Neutropenia and neutrophil disorders: SAQ

Short-answer questions on neutropenia in children. The first prompt covers a febrile severely neutropenic three-year-old on chemotherapy, asking for the first-hour resuscitation and empiric antibiotic management, the severity grading and the mechanism-based classification, and the principles of marrow surveillance in the congenital syndromes. The second prompt covers an incidental chronic isolated neutropenia in a well infant of African ancestry, asking for the differential diagnosis between autoimmune neutropenia of infancy, benign ethnic neutropenia and the inherited disorders, the targeted investigations, and the counselling and safety-net.

Prompt

A previously well three-year-old boy receiving maintenance chemotherapy for acute lymphoblastic leukaemia is brought to the emergency department with a one-hour history of fever to 39.0 degrees Celsius. He looks pale and slightly mottled. His full blood count shows a haemoglobin of 92 g per litre, a platelet count of 110 times ten to the ninth per litre, and a white cell count of 1.2 times ten to the ninth per litre with 15 per cent neutrophils and no bands. The absolute neutrophil count is 0.18 times ten to the ninth per litre. A central venous line is in situ.

This child has febrile severe neutropenia complicating chemotherapy, and he is already showing mottling, so he must be treated as presumed bacteraemic and managed as an emergency in the first hour. The absolute neutrophil count of 0.18 times ten to the ninth per litre sits in the profound-severe band, and his fever of 39.0 degrees Celsius meets the febrile-neutropenia definition. The plan is resuscitation, cultures, and empiric anti-pseudomonal beta-lactam within the first hour, with escalation for his early shock. [1]

Question 1 (10 marks)

Outline your immediate management of this child in the first hour, define the severity of his neutropenia, and explain the mechanism-based classification that frames the broader topic. [1]

The immediate management is the febrile-neutropenia bundle. Assess airway, breathing and circulation; he is mottled, so recognise early shock, remembering that the signs of sepsis are blunted when the neutrophil count is near zero. Take blood cultures from every lumen of the central line and peripherally, send a urinalysis, and obtain a chest radiograph. Start empiric intravenous anti-pseudomonal monotherapy within the first hour: ceftazidime, piperacillin-tazobactam, cefepime or meropenem, weight-dosed by the local oncology protocol, with vancomycin added for suspected line or soft-tissue infection or haemodynamic instability. Resuscitate shock with isotonic crystalloid boluses of 10 mL per kilogram titrated to perfusion, and escalate to vasoactive support and paediatric intensive care if he does not respond. Maintain oral and perianal hygiene and avoid rectal instrumentation. [1]

His neutropenia is severe by definition. Neutropenia is graded by the absolute neutrophil count in three bands: mild 1.0 to 1.5, moderate 0.5 to 1.0, and severe under 0.5, all times ten to the ninth per litre, with infection risk climbing sharply in the severe band and counts under 0.1 considered profound. The absolute neutrophil count is the white cell count multiplied by the percentage of segmented neutrophils plus bands divided by 100. The mechanism-based classification localises the problem to one of four sites: production failure in the marrow (severe congenital neutropenia, marrow infiltration, chemotherapy), peripheral destruction (autoimmune and alloimmune), retention in the marrow (WHIM myelokathexis), or splenic sequestration. This child's mechanism is production failure from chemotherapy. [1]

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References5Show ledger

[1]Newburger PE, Dale DC Evaluation and management of patients with isolated neutropenia. Semin Hematol, 2013.PMID 23953336
[2]Welte K, Zeidler C, Dale DC Severe congenital neutropenia. Semin Hematol, 2006.PMID 16822461
[3]Dale DC, Cottle TE, Fier CJ, et al Severe chronic neutropenia: treatment and follow-up of patients in the Severe Chronic Neutropenia International Registry. Am J Hematol, 2003.PMID 12555210
[4]Rosenberg PS, Alter BP, Bolyard AA, et al The incidence of leukemia and mortality from sepsis in patients with severe congenital neutropenia receiving long-term G-CSF therapy. Blood, 2006.PMID 16497969
[11]Reich D, Nalls MA, Kao WH, et al Reduced neutrophil count in people of African descent is due to a regulatory variant in the Duffy antigen receptor for chemokines gene. PLoS Genet, 2009.PMID 19180233