UKALL 2003 - Delayed Intensifcation 1 and Drugs

This is the fourth phase of treatment and lasts 8 weeks (if all goes well – although as I indicated yesterday, Kezia has had a delay of a week). The phase won't start until your child's neutrophil count (ANC) is >0.75 (x 10⁹/L) and her platelet count is >75 (x 10⁹/L). .

The phase is divided into two parts: reinduction and then reconsolidation. In theory, there is a week's interval between the two but your child won't start the reconsolidation until the ANC and platelet counts are at the levels above.

The pattern of medication is very similar to that of the very first phase.

Let me talk a little bit about some of the medications.

Methotrexate (MTX): This can be administered intrathecally (IT - into the spine) or intravenously (IV - into the veins).

Every so often throughout the treatment your child will have a sample of spinal fluid taken (a lumber puncture). The fluid is analysed to check the leukaemia has not spread to the Central Nervous System (CNS). (If it does, with resultant risks to the brain, your child will be off-protocol and receive radiation therapy). Even when a child does not have CNS disease, methotrexate is administered as a prophylaxis. The lumber puncture and IT MTX are administered under general anaesthetic.

Methotrexate inhibits the production of folic acid which cells need to synthesize new DNA prior to splitting. Therefore the cell cannot split or replicate. It will therefore have a greater toxic effect on fast-splitting cells such as cancer cells but also hair and mouth cells.

During the third and fifth phases, Escalating Capizzi 1 and 2, the Methotrexate is administered into the veins (IV - intravenous). The dose is gradually increased by 50 mg/sq. m. throughout this stage from a starting point of 100 mg/sq. m. but is stopped at signs of toxicity – either low neutrophil counts (neutropenia), severe mucositis (sore/infected mouth) or liver/kidney dysfunction. In the case of a low neutrophil count, when it has recovered your child will restart at 80% of the last dose. In Escalating Capizzi 2 the starting dose is 50 mg/sq. m. below the final level attained in Escalating Capizzi 1 and then increased by 50 mg/sq. m. but again decrease the dose if toxicity occurs. In the case of mucositis the dosing alterations follow different rules.

In Kezia's case she only had two doses of IV methotrexate (week 15 and 19 - 100 mg/sq. m and 80 mg/sq. m) as her neutrophil counts were too low on the other occasions. I was initially concerned about this and consulted J. He reassured me that this was actually a good sign – the methotrexate was doing its job fine without the need for more and higher doses. She will start Escalating Capizzi 2 at 30 mg/sq. m.

I will continue with other drugs in forthcoming posts.