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Figure 1 shows the weight gain of five infants treated for acute lymphoblastic leukaemia (ALL) in relation to centile chart positions, who were treated at the Yorkshire Regional Centre for Paediatric Oncology and Haematology from 1996 until the present. Patients 1–4 were treated in accordance with the MRC UKALL Infant 1 chemotherapy protocol,1 and patient 5 in accordance with Interfant 99.2
The most striking aspect is that from diagnosis to end of intensive therapy (approximately week 40 of treatment), the first four patients, despite aggressive nutritional support, failed to thrive, with two requiring long term total parenteral nutrition (TPN) during maintenance therapy in order to rectify this. Patient 5, in contrast, thrived during treatment.
The infants treated on the MRC UKALL Infant 1 protocol all had grade III/IV gut toxicity following intensive therapy, resulting in the infants being highly catabolic; although some weight gain was achieved with TPN, it was difficult to sustain this increase with enteral feeding.
It became apparent that patients not fully weaned at diagnosis showed a severe delay in feeding skills, becoming orally defensive, resulting in a grossly inadequate solid intake throughout intensive treatment, which continued into maintenance therapy. The only patient to continue normal feeding development was patient 4, who was 36 weeks at diagnosis, and fully weaned.
Patient 5, like the others diagnosed under 30 weeks old, had delayed feeding skills, taking virtually no solids or feed orally. However, she did not show such severe gut toxicity. She was fed an amino acid based formula (Neocate, SHS International Ltd, UK) since induction therapy.
The failure of infants with ALL to thrive may be consequent on severe gut toxicity, length of treatment, and failure of weaning. The improved outcome of patient 5 may be the result of use of a different chemotherapy protocol, which included dexamethasome.
A second possibility is the early introduction of an amino acid based formula, which is a source of l-glutamine, an important nitrogen source for enterocytes, which plays a key role in maintaining mucosal cell integrity and gut barrier function.3,4 It may be that exposure to a continuous low dose of glutamine throughout intensive chemotherapy helped to reduce the severity of mucositis.