Treosulfan-based conditioning regimens for allogeneic HSCT in children with acute lymphoblastic leukaemia

详细信息    查看全文

• 作者：Heidrun Boztug ; Marco Zecca ; Karl-Walter Sykora ; Paul Veys…
• 关键词：Treosulfan ; ALL ; Paediatrics ; Stem cell transplantation ; Toxicity
• 刊名：Annals of Hematology
• 出版年：2015
• 出版时间：February 2015
• 年：2015
• 卷：94
• 期：2
• 页码：297-306
• 全文大小：586 KB
• 参考文献：1. Peters C, Schrauder A, Schrappe M et al (2005) Allogeneic haematopoietic stem cell transplantation in children with acute lymphoblastic leukaemia: the BFM/IBFM/EBMT concepts. Bone Marrow Transplant 35(Suppl 1):S9-1 CrossRef
  2. Schrappe M, Reiter A, Zimmermann M et al (2000) Long-term results of four consecutive trials in childhood ALL performed by the ALL-BFM study group from 1981 to 1995. Berlin-Frankfurt-Munster. Leukemia 14:2205-222 CrossRef
  3. Pulsipher MA, Peters C, Pui CH (2011) High-risk pediatric acute lymphoblastic leukemia: to transplant or not to transplant? Biol Blood Marrow Transplant 17:S137-48 CrossRef
  4. Eckert C, Henze G, Seeger K et al (2013) Use of allogeneic hematopoietic stem-cell transplantation based on minimal residual disease response improves outcomes for children with relapsed acute lymphoblastic leukemia in the intermediate-risk group. J Clin Oncol 31:2736-742 CrossRef
  5. Schrauder A, von Stackelberg A, Schrappe M, Cornish J, Peters C (2008) Allogeneic hematopoietic SCT in children with all: current concepts of ongoing prospective SCT trials. Bone Marrow Transplant 41(Suppl 2):S71-4 CrossRef
  6. Balduzzi A, Valsecchi MG, Uderzo C et al (2005) Chemotherapy versus allogeneic transplantation for very-high-risk childhood acute lymphoblastic leukaemia in first complete remission: comparison by genetic randomisation in an international prospective study. Lancet 366:635-42 CrossRef
  7. Balduzzi A, Valsecchi MG, Silvestri D et al (2002) Transplant-related toxicity and mortality: an AIEOP prospective study in 636 pediatric patients transplanted for acute leukemia. Bone Marrow Transplant 29:93-00 CrossRef
  8. Linsenmeier C, Thoennessen D, Negretti L et al (2010) Total body irradiation (TBI) in pediatric patients. a single-center experience after 30?years of low-dose rate irradiation. Strahlenther Onkol 186:614-20 CrossRef
  9. Ricardi U, Filippi AR, Biasin E et al (2009) Late toxicity in children undergoing hematopoietic stem cell transplantation with TBI-containing conditioning regimens for hematological malignancies. Strahlenther Onkol 185(Suppl 2):17-0 CrossRef
  10. Bresters D, van Gils IC, Kollen WJ et al (2010) High burden of late effects after haematopoietic stem cell transplantation in childhood: a single-centre study. Bone Marrow Transplant 45:79-5 CrossRef
  11. Marks DI, Forman SJ, Blume KG et al (2006) A comparison of cyclophosphamide and total body irradiation with etoposide and total body irradiation as conditioning regimens for patients undergoing sibling allografting for acute lymphoblastic leukemia in first or second complete remission. Biol Blood Marrow Transplant 12:438-53 CrossRef
  12. Davies SM, Ramsay NK, Klein JP et al (2000) Comparison of preparative regimens in transplants for children with acute lymphoblastic leukemia. J Clin Oncol 18:340-47
  13. Baron F, Storb R, Storer BE et al (2006) Factors associated with outcomes in allogeneic hematopoietic cell transplantation with nonmyeloablative conditioning after failed myeloablative hematopoietic cell transplantation. J Clin Oncol 24:4150-157 CrossRef
  14. Pulsipher MA, Boucher KM, Wall D et al (2009) Reduced-intensity allogeneic transplantation in pediatric patients ineligible for myeloablative therapy: results of the pediatric blood and marrow transplant consortium study ONC0313. Blood 114:1429-436 CrossRef
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Hematology
  Oncology
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1432-0584

文摘

Standard myeloablative conditioning regimens for children with acute lymphoblastic leukaemia are based on total body irradiation (TBI). However, TBI causes profound short-term and long-term side effects, provoking the necessity for alternative regimens. Treosulfan combines a potent immunosuppressive and antileukaemic effect with myeloablative activity and low toxicity profile. We retrospectively studied toxicity and outcome of 71 paediatric patients with acute lymphoblastic leukaemia (ALL) undergoing haematopoietic stem cell transplantation (HSCT) following treosulfan-based conditioning aiming to identify risk factors for treatment failure and dose-depending outcome differences. Early regimen-related toxicity was low. No case of veno-occlusive disease was reported. There was no association of toxicity with age or number of HSCT. Event-free survival (EFS) of infants was significantly better compared to older children. Overall survival (OS) at 3?years was 51?% and not significantly influenced by number of HSCT (first HSCT 54?%, ≥second HSCT 44?%, p--.71). In multivariate analysis, OS and EFS were significantly worse for patients transplanted without complete remission (p--.04 and 0.004). Treatment-related mortality was low at 14?%. We conclude that treosulfan-based conditioning is a safe and efficacious approach for paediatric ALL.