Monitors mercaptopurine levels in children with leukemia during maintenance treatment

AI summary

From the trial's eligibility criteria. Machine-read from the registry text on this page, so it can be wrong. The registry text below and the trial team decide who can take part.

The trial is looking for children and teenagers newly diagnosed with acute lymphoblastic leukemia (ALL).

Age

Younger than 18 years at diagnosis (maximum age 18 years).

Sex

All sexes can join.

Disease stage

Newly diagnosed acute lymphoblastic leukemia (ALL).

The registry criteria, word for word

What the trial wants to find out

Acute lymphoblastic leukemia (ALL) is the most common hematological malignancy in children (<18 years). The success of pediatric ALL therapy is remarkable but important challenges still need to be faced, including cure rates in specific patients' subsets (e.g.: adolescents and relapsed patients), and short- and long-term chemotherapy-related toxicities. The therapeutic scheme of the Associazione Italiana Emato-oncologia pediatrica (AIEOP) ALL protocols consists in a more intensive and toxic earlier phase (to induce and consolidate remission, about 6 months), followed by a prolonged period of immunosuppression (achieved by self- or parent-administered daily mercaptopurine (MP) and weekly methotrexate (MTX) per os). It is now well established that the length of the maintenance phase (up to 24 months after diagnosis) is as necessary as the early remission induction for sustained event-free survival (EFS). Both MP and MTX can lead to potentially serious complications, including potentially life-threatening myelosuppression and infections. To exert its therapeutic effect, MP requires an intracellular enzymatic conversion into active thionucleotides (TGN) and is thus susceptible to intra- and inter-individual variations in efficacy and toxicity. Patients carrying variants in TPMT and NUTD15 genes are at risk of adverse effects when treated with standard MP doses: these patients are identifiable by pre-emptive genotyping. Recent studies demonstrated that an adequate and constant MP exposure during maintenance is associated with higher therapeutic success. Prescribed MP doses are often changed by physicians to target a white blood cell count (WBC) range of 2.0-3.0 × 109/L during maintenance. In the AIEOP ALL 2009 protocol, patients with lower mean TGN exposure during maintenance showed a trend towards a higher risk of relapse compared to others. Similarly, patients with higher intra-individual variability in TGN over time showed a trend towards a worse outcome. Daily compliance to prescribed MP over time is a challenging issue for patients and may result in less effective therapy. The high intra-individual variability in exposure due to the frequent dose adjustments and the potential lack of patients' adherence to oral MP therapy over time might contribute to the risk of relapse. The aim of this study is to assess through therapeutic drug monitoring of MP if patients' exposure during maintenance is adequate and constant.