Table 4. Comparison of Treo PK parameters with the existing literature.
| N | Median age (yrs) | Conditions | Method | Regimen | Treo dose, g/m2 | AUC, µgxh/mL (mean ± SD) | CL, L/h (mean ± SD) | Cmax, µg/mL (mean ± SD) | Remarks | Reference |
|---|---|---|---|---|---|---|---|---|---|---|
| 8 10 |
40 51 |
AML, ALL, CML, T-NHL, MDS | RP-HPLC + RID | Treo:D -6 to -4 Cy:D -3 to -2 |
12 × 3 14 × 3 |
898 ± 104 1104 ± 173 |
— | 260 ± 35 322 ± 47 |
— | 27 |
| 1 5 1 |
14 | AML, AML/ALL, HL, ALD, WAS, SAA | RP-HPLC + RID | Treo | 10 × 3 12 × 3 14 × 3 |
735 1309 ± 921 1960 |
23.1 13.9 ± 7.1 3.6 |
271 420 ± 250 632 |
Linear increase in AUC with dose | 16 |
| 4 12 |
34 34 |
AML, ALL, MDS | RP-HPLC + RID | Treo:D -6 to -4 F-araA:D -6 to -2 |
12 × 3 14 × 3 |
1365 ± 293 1309 ± 262 |
9.2 ± 2.1 11.1 ± 2.2 |
461 ± 102 409 ± 84 |
— | 8 |
| 12 8 |
6.9 5.4 |
Hemoglobinopathies, Hematological malignancies, Immune deficiency | RP-HPLC + UV | Treo+F-ara/ATG/Alem/TAI | 14 × 3 | 1639 ± 237 | 6.85 | — | Patients’ serum samples were used. Treo AUC is the total of Treo + metabolite. | 19 |
| 1 8 7 |
7.5 | NBL, ALL, ES, DBA, SCN, ALD, ALL, CML, AML, WAS | LC-MS/MS | Treo | 10 × 3 12 × 3 14 × 3 |
1560 1478 ± 552 2400 ± 1267 |
4.68 5.41 ± 0.60 4.07 ± 1.58 |
791 544 ± 272 857 ± 582 |
— | 17 |
| 3 3 |
1 4 |
Pediatric oncology | RP-HPLC + UV | Treo + F-araA | 12 × 3 14 × 3 |
1486 ± 235 1412 ± 215 |
2.7 ± 1.0 9.6 ± 4.3 |
560 ± 89 525 ± 88 |
AUC is the total of Treo + metabolite. No difference in AUC with increasing dose | 47 |
| 87 | 9 | Thalassemia | RP-HPLC + RID | Treo:D -6 to -4 F-araA:D -6 to -2 |
14 × 3 | 1396 ± 715 | 15.9 + 14.8 | 401 + 208 | - | Present study |
AML, acute myeloid leukemia; ALL, acute lymphoblastic leukemia; CML, chronic myeloid leukemia; NHL, Non-Hodgkin’s lymphoma; MDS, myelodysplastic syndrome, HL, Hodgkin’s lymphoma, ALD, adrenoleukodystrophy; WAS, Wiskott–Aldrich syndrome; SAA, severe aplastic anemia; ES, Ewing’s sarcoma; DBA, Diamond–Blackfan anemia; SCN, severe congenital neutropenia; RP-HPLC, reverse phase high performance liquid chromatography; RID-refractive index detector; UV, ultraviolet detector; LC, MS/MS-liquid chromatography tandem mass spectrometry; Treo, Treosulfan; Cy, cyclophosphamide; F-araA, fludarabine; AUC, area under the time vs. plasma concentration curve; CL, clearance; Cmax, maximum concentration.