Target Busulfan Exposure in Children With HSCT in China

Objectives To evaluate the correlation between BU exposure and post-transplant clinical results (efficacy and safety) to establish the optimal BU treatment window for myeloablative conditioning in Chinese pediatrics, provide theoretical basis and the new strategy for BU individualized dosage, further optimize transplant treatment and reduce drug-related toxicity.

Population 500 participants of any sex between the age of 0.1 and 18 years. Patients receiving the BU-based myeloablative conditioning before transplantation.

Endpoint primary To establish BU pop-PK model and analyze the association between BU AUC and event-free survival (EFS)or overall survival (OS) after transplantation in Chinese pediatrics.

Secondary The investigators are also interested in transplantation-related mortality (TRM), acute toxicity and chronic GvHD.

Objectives To evaluate the influence factors of BU metabolism in children and the correlation between BU exposure and post-transplant clinical results (efficacy and safety) to establish the optimal BU treatment window for myeloablative conditioning in Chinese pediatrics, provide theoretical basis and the new strategy for BU individualized dosage, further optimize transplant treatment and reduce drug-related toxicity.

Endpoint primary The main study endpoints are event-free survival (EFS) and overall survival (OS). EFS is calculated from the time of transplant until death, relapse of disease, or graft failure (defined as non-engraftment or rejection), whichever occurred first. OS is the time between transplantation and death of any cause. All surviving patients are censored at day of last contact. Duration of follow-up is the time from transplant to the last assessment for surviving patients or death.

Secondary The investigators are also interested in transplantation-related mortality (TRM), acute toxicity and chronic GvHD. TRM is defined as death unrelated to underlying disease. Acute toxicities are defined as VOD (diagnosed according to modified Seattle criteria), acute GvHD grade II-IV (diagnosed and graded according to Mount Sinai Acute GvHD International Consortium (MAGIC) criteria, oral mucositis (grade II-IV) and hemorrhagic cystitis (grade II-IV). Two of the most commonly utilised scales for oral mucositis are the WHO and NCI-CTCAE scales. Chronic GvHD should be graded as mild, moderate or severe according to the National Institutes of Health (NIH) consensus criteria.

Eligibility Criteria:
Inclusion Criteria:

1. The subjects or their legal guardians voluntarily sign the informed consent, and can complete the study in accordance with the requirements of the program;
2. No age or gender restriction;
3. Patients with blood disease confirmed by histopathology or cytology;
4. BU-based regimen will be adopted. The BU administration regimen was four times a day (Q6h), continuous intravenous infusion for 2 hours, 3 or 4 days in a row.

Exclusion Criteria:

1. Patients with difficulty in vein blood sampling (if there is a needle, blood history);
2. BU TDM was not performed during the treatment;
3. Subjects who are considered unfit to participate in the trail by the investigator.