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Pediatric patients with hematological malignancies are commonly treated with busulfan- or fractionated total body irradiation (TBI)-based myeloablative conditioning regimens prior to allogenic hematopoietic stem cell transplantation (allo-HSCT). However, both these treatment options are associated with an increased risk of adverse events (AEs). Treosulfan-based conditioning prior to allo-HSCT has been shown to have myeloablative, immunosuppressive, and antineoplastic effects that are associated with a reduced risk of non-relapse mortality (NRM) in adult patients with AML and MDS. Therefore, Krzysztof Kalwak et al. published results of a phase II, non-randomized, prospective study that evaluated the safety and efficacy of treosulfan/fludarabine conditioning in children in Bone Marrow Transplantation.1
Clinical endpoint
Treatment and dosing
Table 1. Patient characteristics and transplant data by hematological malignancy1
ALL, acute lymphoblastic leukemia; AML, acute myeloid leukemia; ICH, International Council of Harmonization; JMML, juvenile myelomonocytic leukemias; MDS, myelodysplastic syndrome; N/A, not applicable |
|||||
|
Disease |
||||
---|---|---|---|---|---|
ALL (N = 23) |
AML (N = 29) |
MDS (N = 10) |
JMML (N = 3) |
Overall (N = 65) |
|
Age [years] |
|||||
Median |
12.0 |
8.0 |
14.0 |
2.0 |
11.0 |
ICH age group [n (%)] |
|||||
28 days to 23 months |
2 (8.7%) |
4 (13.8%) |
1 (10.0%) |
1 (33.3%) |
8 (12.3%) |
2–11 years |
7 (30.4%) |
14 (48.3%) |
2 (20.0%) |
2 (66.7%) |
25 (38.5%) |
12–17 years |
14 (60.9%) |
11 (37.9%) |
7 (70.0%) |
0 (0.0%) |
32 (49.2%) |
Number of HSCT [n (%)] |
|||||
First |
22 (95.7%) |
28 (96.6%) |
8 (80.0%) |
2 (66.7%) |
60 (92.3%) |
Second |
1 (4.3%) |
1 (3.4%) |
2 (20.0%) |
1 (33.3%) |
5 (7.7%) |
Treosulfan dose [n (%)] |
|||||
10 g/m2/day −6, −5, −4 |
1 (4.3%) |
3 (10.3%) |
0 (0.0%) |
1 (33.3%) |
5 (7.7%) |
12 g/m2/day −6, −5, −4 |
5 (21.7%) |
13 (44.8%) |
3 (30.0%) |
2 (66.7%) |
23 (35.4%) |
14 g/m2/day −6, −5, −4 |
17 (73.9%) |
13 (44.8%) |
7 (70.0%) |
0 (0.0%) |
37 (56.9%) |
Engraftment and chimerism
NRM and RI incidence
RFS/PFS
GvHD
GRFS and CRFS
OS
Safety
Pharmacokinetics
The treosulfan/fludarabine/thiotepa conditioning regimen with BSA-adapted dosing was deemed tolerable and efficacious in children with hematological malignancies. The cumulative incidences of OS and NRM compared well to other conditioning regimens. However, a limitation of this study is the small sample size of patients treated, particularly in the MDS and JMML subgroups. Therefore, the poor outcome shown for patients with JMML should be interpreted with caution. Based on recent clinical data, the European Commission has approved treosulfan in combination with fludarabine as part of conditioning treatment prior to allo-SCT in children older than 1 month with malignant diseases. This study provides further confirmation of the myeloablative potential of the treosulfan/fludarabine/thiotepa conditioning regimen, which induced a good rate of complete donor-type chimerism.
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