Treosulfan-based preparative regimens for allo-HSCT in childhood hematological malignancies: a retrospective study on behalf of the EBMT pediatric diseases working party.

Abstract

This retrospective analysis evaluated 51 children (0.7-17 years; median eight) with high-risk or advanced hematological malignancies, including 18 (35%) patients undergoing second/third hematopoietic SCT (allo-HSCT), not eligible for standard myeloablative regimens and transplanted from matched sibling (MSD) (n=24) or matched unrelated (MUD) (n=27) donors. Preparative regimens were based on treosulfan (TREO) i.v., a structural analog of BU, given at total dose of 30 g/m(2) (n=21) or 36-42 g/m(2) (n=30) in combination with, fludarabine, cyclophosphamide, melphalan and/or VP-16 according to diagnosis, and risk factors. Deaths due to early regimen-related toxicity (RRT) did not occur. Nonrelapse mortality was 8% at 1 year and 16% after 4 years. Myeloid engraftment was achieved in 94%, complete donor chimerism in 90% of patients. A 4-year incidence of relapse was 24%, and was significantly lower after MUD-HSCT (8%) than after MSD-HSCT (39%), but similar in children undergoing first (28%) or second/third HSCT (17%). A 4-year disease-free survival was 61%, but it was significantly better in myeloid (73%), than in lymphoid malignancies (41%). Thus, children with high-risk and advanced hematological malignancies and high-risk of life-threatening RRT can be transplanted effectively and safely using TREO-based regimens. Particularly favorable results were achieved in myeloid malignancies and in children undergoing second HSCT.

• Authors: J Wachowiak, K-W Sykora, J Cornish, A Chybicka, J R Kowalczyk, E Gorczyńska, M Choma, G Grund, C Peters, EBMT Pediatric Diseases Working Party
• Journal: Bone marrow transplantation (Bone Marrow Transplant) Vol. 46 Issue 12 Pg. 1510-8 (Dec 2011) ISSN: 1476-5365 [Electronic] England
• PMID: 21297673 (Publication Type: Clinical Trial, Journal Article, Multicenter Study)

Chemical References

• Antineoplastic Agents, Alkylating
• Etoposide
• Cyclophosphamide
• treosulfan
• Vidarabine
• Busulfan
• fludarabine
• Melphalan
• Carmustine

Topics

• Adolescent
• Antineoplastic Agents, Alkylating (administration & dosage)
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage)
• Busulfan (administration & dosage, analogs & derivatives)
• Carmustine (administration & dosage)
• Child
• Child, Preschool
• Cyclophosphamide (administration & dosage)
• Disease-Free Survival
• Etoposide (administration & dosage)
• Female
• Hematologic Neoplasms (mortality, therapy)
• Humans
• Infant
• Male
• Melphalan (administration & dosage)
• Retrospective Studies
• Survival Rate
• Transplantation Conditioning
• Transplantation, Homologous
• Vidarabine (administration & dosage, analogs & derivatives)