blood basophils 0.0584 x myeloblasts 0.0887 x (myeloblast – 2.10) Blood myeloblast % 1.0956 when platelet count >1500 x 10 9 /L 0.188 x [(platelet /700) 2 - 0.563] Platelet count x 10 9 /L 0.042 x spleen 0.0345 x (spleen–7.51) Spleen 0.666 when age >50 yrs 0.116 x (age-43.4) Age Hasford system Sokal index 781 – 1480 0.8 – 1.2 Intermediate > 1480 > 1.2 High < 780 < 0.8 Low Relapse rate
  • 27. Thank you