Acute Leukaemia and MDS

Question 1

Bone cells as an indicator of leuka

Answer 1

• If more than 1/5 bone cells are primitive and haven’t differentiated, this is indicative of acute leuka marrow emia

Question 2

Acute Leukaemia

Answer 2

• Result of accumulation of early myeloid (AML) or lymphoid (ALL) precursors in the bone marrow, blood and other tissues = early precursor increase = body doesn’t make blood cells properly.

Question 3

Acute Myeloid Leukaemia (AML)

Answer 3

• Anyone + any age (69)
• Undifferentiated, big nucleus of cells
• Immunological markers + cytogenetics also used to diagnose

Question 4

Clinical features of AML

Answer 4

• Features of bone marrow failure
• Anaemia - fatigue
• Infections
• Easy bruising + haemorrhage
• Organ infiltration by leukaemia cells
• Gum hypertrophy - common

Question 5

Prognosis for AML

Answer 5

• Good e.g. NPM1 mutation
• Bad e.g. FLT3 ITD (most common)
• Survival is poor because: High proportion of unfavourable cytogenetics – >3 mutations = more resistant to chemo

Question 6

Treatment of AML

Answer 6

• Intensive chemotherapy
• 3-4 cycles - 80% complete remission within 1 cycle
• For relapsed disease, further intensive chemo followed by BMT - otherwise Azacytidine

Question 7

Non-intensive treatment of AML

Answer 7

• Low dose chemo - Cytarabine - remissions in 8-18%

- Hypomethylating agents = Decitibine and Azacytidine - Change the proliferation of Leuk cells

Question 8

How to treat the AML mutations

Answer 8

• FLT3 inhibitors = Midostaurin, quizartinib

- IDH2 inhibitor = Enasidenib (AG221)

Question 9

Acute Lymphoblastic Leukaemia (ALL)

Answer 9

• Usually children (95% cure rate)

- Presents with fatigue, bruising, weight loss, hepatosplenomegaly due to infiltration of leuk into liver and spleen

Question 10

4 components of treatment of ALL

Answer 10

• Induction - mixture of steroids, IV, intrathecal chemo
• Intensification / CNS prophylaxis - Methotrexate penetrate blood brain barrier
• Consolidation - 20 weeks on
• Maintenance - 2 years on - IV given quarterly

Question 11

What procedure do high risk ALL patients undergo

Answer 11

Bone marrow transplant

Question 12

Treatment for relapse of ALL

Answer 12

• More intensive chemo
• Blinatumomab - easier to tolerate
• Inotuzumab, CAR-T-Cells, BMT

Question 13

How does Inotuzumab work

Answer 13

Inotuzumab antibody binds to CD22 with chemo drug attached to it and is rapidly metabolised into the cell - good way to get chemotherapy drug into cancerous cells.

Question 14

Chimeric antigen receptor (CAR) T cells mechanism

Answer 14

Take T cells out and genetically modify them to target leukemic cells

Question 15

Neutropenic sepsis =

Answer 15

• Life threatening complication of chemotherapy. Treat with broad spectrum IV antibiotics as soon as suspected

Question 16

Myelodysplasia (MDS)

Answer 16

• Several related disorders with common features;
• primitive cells between 5-20%.
• A heterogeneous group of clonal bone marrow stem cell disorders that result in ineffective haematopoiesis with reduced production of one or more of the peripheral blood cell lineages

Question 17

MDS clinical features

Answer 17

• Dysplasia
• Fatigue, infection, bleeding
• Increased risk of transformation to AML

Question 18

Diagnosis of MDS

Answer 18

• Nucleated RBC’s
• Neutrophils poorly differentiated
• Bilobed appearance with less granulation

Question 19

What is IPSS-R

Answer 19

• IPSS-R = used to stratify disease; depends on neutrophils, platelets, Hb, proportion of primitive cells in BM and chromosome.
• Risk scores varies from very low – very high = prognosis related

Question 20

Treatment of MDS

Answer 20

• Low risk = give EPO for anaemia
• High risk = treat as you would AML with intensive chemo and BMT
• If unfit/complex cytogenetics = azacytidine