Every year around 70 children affected by cancer or life-threatening genetic diseases undergo haematopoietic cell transplantation (HCT) within the Blood and Marrow Transplant (BMT) unit at Great Ormond Street Hospital (GOSH).

One of the main goals of the BMT unit over the last decade has been to reduce the morbidity and mortality related to HCT, and the group has become a world-leader in pioneering less toxic transplants.

Fixed high doses of chemotherapy drugs are generally used to prepare children for HCT but several studies have shown a correlation between the concentration of these drugs achieved in the patient's blood, and the success or failure of the HCT procedure.

Recently a new drug, Treosulfan, has become available for use in patients undergoing HCT, and GOSH has pioneered its introduction in children undergoing HCT. With promising early results, Treosulfan has become the pre-HCT drug of choice, however, very little is currently known about how the drug is metabolised and cleared from the body, particularly in children.

The investigators therefore plan to investigate the pharmacokinetic (PK) profile of Treosulfan in children undergoing HCT at GOSH and define which parameters affect its metabolism and clearance, and what blood levels are associated with a favourable outcome (graft take without toxicity) or a poor result (graft rejection and/or toxicity).

Inclusion Criteria:

1. age ≥ 28 days and ≤ 18 years old;
2. Karnofsky Performance Status ≥ 50 or Lansky Performance Status ≥ 30;
3. provide signed, written informed consent from parent or guardian;
4. be able to comply with study procedures and follow-up examinations;
5. have adequate organ function (as indicated by Table 1, page 27), within 14 days prior enrollment;
6. negative pregnancy test in post-pubertal female patients.

Exclusion Criteria:

1. patients aged < 28 days and > 18 years old;
2. patients with compromised organ function*;
3. patients with any other severe concurrent disease, which, in the judgment of the Investigator, would make the patient inappropriate for entry into this study;
4. known hypersensitivity to Treosulfan or Fludarabine;
5. pregnancy/lactation.

Children affected by malignant or non-malignant diseases with an indication to allogeneic HSCT.