Leukaemia in children: SAQ

This boy has a trilineage cytopenia with circulating lymphoblasts, organomegaly and lymphadenopathy, which is the classic presentation of acute lymphoblastic leukaemia. The combination of pallor, bruising and fever with blasts is a medical emergency, and the task is to resuscitate the unstable elements first, to confirm the diagnosis rapidly, and to move to risk-stratified therapy in a specialist centre. [1]

Question 1 (10 marks)

Outline your immediate assessment, the stabilisation, and the urgent diagnostic pathway for this four-year-old boy. [7]

A full-mark answer covers the recognition of the emergency, the resuscitation by the three legs of transfusion, tumour lysis prophylaxis and empiric antibiotics, and the bone marrow diagnostic pathway with the ancillary studies that deliver the named diagnosis and the risk group. [1]

Recognition and the first priority (1 mark). The combination of pallor, bruising and fever with circulating blasts is acute leukaemia until proven otherwise, and the first priority is the resuscitation of the unstable elements, the anaemia, the bleeding risk, the neutropenic fever, and the tumour lysis risk. [9]

Resuscitation by transfusion (3 marks). Red cells are transfused for the symptomatic anaemia, given slowly in the chronically severely anaemic child to avoid the circulatory overload, and all the cellular products are irradiated and leucodepleted to prevent the transfusion-associated graft-versus-host disease. Platelets are transfused prophylactically under ten times ten to the nine per litre in the stable child and under twenty in the febrile or the bleeding child, at a higher threshold for the active bleeding or before a procedure. [7]

Tumour lysis prophylaxis (3 marks). A bulky or high-turnover tumour carries the risk of the tumour lysis syndrome, which is prevented before the first dose of chemotherapy. Hyperhydration with an isotonic fluid without potassium, started early and run to maintain a urine output above two millilitres per kilogram per hour, is the foundation. Rasburicase, a recombinant urate oxidase, is given to the high-risk child to break down the urate already formed, and is far more effective than the allopurinol, which only blocks the new urate formation. Rasburicase is contraindicated in the glucose-6-phosphate dehydrogenase deficiency because it causes the haemolysis and the methaemoglobinaemia. The potassium, phosphate, calcium, creatinine and urate are measured every four to six hours. [3]

Diagnostic pathway (3 marks). Blood cultures are drawn and an empiric antipseudomonal beta-lactam such as the piperacillin-tazobactam is given within one hour for the febrile neutropenia. The bone marrow aspirate and the trephine biopsy are performed together at the posterior iliac crest once the child is stable, with the aspirate providing the cells for the morphology, the flow cytometry to define the lymphoid lineage, and the cytogenetics and the molecular panel that drive the risk stratification. The diagnosis rests on the integration of the morphology, the immunophenotype and the genetics, and the lumbar puncture with the intrathecal therapy is performed at the specialist centre. [1]

Question 2 (10 marks)

Discuss the risk stratification and the risk-adapted definitive therapy once the diagnosis of B-cell precursor acute lymphoblastic leukaemia is confirmed, and contrast it briefly with the therapy of acute myeloid leukaemia. [1]

A full-mark answer reproduces the standard-risk criteria, the cytogenetic modifiers, the role of the minimal residual disease, and the treatment phases, and it contrasts the shorter, more intensive AML course. [5]

Risk stratification (3 marks). The standard risk, by the National Cancer Institute criteria, is the age of one to under ten years with an initial white cell count under fifty times ten to the nine per litre, and this boy at four years with a count of thirty-five is the standard risk by the clinical criteria. The favourable cytogenetics are the ETV6-RUNX1 fusion and the high hyperdiploidy, and the unfavourable are the KMT2A rearrangement, the hypodiploidy, the iAMP21 and the BCR-ABL1. The minimal residual disease at the end of the induction is the key determinant of the risk group and the intensity that follows. [5]

The definitive therapy (4 marks). The treatment is the risk-stratified multi-agent chemotherapy delivered over two to three years through the phases of the remission induction, the consolidation, the interim maintenance, the delayed intensification and the maintenance, with the central nervous system-directed therapy woven through every phase. The induction backbone includes the vincristine, a glucocorticoid of the dexamethasone or the prednisone, the asparaginase and the anthracycline, with the intrathecal therapy from day one, and it achieves the remission in over ninety-five percent within four weeks. The maintenance is the daily mercaptopurine and the weekly methotrexate for two years in the girl and three in the boy. [1][5]

Contrast with AML (2 marks). The acute myeloid leukaemia is treated with the intensive blocks of the anthracycline and the cytarabine over a much shorter course of roughly six months, it carries a lower survival of about sixty-five to seventy percent, and the stem cell transplant is reserved for the high-risk cytogenetics and the refractory disease. The acute promyelocytic leukaemia is the exception, treated with the all-trans retinoic acid and the arsenic trioxide, started on suspicion because of the coagulopathy. [7]

Synthesis (1 mark). The fellow who can hold the risk stratification, the treatment phases and the minimal residual disease together, and who can contrast the lymphoblastic and the myeloid pathways, has the framework that organises the whole topic of the childhood leukaemia. [5]