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IM13.1-19 | Common Malignancies and Oncology — PBL Case

CLINICAL SETTING

Dr Ananya Krishnan is the medical registrar on call at a tertiary teaching hospital in Chennai. It is 11 PM on a Monday. She is accompanying a final-year MBBS student, Rahul, who is on his general medicine posting. The casualty receives a call from the triage nurse: 'We have a 24-year-old man, Arun, referred from a peripheral clinic with a one-week history of fever and fatigue. He looks unwell.' Rahul glances at the referral note: haemoglobin 6.8 g/dL, WBC 68 × 10^9/L, platelets 22 × 10^9/L. There are no further details. Dr Ananya turns to Rahul: 'Before we see him, what do you want to do with these numbers?' Rahul opens his logbook.

Trigger 1: The Smear Arrives — A Diagnosis in the Dark

Arun is a 24-year-old undergraduate student. He has no significant past medical history and takes no regular medications. He developed fever, progressive fatigue, and pallor one week ago. He had a visit to a local clinic three days ago and was treated empirically for 'malaria' but did not improve. On examination: temperature 39.4°C, pulse 114/min, BP 96/62. He is pale, tachycardic, and has petechiae on both lower limbs. He has soft, non-tender bilateral cervical and axillary lymphadenopathy. There is no hepatosplenomegaly on initial examination. The emergency CBC confirms: Hb 6.4 g/dL, WBC 74 × 10^9/L, platelets 19 × 10^9/L. The peripheral blood smear report arrives: '85% blasts; uniform intermediate-sized cells with high N:C ratio, scant agranular cytoplasm, round nuclei with fine chromatin and 1–2 prominent nucleoli. MPO negative. PAS staining: coarse block-positivity.' Dr Ananya says: 'I want you to tell me exactly what diagnosis this smear is pointing to, and what the next three hours look like.'

DISCUSSION POINTS

  • Interpret the peripheral blood smear findings: what morphological and cytochemical features distinguish ALL from AML, and how do MPO-negative/PAS-positive blasts help narrow the diagnosis?
  • Arun has a platelet count of 19 × 10^9/L with petechiae. What are the specific haemorrhagic complications you must exclude in the next hour — and at what platelet threshold is the risk of spontaneous intracranial bleeding considered critical?
  • Formulate the emergency management priorities for a newly diagnosed acute leukaemia patient presenting with fever, severe anaemia, and thrombocytopenia in the first 3 hours.
Click to reveal Trigger 2: The Fever That Complicates Everything (discuss previous trigger first!)

Trigger 2: The Fever That Complicates Everything

Arun is admitted to the haematology unit. Blood cultures are drawn. His temperature climbs to 39.8°C by 2 AM. Repeat CBC in the morning shows neutrophils 0.3 × 10^9/L. The senior haematologist confirms acute lymphoblastic leukaemia (ALL), B-cell precursor type on flow cytometry. She plans to start induction chemotherapy (dexamethasone-vincristine-L-asparaginase protocol) but first asks the team to address the fever. Dr Ananya tells Rahul: 'He has febrile neutropenia. Walk me through the MASCC score for him.' Arun has no hypotension, is ambulatory, is 24 years old, has no COPD, was not on prior antifungal therapy, and has no dehydration. Meanwhile, the biochemistry results arrive: uric acid 9.8 mg/dL, potassium 5.9 mEq/L, phosphate 7.2 mg/dL, creatinine 1.6 mg/dL (rising from baseline 1.0). Calcium is 6.8 mg/dL.

DISCUSSION POINTS

  • Calculate Arun's MASCC score from the available data. Does this classify him as low-risk or high-risk febrile neutropenia? What is the management implication of this score in a resource-limited setting?
  • The biochemistry shows hyperuricaemia, hyperkalaemia, hyperphosphataemia, and hypocalcaemia with rising creatinine. What complication is developing, and is this spontaneous or treatment-related? What are the diagnostic criteria (Cairo-Bishop) and immediate management priorities?
  • Why is allopurinol (rather than rasburicase) typically used as first-line prevention for tumour lysis syndrome in resource-limited Indian settings, and in which specific situation would you choose rasburicase instead?
Click to reveal Trigger 3: Day 14: A New Problem (discuss previous trigger first!)

Trigger 3: Day 14: A New Problem

Arun completes the first two weeks of induction and achieves haematological improvement. On day 14, he develops a sudden high fever of 40.1°C. Blood cultures from day 1 grew Klebsiella pneumoniae (ESBL-producing) — he completed 10 days of meropenem. The new fever shows no obvious source. CT sinuses, chest, and abdomen show a 2 cm left lobe hepatic lesion with a 'halo sign' — a dense central core surrounded by a ground-glass halo. The haematologist examines Rahul: 'What organism causes a halo sign in an immunocompromised host, and what do you want to do next?' Arun's galactomannan antigen on serum is 2.8 (index >0.5 = positive). His amphotericin B is initiated. On the same day, his mother, who has been waiting outside, pulls Dr Ananya aside and says: 'Doctor, please don't tell him he has cancer — he is getting married in three months. He cannot bear this news. Please pretend it is a blood infection.'

DISCUSSION POINTS

  • Identify the pathogen responsible for the hepatic 'halo sign' and positive galactomannan in an ALL patient on chemotherapy. Name the antifungal class, specific agent, and dose used; and explain why this infection develops specifically during the post-induction phase.
  • Dr Ananya faces a direct request to withhold the cancer diagnosis from Arun. Analyse this request using the four principles of biomedical ethics (autonomy, beneficence, non-maleficence, justice). Under Indian law and ethical guidance, is the family's request legally binding on the treating physician?
  • How would you approach the conversation with Arun's family and then with Arun himself, taking into account the specific cultural and psychosocial dynamics of a young man with a newly diagnosed serious illness in India?
Click to reveal Trigger 4: Remission, Relapse, and a Goals-of-Care Conversation (discuss previous trigger first!)

Trigger 4: Remission, Relapse, and a Goals-of-Care Conversation

Arun achieves complete remission after induction and consolidation. He is enrolled in a maintenance therapy phase. Eighteen months later, he relapses — bone marrow biopsy shows 35% lymphoblasts. His ECOG performance status has declined to 3; he has lost 12 kg. Salvage chemotherapy is offered. Arun, who has now been fully informed of his diagnosis, attends a consultation with Dr Ananya and the palliative care team. He says: 'I know what relapse means. I have read about it. I do not want more chemotherapy that makes me too sick to be human. I want to spend whatever time I have at home, with my family, without being in hospital every week.' His parents are present and ask the team to 'try one more round.'

DISCUSSION POINTS

  • Arun has relapsed ALL with ECOG 3 and expresses a clear preference for no further chemotherapy. His parents request continued active treatment. How do you apply the principle of patient autonomy and shared decision-making in this conflict? At what point does continued aggressive chemotherapy shift from curative intent to futile treatment?
  • Design an evidence-based palliative care plan for Arun at this stage: address pain management (WHO analgesic ladder step, specific opioid, dose titration), management of the two most likely non-pain symptoms (dyspnoea and constipation), and psychological support elements.
  • Describe the common issues encountered in the final weeks of life for a young patient with haematological malignancy in India: what are the specific challenges of end-of-life care at home with a family that has not accepted the prognosis, and what communication and support strategies would you employ?

Group Task Assignments

  • Using the MASCC scoring system, calculate Arun's score from the clinical data provided in Trigger 2 and decide whether he should be managed as an inpatient or outpatient with oral antibiotics. Present your reasoning to the group.
  • Construct a step-by-step tumour lysis syndrome prevention protocol for a high-risk ALL patient — include the timing of allopurinol initiation, IV fluid rate, frequency of monitoring, electrolyte thresholds requiring intervention, and the decision rule for escalating to rasburicase.
  • Role-play the disclosure conversation between Dr Ananya and Arun's mother (requesting non-disclosure) followed by the disclosure conversation with Arun himself. Use the SPIKES communication framework: Setting, Perception, Invitation, Knowledge, Empathy, Strategy.
  • Review the goals-of-care conversation in Trigger 4. Draft an advance care plan document for Arun that captures his stated preferences (no further chemotherapy, home-based care), anticipates the decisions that may arise in the final weeks of life, and addresses his family's position.

Learning Issues

Research these questions and bring your findings to the discussion.

  1. [IM13.4] What are the clinical, morphological, and cytochemical features that distinguish ALL from AML, and what are the major subtypes of each based on the WHO 2022 classification?
  2. [IM13.4] What is tumour lysis syndrome? Define the Cairo-Bishop diagnostic criteria for laboratory TLS and clinical TLS; identify which malignancies carry the highest risk; and describe the prevention and treatment protocol.
  3. [IM13.4] What is febrile neutropenia? Define the diagnostic thresholds, describe the MASCC risk stratification score, and outline the empirical antibiotic management protocol for high-risk patients in an Indian tertiary hospital.
  4. [IM13.14] What is the standard induction chemotherapy protocol for ALL in adults, and what is the role and rationale for CNS prophylaxis with intrathecal chemotherapy?
  5. [IM13.18] What are the ethical and legal frameworks governing truth-telling and disclosure of a cancer diagnosis to a patient in India? Does a family member have the legal authority to withhold a diagnosis from a competent adult patient?
  6. [IM13.17] Apply the WHO three-step analgesic ladder to a patient with moderate-to-severe cancer pain: which opioid, at what starting dose, by which route, and at what frequency? What side effects must be anticipated and how are they prevented?
  7. [IM13.5] What are the common clinical problems encountered in the final days of life for a patient with haematological malignancy, and what are the key principles of end-of-life care in the Indian setting?