Lecture 6 - Leukemia - What You Need To Know

Question 1

Presenting features of leukemia

Answer 1

• lack of normal heamopoiesis: causes bone marrow failure. Anemia, neutropenia, thrombocytopenia
• excess malignant blood cells: high WCC causes hyperviscosity, increase in size of organs, bone pain in children
• acute: rapid onset of symptoms over days or weeks - no opportunity for the body to compensate
• chronic: slow onset of symptoms over weeks or months - physiological compensation possible for some symptoms

Question 2

Myeloid leukemia

Answer 2

• genetic mutations in the stem cell compartment cause pathological changes in cell proliferation and differentiation

Question 3

Acute myeloid leukemia

Answer 3

• proliferation with minimal differentiation
• BM: excess blasts
• PB: decrease normal cells +/- blasts

Question 4

Myeloiproliferatin

Answer 4

• proliferation with normal differentiation
• BM: increased cell numbers
• PB: increased cell numbers
• proliferation of granulocytes: CML

Question 5

Myelodysplasia

Answer 5

• proliferation with abnormal differentiation
• BM: increased or decreased cell numbers
• PB: normal or decreased cell numbers. Hypofunctional cells

Question 6

Acute myeloid leukemia

Answer 6

• proliferation of primitive white cells that lack differentiation, myeloblasts, in the BM with the rapid development of bone marrow failure
• pancytopenia with blasts present or absent
• definitive diagnosis requires bone marrow biopsy

Question 7

Bone marrow biopsy for AML

Answer 7

• bone marrow biopsy taken from iliac crest or sternum
• aspirate: cells in suspension
• trephine: bone core
• morphology: excess of myeloblasts
• genetics: examine chromosome number and structure
• surface proteins: immunophenotype of cell by flow cytometry

Question 8

AML management - fitness of the patient for treatment is important to assess: if young and fit

Answer 8

• rapid onset of BMF
• high dose chemotherapy to achive remission
• further chemotherapy or bone marrow transplantation for cure
• months in hospital for transfusion/infection

Question 9

AML management: if old or unfit

Answer 9

• palliation to maintain QoL
• low dose chemotherapy
• supportive care: blood transfusion and antibiotics
• overall 5 year survival is 25%

Question 10

Chronic myeloid leukemia

Answer 10

• proliferation of myeloid cells in blood and bone marrow with relatively normal differentiation
• hematopoiesis is effective
• anemia not a feature
• bone marrow overactivity
• elevated WCC

Question 11

CML three phases

Answer 11

1) chronic: usually lasting 2-4 years
2) accelerated phase: 6-12 months
3) acute phase or blast crisis (2-4 months). Similar to acute leukemia

Question 12

CML presentation

Answer 12

• median age at presentation is 45-55 years old
• at presentation 30% diagnosed by routine lab test, 85% diagnosed during chronic phase
• symptoms: fatigue, weight loss, abdominal fullness, hyperviscosisty

Question 13

Lymphoid malignancies

Answer 13

• predominantly in bone marrow and blood - leukemia

- predominantly in lymph nodes - lymphoma

Question 14

ALL vs CLL

Answer 14

• ALL: prliferation with minimal differentiation, excess blasts in BM, decreased normal cells and blasts in PB. Rapid onset of bone marrow faiure
• CLL: proliferation with differentiation: increase mature lymphocytes in BM and PB

Question 15

ALL characteristics

Answer 15

• commonest childhood cancer
• treated with combination chemotherapy given IV/intrathecally and radiation. Complex chemotherapy programs that last 2-3 years
• childhood cure rate 85-90%
• adult ALL is rare. Treated with chemotherapy with consideration of bone marrow transplantation in younger and fitter individuals. Overall 5 year survival is 65%

Question 16

CLL characteristics

Answer 16

• accumulation of mature lymphocutes in blood and BM - no features of BM failure
• indolent disease of the elderly
• rare in asian communities
• 25% of patients are asymptomatic when a routine blood count reveals an absolute lymphocytosis
• 87% lymphadenopathy (firm, round, non tender, mobile)
• 54% splenomegaly
• 30% marked lymphocytosis and anemia
• suscpetibility to infection

Question 17

• investigations for CLL

Answer 17

• FBC: absolute lymphocytosis. Anemia and thrombocytopenia associated with advanced disease
• blood film: mature small lymphocytes and smudge cells
• flow cytometry: clonal B cell pop: one light chain, B cell markers (CD19,20) with aberrant T cell expression (CD5)
• bone marrow biopsy: not necessary for diagnosis but perfoirmed before therapy
• autoimmune anemia
• immunodeficiency as disease progresses

Question 18

Staging

Answer 18

1) Rai
0- lymphocytosis only
I - lymphadenopathy only
II - splenomegaly.hepatomegaly
III - anemia
IV - thrombocytopenia

2) BINET
A - no organ enlargement or up to 2 areas
B- 3-5 areas of organ enlargement
C - anemia/thrombocytopenia

Question 19

Therapy for CLL-

Answer 19

• treatment of early stage disease is not considered beneficial
• treatment indicated for anemia and orthrombocytopenia/ symptoms/ lymphadenopathy

Question 20

Treatment of underlying leuklemia in CLL

Answer 20

• chemotherapy: traditional use of alkylating agents in the elderly: chlorambucil, cyclophosphamide, corticosteroids
• increasing use of purine analogs in combination with other drugs = FCR
• radiotherapy
• allogeneic bone marrow transplant in rare young patient with progressive disease
• supportive care: IVIG for hypogammaglobulinemia, corticosteroids for AIHA