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Abstract
Background
There have recently been some reports suggesting that once-daily intravenous busulfan (IV Bu) as a conditioning regime for hematopoietic stem cell transplantation (HSCT) possibly reduces the toxicities without influencing the clinical outcome as compared with the traditional 4 times daily dosage schedule. We report here on the clinical outcome of once-daily IV Bu as a conditioning regime for HSCT in children with AML at a single treatment center.
Methods
We retrospectively analyzed nine AML children who received HSCT with using the once-daily IV Bu (110∼130 mg/m2 on 4 consecutive days) conditioning regimen at the Department of Pediatrics, Pusan National University Hospital from 2003 to 2007.
Results
The median age at HSCT was 8.25 years. As for the conditioning regimens, the HLA-matched sibling peripheral HSCT (N=4) was Flu/Bu, the CBT and unrelated BMT (N=4) was Flu/Bu/ATG and the autologous HSCT (N=1) was Bu/Cy. There was only one case of primary graft failure in an unrelated donor CBT recipient. The median time to neutrophil engraftment was 14 days and the median time to platelet engraftment was 19 days. The transplant-related toxicities were acceptable; there were no case with CNS toxicity and VOD was observed in two cases (1 mild case of VOD and 1 moderate case of VOD). Acute GVHD was noted in two cases (1 case of grade I and 1 case of IV). With a median follow up of 33 months, there were two cases of relapse and two cases of death.
Conclusion
Once-daily IV Bu as a conditioning regimen for HSCT in children with AML was well tolerated and convenient with relatively moderate toxicities, but additional studies are needed to determine the therapeutic efficacy and pharmacokinetics of once-daily IV Bu in children who are undergoing HSCT.
References
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Table 1.
Patient characteristics
Table 2.
The information of transplantation
Abbreviations: S, sibling; U, unrelated; A, autologous; PB, peripheral blood; CB, cord blood; BM, bone marrow; Flu, fludarabine 40mg/m2×4d; Bu, busulfan; Cy, cyclophosphamide 60mg/kg×2d; ATG, equine anti-thymocyte globulin 30mg/kg ×3d, ∗rabbit anti-thymocyte globulin 3mg/kg×3d; MTX, methotrexate; E, enoxaparin; P, prostaglandin E1; G, glutathione; V, vitamin E.
Table 3.
Transplant-related data of 9 patients received once-daily IV Bu
Table 4.
Transplant-related toxicities of 9 patients received once-daily IV Bu
Table 5.
GVHD and clinical outcomes of 9 patients received once-daily IV Bu
| No. | aGVHD | cGVHD | CMV | Follow-up (months) | Response at 100 days | Relapse | Outcome | Causes of death | |
|---|---|---|---|---|---|---|---|---|---|
| Antigenemia | Disease | ||||||||
| 1 | − | − | − | − | 20 | CR | − | Alive | − |
| 2 | − | − | − | − | 33 | CR | − | Alive | − |
| 2 3 | − | − | − | − | 33 39 | CR CR | − | Alive Alive | − |
| 4 | Grade I | − | − | − | 13 | CR | Yes∗ | Dead | PD |
| 4 5 | Grade I − | − | − | − | 13 65 | CR CR | Yes∗ Yes† | Dead Alive | PD − |
| 6 | NA | NA | − | − | 51 | CR | − | Alive | − |
| 7 | Grade IV | NA | − | ＋‡ | 3 | Dead | − | Dead | aGVHD |
| 8 | − | − | ＋ | − | 13 | CR | − | Alive | − |
| 9 | Auto | Auto | − | − | 37 | CR | − | Alive | − |
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