HAEMATOLOGY PRESENTATION

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HAEMATOLOGY PRESENTATION

• TZE YENG YEOH
• MBChB II (2003)

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CASE 1 -1

• Mary, 31 year old lady.
• Presented to her GP with non-tender lumps in her
  neck. Otherwise, feeling well.
• Also feeling very fatigued.
• What are your differential diagnoses?

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CASE 1 -2

• GP commenced her on oral antibiotics for 3
  months.
• Lumps persisted.
• In the meantime, bloods were done.
• Bloods were found to be abnormal.
• Hence, she was referred to the haematologists at
  MMH.

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CASE 1 -3

• Hb 132
• RCC 4.33
• PCV 0.38
• MCV 87
• MCH 30.5
• Plt 307
• WCC 19.8 (?)
• Neut 6.7
• Monocytes 0.4
• Lymphocytes 6.9 (?)
• Smear cells 5.7 (?)
• Interpret the blood result. What do you think she
  has? What would you do now?

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CASE 1 -4
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CASE 1 -5

• Bone marrow aspirate and trephine confirmed CLL.
• Other tests done include
• Ig levels - Normal
• Serum electrophoresis Oligoclonal banding
  pattern in the gamma region.
• ?-2 microglobulin - ? 2.2 (1.3-2.2)
• Cytogenetics Loss of 17p13.1
• CT scan of neck, chest, abdo and pelvis
  Extensive lymphadenopathy in neck (with marked
  compression of airway), axilla, para-aortic
  region and around external iliac vessels and in
  the inguinal region. Also, left lung infiltration
  and splenomegaly.

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CASE 1 -6

• Commenced on fludarabine PO with co-trimoxazole.
  Taken for 4 months with no significant change in
  cervical lymphadenopathy.
• Had another CT scan which confirmed this.
• Had one episode of spontaneous bruising on
  abdomen and upper limbs. Also has frequent
  bleeding from gums.
• Had a bout of pneumonia recently. Recovered well
  with no complications.

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CASE 1 -7

• Treatment changed to prednisone and chlorambucil
  PO.
• Again, no significant change in cervical
  lymphadenopathy.
• Came to Day Stay to commence on IV chemotherapy.
  Unfortunately, she developed a significant
  neutropenia.

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CLL

• Accounts for 25 of leukaemias seen in clinical
  practice.
• Usually occurs in the elderly (? 60 years), with
  a male proponderance.
• Etiology is unknown but a familial tendency has
  rarely been observed.

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CLL PATHOLOGY

• It is known as a lymphoproliferative disorder.
• Accumulation of small, morphologically mature
  lymphocytes in bone marrow, lymph nodes,
  peripheral blood, spleen and liver.
• These are usually monoclonal B cells.
• Slow accumulation due to immunological
  non-reactivity and impaired apoptosis, rather
  than increased proliferation per se.

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CLL CLINICAL FEATURES

• Lymphocytosis on routine FBC.
• Symmetrical lymphadenopathy. Discrete and
  non-tender.
• Systemic symptoms.
• Symptoms of anaemia.
• Splenomegaly and/or hepatomegaly.
• Infections. (Which infections commonly?)
• Symptoms of thrombocytopoenia.

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CLL LAB FINDINGS -1

• FBC
• ? WCC due to lymphocytosis.
• Presence of smear cells.
• Normochromic, normocytic anaemia.
• ? platelets.
• Cell markers (from blood film or marrow)
• - To confirm monoclonal B cells. How?

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CLL LAB FINDINGS -2

• Bone marrow
• Lymphocytic infiltration 25-95 of all the
  cells.
• Biochemistry
• ? Ig.
• Paraprotein (rarely).
• Hyperuricaemia.

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CLL STAGING -1

• 2 systems Rai and Binet.

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CLL - RAI
Stage Features Median survival (months)
0 Lymphocytosis ? 15x109/L 150
I Lymphocytosis lymphadenopathy 105
II Lymphocytosis enlarged spleen and/or liver ? adenopathy 71
III Lymphocytosis anaemia ? adenopathy ? organomegaly 19
IV Lymphocytosis thrombocytopenia ? adenopathy ? organomegaly 19
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CLL - BINET
Stage Organ enlargement Hb (g/L) Platelets (x109/L)
A 0, 1 or 2 areas
B 3, 4 or 5 areas 100 100
C Not considered ? 100 ? 100
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CLL - MANAGEMENT

• Treat only if symptomatic, complications develop
  or disease is rapidly progressive.
• Aim is to control disease and not to cure.
• Treatment options include
• Prednisone
• Alkylating agents e.g. chlorambucil or
  cylcophosphamide (first line)
• Fludarabine (need to give co-trimoxazole
  prophylactically) (second line)
• Combination chemotherapy
• Radiotherapy

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CLL - COMPLICATIONS

• Bone marrow failure (pancytopenia)
• Autoimmune haemolytic anaemia.(How do you
  diagnose this?)
• Decreased immunoglobulins infections.
• ITP.
• Splenomegaly.
• Leukostasis. (rarely)

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CLL - PROGNOSIS

• Indolent condition usually.
• Most patients have a favourable prognosis.
• Unlike CML, CLL does not transform into an acute
  leukaemia.
• However, immunoblastic transformation may occur
  as a terminal lymphoma (Richters syndrome).
• Many elderly patients with CLL die with CLL
  rather than from it.
• Death from CLL usually caused by infection due to
  bone marrow failure and immune deficiency.

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CLL PROGNOSTIC MARKERS

• Age Young, good prognosis.
• Sex Female, good prognosis.
• Stage Early, good prognosis.
• Disease progression Slow, good prognosis.
• Response to treatment Resistant, bad.
• ?-2 microglobulin High, bad prognosis.
• Cell markers CD 38, bad prognosis
• Cytogenetics specific chromosomal mutations
  predict disease progression and median survival.

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CASE 2 -1

• A 69-year old lady presents with a 3-month
  history of fatigue and breathlessness.
• Physical examination revealed splenomegaly.
• Blood results are as follows

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CASE 2 -2

• Hb 9.0 g/dl
• MCV 90 fl
• Platelets 500 x 109/l
• Total WBC 200 x 109/l
• White cell differential count
• Blasts 3 Promyelocytes 6 Myelocytes 12
  Metamyelocytes 6 Neutrophils 55 Eosinophils
  4 Basophils 4 Lymphocytes 5 Monocytes 5
• What do you think?

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CASE 2 -3
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CML - INTRODUCTION

• Is a myeloproliferative disorder.
• Comprises ? 20 of all the leukaemias.
• Seen most frequently in middle aged people, but
  can occur at any age.
• MF 1.41
• No predisposing factors in most cases.
• 3 cardinal features
• Splenomegaly
• Leucocytosis myeloid series with blasts
  through to neutrophils
• Bcr-abl gene/Ph chromosome

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CML PATHOLOGY -1

• Acquired abnormality of haematopoietic stem
  cells.
• Myeloid proliferation with expansion of normal
  marrow, splenomegaly and peripheral blood
  leucocytosis.
• Abnormality is due to reciprocal translocation
  between chromosomes 9 and 22.
• This leads to formation of a fusion or hybrid
  gene (bcr-abl), known as the Ph chromosome.
  (basis of the diagnostic test for CML)

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CML PATHOLOGY -2

• This new gene codes for an active tyrosine kinase
  which continuously switches on the haemopoietic
  stem cell.
• The Ph chromosome is present in most haemopoietic
  cell lineages, i.e. RBCs, megakaryocytes,
  basophils, monocytes and B cells.
• About 5 of people with CML will lack the Ph
  chromosome. However, at a DNA, RNA and protein
  level, the molecular pathology with formation of
  the bcr-abl gene is still present.

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CML PATHOLOGY -3

• Ph chormosome can also be found in some ALL and
  AML.

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CML CLINICAL FEATURES

• 20 asymptomatic.
• Splenomegaly.
• Hypermetabolism symptoms e.g. weight loss,
  lassitude, anorexia or night sweats.
• Features of anaemia.
• Features of abnormal platelet function.
• Gout or renal impairment hyperuricaemia.
• Infections usually when neutropoenic.

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CML LAB FINDINGS -1

• FBC
• Leucocytosis with left shift.
• ? basophils.
• Platelets ?, normal or ?. Giant platelets.
• Normochromic, normocytic anaemia.
• Bone marrow biopsy
• Hypercellular, with granulopoietic predominance.
• Ph chromosome.
• NAP score
• - Low.

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CML LAB FINDINGS -2

• Cytogenetics
• In bone marrow and/or peripheral blood (FISH)
  bcr-abl gene/Ph chromosome.
• Biochemistry
• ? serum B12 and B12-binding capacity.
• ? serum uric acid.

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CML - PHASES

• Chronic
• Accelerated
• Blast crisis Transforming to acute leukaemia,
  usually AML.

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CML MANAGEMENT -1

• Chronic phase
• Hydroxyurea shorter action. Requires frequent
  monitoring and continuous therapy.
• ?-interferon Low platelets, depression.
• Cytosine arabinoside.
• Glivec (imatinib) specific inhibitor of
  abnormal tyrosine kinase. Less useful in blast
  crisis.

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CML MANAGEMENT -2

• ? Allogenic BMT Potential cure. Only for those
  55 years and with a HLA-matched donor.
• Accelerated phase and blast crisis
• ? Harder to treat as patient becomes refractory
  to therapy.

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CML - PROGNOSIS

• Chronic phase 5-6 years, if treated. Usually
  shows an excellent response to chemotherapy.
• Accelerated phase Few months.
• Blast crisis Few months.
• Rough guides to outcome include age, spleen size,
  platelet count, blast cell percentage on
  presentation degree of response to therapy.
• Death is usually due to terminal acute
  transformation or from intercurrent haemorrhage
  or infection.

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