Table 4.
Summary of studies assessing the use of treosulfan conditioning in children with malignant diseases.
| References | ALL (N) / study population (N) | Age range (years) | Conditioning regimen(s) | Treo dose | Tested outcome(s) | Toxicity (grade ≥III) |
|---|---|---|---|---|---|---|
| Wachowiak et al. (142); retrospective | 17/51 | 0.7–17 (median 8) | TreoVP16Cy (25%) TreoFluMel (18%) TreoCyMel (16%) TreoCy (18%) TreoFlu (18%) TreoMel (6%) |
30–42 g/m2 | Engraftment: 94% Graft failure: 6% CC: 90% RI: 22% DFS: myeloid malignancy: 71% lymphoid malignancies: 41% |
Day +100: Mucosal: 12% Renal: 2% |
| Beier et al. (143); retrospective | 16/109 | 0–18 | TreoFluThio (43%) TreoFlu (31%) TreoFluMel (15%) TreoMel (4%) TreoCy (2%) TreoMelCy (2%) TreoFluCy (1%) |
21–42 g/m2 | Engraftment: 100% OS in malignant group: 49% TRM: 11.9% |
Skin grade IV: 3.5% Pulmonary grade IV: 2% |
| Boztug et al. (144); retrospective | 71/193 | 0.4–18 (median 9.1) | TreoFluThio 33% TreoCy 25% TreoFlu 22% TreoFluMel 13% Other 7% |
33–45 g/m2 |
*3-year OS: 51% *3-year EFS: 39% *TRM: 14% |
*Stomatitis: 36% *Diarrhoea: 24% *Vomiting: 11% *Respiratory toxicity: 14% *Elevated bilirubin: 14% *Elevated SGOT: 27% *CNS toxicity: 4% *Peripheral neurotoxicity: 4% *VOD: 0% |
| Kalwak et al. (145); prospective, Phase II | 23/65 | 1–17 (median 12) | TreoFluThio | 30–42 g/m2 | Engraftment: 98.5% CC at Day +100: 92.2% *OS: 78.3% *RI: 26.1% *R/PFS: 69.6% NRM: 3.1% |
Mucositis oral: 43.1% Nausea and vomiting: 16.9% Infections and infestations: 30.8% Diarrhoea: 15.4% Skin and subcutaneous: 12.3% VOD: 0% |
| Peters et al. (34); prospective, Phase III | 93/93 | *4–18 | *TreoFluThio | *42 g/m2 |
*OS: 77% *EFS: 58% *CIR: 31% *TRM: 12% |
*Vomiting: 20% *Stomatitis: 56% *Infection: 65% *Peripheral neurotoxicity: 6% *HLH: 3% *PTLD 7% *Skin changes: 9% *Aspiration: 4% |
Data specific to the subgroup of patients with ALL.
ALL, acute lymphoblastic leukaemia; Bu, busulfan; CC, complete donor chimerism; DFS, disease-free survival; EFS, event-free survival; Flu, fludarabine; HLH, haemophagocytic lymphohistiocytosis; Mel, melphalan; NRM, non-relapse mortality; OS, overall survival; PTLD, post-transplant lymphoproliferative disorder; R/PFS, relapse/progression-free survival; RI, relapse incidence; SGOT, serum glutamic oxaloacetic transaminase; SOS, sinusoidal obstruction syndrome; Thio, thiotepa; Treo, treosulfan; TRM, treatment-related mortality; TRT, treatment-related toxicity; VOD, veno-occlusive disease; VP16, etoposide.