Haematology Module 1

A 45-year-old male was admitted to the hospital with a history of leukemia. He recently underwent CAR-T cell therapy, and within 24 hours post-infusion, he developed a high fever of 40°C, severe fatigue, and diffuse muscle pain.

His blood pressure dropped, and he began experiencing difficulty breathing.

Laboratory tests revealed markedly elevated levels of inflammatory markers such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and C-reactive protein (CRP).

The following intervention may be useful in this situation, except?

Bevacizumab

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Tocilizumab

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Corticosteroids

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Anakinra

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Etanercept

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Asciminib, a novel therapeutic agent, has been recently explored for its efficacy in newly diagnosed Chronic Myeloid Leukemia (CML).

Which of the following statements best describes the role and clinical impact of Asciminib in this patient population?

Asciminib functions as an allosteric inhibitor of the ABL1 kinase domain, targeting the myristoyl pocket, and has shown promise in overcoming resistance to other TKIs in newly diagnosed CML patients.

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Asciminib is a first-generation tyrosine kinase inhibitor (TKI) primarily used after resistance to imatinib has been established.

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Asciminib is a monoclonal antibody that targets the BCR-ABL fusion protein, showing significant efficacy in combination with chemotherapy in newly diagnosed CML.

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Asciminib acts as a second-generation TKI, similar in function to nilotinib and dasatinib, but with a more favorable safety profile in newly diagnosed CML patients.

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Asciminib is primarily used in the maintenance phase of CML treatment, following successful induction therapy with other TKIs.

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A 65-year-old man with a 5-year history of chronic lymphocytic leukemia (CLL) presents to your clinic with a 6-month history of recurrent sinus and chest infections. He has been treated with multiple courses of antibiotics, but the infections continue to recur. His CLL has been managed with a watch-and-wait approach, and his most recent complete blood count (CBC) shows a white blood cell count of 30,000/μL with 80% lymphocytes.

What is the most likely underlying cause of this patient’s recurrent infections, and what diagnostic test would you order to confirm this suspicion?

Hypogammaglobulinemia due to CLL-related immune dysfunction; order serum immunoglobulin levels

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Neutropenia due to bone marrow infiltration by CLL cells; order a bone marrow biopsy

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Respiratory tract colonization with a resistant organism; order a sputum culture

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Impaired cellular immunity due to CLL-related T-cell dysfunction; order a CD4 count

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Adverse effect of previous antibiotic therapy; order a stool culture for Clostridioides difficile

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Which one of the following cytogenetic abnormality has the best prognosis in Acute myelogenous leukemia?

translocation of chromosome 15 and 17

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deletion of chromosome 5q

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abnormality in chromosome 3q

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deletion of chromosome 7q

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abnormality in chromosome 11q and 23

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Clinical outcomes from acute myeloid leukemia is strongly related to which factor?

Age

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Gender

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Race

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Response to therapy

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Family history

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A 54-year-old man is diagnosed as having acute myeloid leukaemia. What is the single most important test in determining his prognosis?

Cytogenetics

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Gene-expression profiling

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White cell count at diagnosis

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Immunophenotyping

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Lactate dehydrogenase

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A 36 year old patient with acute promyelocytic leukemia (APML) develops symptoms of cough,dyspnea, fever, weight gain and edema 10 days after commencing ATRA. Further imaging reveals pleural and pericardial effusion and pulmonary infiltrates.Serial blood test shows progressive renal failure. Clinically the patient is in severe respiratory distress with severe hypoxemia.

What is the most appropriate next step in management?

Stop ATRA and give dexamethasone 10mg IV bd.

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Continue ATRA and give dexamethasone 10mg iv bd

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Stop ATRA and give frusemide infusion

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Stop ATRA and give high flow oxygen

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Commence non-invasive ventilation

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Which of the following chemotherapeutic agent is least likely to be beneficial in the treatment of AML?

All TransRetinoic Acid (ATRA)

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Cystoside Arabinoside(Ara-C)

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Idarobucin

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Daunorubicin

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Etoposide

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Which one of the following is not an indication for treatment in chronic lymphocytic leukaemia?

A lymphocyte count of 65 (10^9/L)

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Massive splenomegaly

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Platelet count of 70 (10^9/L)

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Night sweats

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Extreme fatigue

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A 65-year-old woman is reviewed. She is on the waiting list for a varicose vein operation but during the preoperative assessment was noted to have a raised lymphocyte count. She reports feeling well currently and clinical examination is normal. Her bloods were as follows:

Hb 118 g/l
Plt 184 (10⁹/l)
WBC 21.2 (10⁹/l)

There are no previous bloods to compare these results with. Following referral to haematology a diagnosis of chronic lymphocytic leukaemia was made. What is the most appropriate management?

No treatment is needed and the patient can proceed with the operation

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No treatment is needed but must cancel the operation

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Start Chlorambucil and cancel the operation

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Start fludarabine and proceed with operation but with quinolone prophylaxis

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Start Alemtuzumab but cancel the operation

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A 71-year-old woman with no significant past medical history is investigated for lymphocytosis. She has recently lost 7kg in weight and complains of lethargy. The following blood results are obtained:

Hemoglobin	98 g/l
Platelet	104 (10⁹/l)
White Blood Cells	70.3 (10⁹/l)
Blood film	Lymphocytosis. Smudge cells seen

Four months previously her white cell count was 30.5 (10⁹/l).

Cytogenetics: TP53 mutation is not present and IGHV is mutated.

What is the most appropriate management?

Venetoclax plus Obinutuzumab

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Fludarabine, Cyclophosphamide and Rituximab

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Chlorambucil

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No treatment and continue to monitor full blood count three monthly.

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Allogeneic stem cell transplantation

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A 77-year-old man with a history of chronic lymphocytic leukaemia is admitted to the Acute Medical Unit with pneumonia. This is his fourth admission for pneumonia in the past six months. Which one of the following factors is most likely to be responsible?

Hypogammaglobulinaemia

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Hypersplenism

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Decreased lymphocyte survival

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Transformation to high-grade lymphoma

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Immature lymphocytes

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Venetoclax has recently been proven to be useful in the treatment of which condition?

Chronic lymphocytic leukemia

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Relapsed multiple myeloma

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Acute promyeloid leukemia

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Myelodysplasia

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Refractory chronic myelocytic leukemia

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Ibrutinib has a role in the treatment of all the following types of malignancy except?

Myelodysplasia

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Chronic lymphocytic leukemia

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Mantle cell lymphoma

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Waldenstrom's macroglobulinemia

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Multiple myeloma

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A 52-year-old man with a history of anaemia and abdominal discomfort is diagnosed as having chronic myeloid leukaemia. He is commenced on imatinib.

What is the mechanism of action of imatinib?

Tyrosine kinase inhibitor

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EGF receptor antagonist

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Anti-CD52 monoclonal antibody

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Anti-CD23 monoclonal antibody

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p53 inhibitor

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A 45 year old man with Philadelphia chromosome positive acute lymphocytic leukemia(ALL) develops severe GI toxicity and fluid retention after using Imatinib.

What is the next appropriate step in management?

Change to Dasatinib.

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Continue with lower dose of Imatinib

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Stop imatinib and change to ARA-C

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Withhold imatinib and restart the following month.

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No change in treatment is required.

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The following are appropriate therapy for chronic phase of CML except?

Idarobucin

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Hydroxyurea

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Imatinib

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Interferon-gamma

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Bone marrow transplant

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A patient with myelodysplasia is at risk of transformation into which type of malignancy?

Acute Myeloid Leukemia

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Multiple Myeloma

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Chronic Myeloid Leukemia

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Chronic Lymphocytic Leukemia

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Burkitt's Lymphoma

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The following are poor prognostic factors for ALL except?

Minimal residual disease undetectable at day 33.

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WBC >50,000

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Age >35 yrs or <1

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Poor response to induction therapy

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Presence of Mixed Lineage Leukemia (MLL), bcr-abl gene.

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Which of the following treatment is most effective in physically fit patients with previously untreated chronic lymphocytic leukemia (CLL)?

Venetoclax + Rituximab

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Venetoclax + Obinutuzumab

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Obinutuzumab monotherapy

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Chemoimmunotherapy

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In the treatment of relapsed T-cell acute lymphoblastic leukemia (ALL) using base-edited CAR7 T cells, what primary mechanism is utilized to avoid graft-versus-host disease and enhance the safety profile of the therapy?

Base editing to inactivate genes encoding CD52 and CD7 receptors and the β chain of the αβ T-cell receptor

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Increasing the dose of immunosuppressive drugs post-infusion

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Selective targeting of cancer cells while sparing healthy T cells

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Use of traditional chemotherapy in conjunction with CAR T-cell therapy

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Enhancing the proliferation and longevity of CAR T cells in vivo

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The risk of tumour lysis syndrome is most likely related to:

reduction in glomerular filtration rate.

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advanced age

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High serum lactate dehydrogenase

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High white blood cell count

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High tumour volume

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What is the most common mechanism of acute renal failure in tumour lysis syndrome?

Hyperphosphataemia.

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Hyperuricemia

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Hypocalcemia

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Hyperkalaemia

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Hypomagnesemia

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A 15 year old male undergoing induction for acute lymphoblastic leukaemia is at risk of tumour lysis syndrome due to a high white cell count. Twelve hours following initial chemotherapy, the following investigations were obtained:

Calcium 2.0 mmol/L [2.15-2.65]
Phosphate 3.0 mmol/L [1.3-2.3]
Lactate Dehydrogenase (LDH) 9800 U/L [500-920]
Uric Acid 0.4 mmol/L [0.1-0.3]
Urinary pH 7.8
Urinary specific gravity 1018
Urinary nitrates +3

Which one of the following metabolites is most likely to precipitate within the renal tubules in the patient?

Calcium phosphate.

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Allantoin

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Hypoxanthine

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Sodium nitrate.

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Uric acid.

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A 15 year old man has a massive abdominal Burkitt lymphoma. What is the most useful treatment to prevent tumour lysis syndrome?

urate oxidase (Rasburicase)

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prednisolone

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mannitol.

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frusemide.

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allopurinol.

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Among the following type of lymphoproliferative disorder, which one carries the lowest risk for developing tumour lysis syndrome?

indolent non-Hodgkin's lymphoma (NHL)

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diffuse large B-cell lymphoma

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acute lymphoblastic leukemia

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acute myeloid leukemia

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Burkitt's lymphoma

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In patients with previously untreated CLL and coexisting conditions, which monoclonal antibody resulted in better outcomes when combined with chlorambucil?

Obinutuzumab

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Pembrolizumab

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Omalizumab

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Daratumumab

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Haematology Module 1

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