Abstract
Myelodysplastic syndromes (MDS) are a heterogenous group of acquired hematopoietic stem cell disorders. Refractory cytopenia (RC) is the most common subtype of childhood MDS and hematopoietic stem cell transplantation (HSCT) is the only curative treatment. HSCT following a myeloablative preparative regimen is associated with a low probability of relapse and considerable transplant-related mortality. In the present European Working Groups of MDS pilot study, we investigated whether a reduced intensity conditioning regimen (RIC) is able to offer reduced toxicity without increased rates of graft failure or relapse. Nineteen children with RC were transplanted from an unrelated donor following RIC consisting of fludarabine, thiotepa and anti-thymocyte globulin. Three patients experienced graft failure. Neutrophil and platelet engraftment occurred at a median time of 23 and 30 days, respectively. Cumulative incidence of grade II–IV and grade III and IV acute graft-versus-host disease (GVHD) was 0.48 and 0.13, respectively; three patients developed extensive chronic GVHD. Although infections were the predominant complications, only one patient with extensive chronic GVHD died from infectious complications. Overall and event-free survival at 3 years were 0.84 and 0.74, respectively. In conclusion, our results were comparable to those of patients treated with myeloablative HSCT. Long-term follow-up is needed to demonstrate the expected reduction in long-term sequelae.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Hasle H, Niemeyer CM, Chessells JM, Baumann I, Bennett JM, Kerndrup G et al. A pediatric approach to the WHO classification of myelodysplastic and myeloproliferative diseases. Leukemia 2003; 17: 277–282.
Pui CH, Schrappe M, Ribeiro RC, Niemeyer CM . Childhood and adolescent lymphoid and myeloid leukemia. Hematology Am Soc Hematol Educ Program 2004, 118–145.
Kardos G, Baumann I, Passmore SJ, Locatelli F, Hasle H, Schultz KR et al. Refractory anemia in childhood: a retrospective analysis of 67 patients with particular reference to monosomy 7. Blood 2003; 102: 1997–2003.
Locatelli F, Zecca M, Zintl F, Nürnberger W, Ebell W, Niethammer D et al. Busulfan, cyclophosphamide and melphalan as preparative regimen to allogeneic stem cell transplantation in childhood MDS: results of the second interim analysis of the EBMT/EWOG-MDS study. Bone Marrow Transplant 2001; 27 (Suppl 1): S69–S70.
Yusuf U, Frangoul HA, Gooley TA, Woolfrey AE, Carpenter PA, Andrews RG et al. Allogeneic bone marrow transplantation in children with myelodysplastic syndrome or juvenile myelomonocytic leukemia: the Seattle experience. Bone Marrow Transplant 2004; 33: 805–814.
Storb R, Yu C, Wagner JL, Deeg HJ, Nash RA, Kiem HP et al. Stable mixed hematopoietic chimerism in DLA-identical littermate dogs given sublethal total body irradiation before and pharmacological immunosuppression after marrow transplantation. Blood 1997; 89: 3048–3054.
McSweeney PA, Niederwieser D, Shizuru JA, Sandmaier BM, Molina AJ, Maloney DG et al. Hematopoietic cell transplantation in older patients with hematologic malignancies: replacing high-dose cytotoxic therapy with graft-versus-tumor effects. Blood 2001; 97: 3390–3400.
Slavin S, Nagler A, Naparstek E, Kapelushnik Y, Aker M, Cividalli G et al. Nonmyeloablative stem cell transplantation and cell therapy as an alternative to conventional bone marrow transplantation with lethal cytoreduction for the treatment of malignant and nonmalignant hematologic diseases. Blood 1998; 91: 756–763.
Cantu-Rajnoldi A, Fenu S, Kerndrup G, van Wering ER, Niemeyer CM, Baumann I . Evaluation of dysplastic features in myelodysplastic syndromes: experience from the morphology group of the European Working Group of MDS in Childhood (EWOG-MDS). Ann Hematol 2005; 84: 429–433.
Bader P, Niemeyer C, Willasch A, Kreyenberg H, Strahm B, Kremens B et al. Children with myelodysplastic syndrome (MDS) and increasing mixed chimaerism after allogeneic stem cell transplantation have a poor outcome which can be improved by pre-emptive immunotherapy. Br J Haematol 2005; 128: 649–658.
Locatelli F, Nollke P, Zecca M, Korthof E, Lanino E, Peters C et al. Hematopoietic stem cell transplantation (HSCT) in children with juvenile myelomonocytic leukemia (JMML): results of the EWOG-MDS/EBMT trial. Blood 2005; 105: 410–419.
Storb R, Prentice RL, Sullivan KM, Shulman HM, Deeg HJ, Doney KC et al. Predictive factors in chronic graft-versus-host disease in patients with aplastic anemia treated by marrow transplantation from HLA-identical siblings. Ann Intern Med 1983; 98: 461–466.
Gooley TA, Leisenring W, Crowley J, Storer BE . Estimation of failure probabilities in the presence of competing risks: new representations of old estimators. Stat Med 1999; 18: 695–706.
Horn B, Baxter-Lowe LA, Englert L, McMillan A, Quinn M, Desantes K et al. Reduced intensity conditioning using intravenous busulfan, fludarabine and rabbit ATG for children with nonmalignant disorders and CML. Bone Marrow Transplant 2006; 37: 263–269.
Woodard P, Tong X, Richardson S, Srivastava DK, Horwitz EM, Benaim E et al. Etiology and outcome of graft failure in pediatric hematopoietic stem cell transplant recipients. J Pediatr Hematol Oncol 2003; 25: 955–959.
Del Toro G, Satwani P, Harrison L, Cheung YK, Brigid BM, George D et al. A pilot study of reduced intensity conditioning and allogeneic stem cell transplantation from unrelated cord blood and matched family donors in children and adolescent recipients. Bone Marrow Transplant 2004; 33: 613–622.
Jacobsohn DA, Duerst R, Tse W, Kletzel M . Reduced intensity haemopoietic stem-cell transplantation for treatment of non-malignant diseases in children. Lancet 2004; 364: 156–162.
Shenoy S, Grossman WJ, DiPersio J, Yu LC, Wilson D, Barnes YJ et al. A novel reduced-intensity stem cell transplant regimen for nonmalignant disorders. Bone Marrow Transplant 2005; 35: 345–352.
Cohen J, Gandhi M, Naik P, Cubitt D, Rao K, Thaker U et al. Increased incidence of EBV-related disease following paediatric stem cell transplantation with reduced-intensity conditioning. Br J Haematol 2005; 129: 229–239.
Bhatia S, Ramsay NK, Steinbuch M, Dusenbery KE, Shapiro RS, Weisdorf DJ et al. Malignant neoplasms following bone marrow transplantation. Blood 1996; 87: 3633–3639.
Curtis RE, Travis LB, Rowlings PA, Socie G, Kingma DW, Banks PM et al. Risk of lymphoproliferative disorders after bone marrow transplantation: a multi-institutional study. Blood 1999; 94: 2208–2216.
Author information
Authors and Affiliations
Consortia
Corresponding author
Rights and permissions
About this article
Cite this article
Strahm, B., Locatelli, F., Bader, P. et al. Reduced intensity conditioning in unrelated donor transplantation for refractory cytopenia in childhood. Bone Marrow Transplant 40, 329–333 (2007). https://doi.org/10.1038/sj.bmt.1705730
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.bmt.1705730
Keywords
This article is cited by
-
The effect of decitabine-combined minimally myelosuppressive regimen bridged allo-HSCT on the outcomes of pediatric MDS from 10 years’ experience of a single center
BMC Pediatrics (2022)
-
Thiotepa–fludarabine–treosulfan conditioning for 2nd allogeneic HCT from an alternative unrelated donor for patients with AML: a prospective multicenter phase II trial
Bone Marrow Transplantation (2022)
-
Improved outcomes of allogeneic hematopoietic stem cell transplantation including haploidentical transplantation for childhood myelodysplastic syndrome
Bone Marrow Transplantation (2020)
-
Conditioning regimen for allogeneic bone marrow transplantation in children with acquired bone marrow failure: fludarabine/melphalan vs. fludarabine/cyclophosphamide
Bone Marrow Transplantation (2020)
-
Outcome of allogeneic hematopoietic stem cell transplantation for hypoplastic myelodysplastic syndrome
International Journal of Hematology (2020)