Maintenance

The role of the maintenance phase is to destroy every leukemic cells remaining in the patient’s body that could have survived the induction and consolidation phases.

This two to three year low dose treatment is mainly done at home and induces much less sides effects than the previous stronger treatments.

The standard combination of drugs consists of daily 6-Mercaptopurine, weekly Methotrexate, and Prednisolone and Vincristine a dozen times a year.

6MP and MTX constitute the backbone of the ALL maintenance. For more than 50 years, the two molecules have both been used for the treatment of ALL at a daily and weekly dose of respectively 75mg/m² and 25mg/m². Since then and despite the need, no adapted formulations have been developed.

This lack of adequate 6MP / MTX pediatric formulation for ALL treatment. The main issue this project proposes to address is. Current MTX / 6MP formulations do not address the need of dosing flexibility as tablets only are available. In addition, the strengths currently available are too low (2.5 mg and 10 mg) for MTX and too high for 6-Mercaptopurine (50mg).

As results, children have to take many pills of MTX, and to divide 6MP pills to obtain the proper dose, which can result in poor compliance. It has been shown that poor compliance in the maintenance treatment phase of ALL has a negative impact on the disease free survival. The issue of compliance is particularly critical in adolescent where suboptimal adherence to maintenance therapy can affect their long term survival. Studies show that normalcy, egocentrism, concrete thinking and parental involvement may influence adolescent adherence to oral medication regimen.

Therefore, adult tablets are clearly not adapted for the treatment of ALL. The consequences of the absence of pædiatric formulation for the treatment of ALL are multiple and affect the entire chain from doctors to children. ·

• Doctors: Lack of flexibility for prescribers (inadequate dosage).
  
• Hospital Pharmacy: Lack of conformity with GMPs, additional workload for the medication preparation (capsule, suspensions, etc.). ·
• Parents: Lack of security, lack of standardization of administration, dangers related to drug manipulation, direct contact with cytostatic agent, sometimes inhalation of the crunched powder, especially for mother, and even sometimes pregnant women. ·
  
• Children: Lack of compliance (reflux, irregular intake and improper dosage with potential toxicity).