T7-L9 Acute Leukaemia and MDS

Question 1

For Acute Myeloid Leukaemia, give:

(a) Epidemiology
(b) Clinical features
(c) Diagnosis

Answer 1

(a) Median age of 69 years old. Survival rates tend to worsen with age.
(b) Anaemia, Infections and easy bruising and haemorrhage (due to thrombocytopenia). There can be infiltration of cancer cells into organs such as spleen, liver, meninges, testes and skin.
(c) Morphology, Immunological markers and Cytogenetics. On FBC, may see anaemia, a low or high (primitive) WCC and Thrombocytopenia.

Question 2

Why do some patients not respond as well to chemotherapy with AML?

Answer 2

• Age - increase age comes with worsened prognosis with treatment.
• Cytogenetic changes - Some changes show better response to treatment that other.
• Molecular features - NPM1 (a marker that shows a better prognosis) and FLT3-ITD (poor risk marker)
• Extramedullary disease (myeloma cells form tumours outside the bone marrow in the soft tissues or organs of the body) - patients with such tend not worse.
• Disease that doesn’t respond to the first cycle to treatment tend not to do as well
• Higher levels of comorbidity
• Multidrug resistance
• Preexisting haem disorders

Question 3

What are complications of intensive therapy?

Answer 3

• Alopecia
• Nausea and vomiting
• Potential loss of fertility
• Fatigue
• Weight loss
• Altered taste sensation
• Infection
• Mortality

Question 4

When does AML tend to relapse? After how long in remission is a patient considered to be cured?

Answer 4

• Typically relapses in AML occur within 18 months of intensive chemotherapy finishing
• At 4 years post chemo likely cured

Question 5

By how long does low does chemotherapy improve survival?

Answer 5

Can get complete remission in 8-18% of patients and can prolong survival (for around 6 months) but this comes with increased fatigue, infections etc. Without chemotherapy but instead supportive agents, the average survival is 3 months.

Question 6

What is Azacytidine?

Answer 6

Hypomethylating agent. It is well tolerated but is an irritant under the skin (it is given as a s/c injection). It is generally use in those that cannot tolerate chemo. It increases survival more than low dose chemotherapy.

Question 7

What is Venetoclax?

Answer 7

Venclexta (venetoclax) is a type of targeted treatment rather than chemotherapy.

Venetoclax is a type of targeted treatment rather thanchemotherapy. It is a B-cell lymphoma 2 (BCL-2) selective inhibitor. The BCL2 gene is a regulator that regulates apoptosis. Combination treatment can further increase survival. The combination of Venetoclax and Aza is well tolerated and better for treatment of AML in the elderly.

Question 8

What is the clinical presentation of Acute Lymphoblastic Leukaemia?

Answer 8

It is usually picked up at routine appointments. Change that can be seem include:

• Fatigue
• Bruising/bleeding
• Weight loss
• Night sweats
• Hepatosplenomegaly
• Lymphadenopathy
• Mediastinal mass

Question 9

What is the epidemiology of Acute Lymphoblastic Leukaemia?

Answer 9

ALL is the commonest cancer in children. Children with ALL tends to have good survival. In adults there are two peaks of activity - young adults 18-24- and older adults - over 60s. The older we get the harder it is it treat.

Question 10

When does relapse in ALL tend to occur?

Answer 10

Relapse tends to occur within the first 18 months. Relapse with ALL used to have poor survival (4 months). This is improved.

Question 11

What are options for relapsed disease?

Answer 11

• Further intensive chemotherapy
• Blinatumomab - It is an antibody that brings the T cell in direct contact with the tumour cell. It is generally a bridging drug. It gets people into remission so that they can get a transplant using a much better drug.
• Inotuzumab - This delivers chemo drugs into the cancer cells so it can kill the cancer from within. It is a monoclonal antibody that binds to CD22-expressing tumour cells to induce cell cycle arrest and apoptotic cell death.
• CAR-T cells
• BMT – sib/MUD/Cord/Haplo

Question 12

What is neutropenic sepsis?

Answer 12

Neutropenic sepsis is a life-threatening reaction to an infection, which can happen in patients with neutropenia. Symptoms include fever, hypotension and organ impairment. It is treated with broad spectrum IV antibodies as soon as it is suspected.

Question 13

What is Myelodysplastic syndrome (MDS)?

Answer 13

It is a bone marrow failure syndrome. We tend to see it in older patients. It covers a broad range of syndromes - from mild to those in pre-Leukaemia. The bone marrow gets rid of the blood cells that have not been made well. This leads to anaemia, thrombocytopenia. If severe it can lead to Leukaemia.

Question 14

What are features of MDS?

Answer 14

• Anaemia
• Dysplasia
• Ineffective haematopoiesis
• Cytopenias
• Increased risk of transformation to AML