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]