Child on treatment for T-ALL with dropping WBC counts

Hello,

Thank you for asking your query. The consult reply is from Dr. Saptharishi L G who is an expert in Paediatric Onco-Haematology.
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It pains me to know that your nephew is suffering from T cell ALL. Your description of the treatment that he is receiving seems to be at par with the standards of care worldwide. The Modified BFM 90 protocol is one of the most commonly used regimens. I do not think that we should contemplate on putting him on any alternate protocol at this point of time in his therapy.

The fall in counts occurs commonly after every chemotherapy cycle. Basically all the chemotherapeutic agents are powerful drugs that target rapidly dividing cells, hence cells of our blood, gut and mucosal surfaces also get attacked. These agents kill the cancerous cells but also suppress the bone marrow and hence produce a drop in counts typically 1-2 weeks after a chemotherapy cycle.This is an anticipated complication with chemotherapy. This is also the period in which these children acquire infections (fever) secondary to a weak immune system (attributable to low neutrophils - the cells that form the core of our immune response). This is known as febrile neutropenia. The most important count is the ABSOLUTE NEUTROPHIL COUNT. This is inversely proportional to the risk of infection.

Most of the times, the counts gradually recover within the next 5-10 days as the effect of the chemotherapeutic agents start coming down and the bone marrow partially recovers. In a small proportion of children, the neutropenia persists. This subgroup may benefit with the use of colony stimulating factors (GM-CSF/ G-CSF) like Filgrastim (Neupogen) and your nephew also seems to be receiving the same. There could be multiple causes of prolonged neutropenia including infections,etc. If neutropenia persists, it is better to visit your oncologist once more for a head-toe evaluation.

Regards

Dr. Saptharishi L G
MBBS, MD (Pediatrics), PGDCRL
Dept. of Pediatrics
Advanced Pediatrics Center
Post-Graduate Institute of Medical Education & Research
PGIMER, Chandigarh, India 160012

Thank you for your answer. Appreciate if you can respond to further specific questions we have.

We do understand that while in chemotherapy it is expected to be febrile neutropenia. However, right now he is not on intensive chemo. It is very mild dose and is on like that for a year now. These unstable neutrophil count has started only during last two months. So we have the following questions :

1st question : Now that we are reaching the end of maintenance therapy, how do we ascertain that his bone marrow is capable enough to produce good cells as required without help of neupogen.

2nd question : while in the maintenance therapy, the dose of mercaptopurine is same on all days, what causes the drop of neutrophils so drastically in some months, while in other months its stable and in acceptable limits.

3rd question : since this child is not having any external symptoms to determine low neutrophil count, how long do we need to continue with blood test every 10 days. This question is more from a point of view that , how do we determine when to keep the child away from school and his social circle.

Answer 1: There is no definitive way to assess if his bone marrow is 'ready'. That is usually apparent by the increase in counts, the ability of the bone marrow to recover. Sometimes, patients develop prolonged neutropenia despite completion of chemotherapy. It is difficult to predict whether a particular child would continue to have bone marrow suppression, and if yes, the duration of suppression. However most children recover quite early.

Answer 2: Mercaptopurine is metabolized in the body to multiple metabolites. TPMT genotype and concentrations of mercaptopurine metabolites measured in bone marrow leukemia cells could be different in different patients and in the same patient at different times. This could be responsible for your observation that despite the same dose of mercaptopurine, its effect on neutrophil counts is different at different times of the year.

Answer 3:
Frequent blood tests are important because doctors need to make sure that the amount of your child’s white blood cells (neutrophils or Polys) are not too low. If they are too low, then the chemotherapy is killing too many marrow cells, making your child neutropenic and at risk for developing an infection. If the amount of neutrophils is too high, then the therapy is not killing enough hidden leukemia cells. For this reason, making sure your child takes 6-mercaptopurine orally every day and methotrexate orally every week, without missing doses is essential to keep your child in remission and reduce the risk of relapse.

During maintenance, your child needs to maintain a healthy lifestyle. That is all that is needed. You need not ask him to avoid his social circle or schooling. You can encourage your child to eat nutritious food and to participate in daily exercise. Physical activity is very important to maintain good health and also minimize your child’s risk of becoming obese, which can be a long-term side-effect of the treatment. Generally, there are no restrictions on physical activity during maintenance chemotherapy (even if the central line is still in place). Kindly talk to your oncologist regarding specifics related to your child's health state and physical activity options.

Thank you