Abstract
We performed quantitative PCR-based serial chimerism testing of whole blood (WB) and CD3+ cells and retrospectively correlated the results of chimerism tests and the risk of graft loss in children undergoing transplant for non-malignant disorders. Twenty-four children were included in this study. All patients initially engrafted; subsequently, 12% lost the graft, 21% achieved complete donor chimerism and 67% had mixed chimerism (MC). Patients underwent delayed taper of cyclosporine (CsA) if they had MC. Overall survival was 87±7% (s.d.) at 5-years post transplant, and it was not affected by chimerism status. Both WB and CD3+ chimerism showed significant fluctuations with a peak in autologous cell signal occurring at a median of 7 months for WB and 2 months for CD3+ cells. Initial post transplant chimerism percentage in either WB or CD3+ lineage was not related to graft loss. Increasing MC to >30% host cells was seen in 33% of patients, and it was related to increased risk of graft loss, as previously published. However, 63% of children with increasing MC did not lose their graft. Additional studies of post transplant chimerism are required to improve our ability to accurately identify children at risk of graft loss following transplant for non-malignant disorders.
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
Baron F, Baker J, Storb R, Gooley T, Sandmaier B, Maris M et al. Kinetics of engraftment in patients with hematologic malignancies given allogeneic hematopoietic cell transplantation after nonmyeloablative conditioning. Blood 2004; 104: 2254–2262.
Baron F, Little MT, Storb R . Kinetics of engraftment following allogeneic hematopoietic cell transplantation with reduced-intensity nonmyeloablative conditioning. Blood Rev 2005; 19: 153–164.
Childs R, Clave E, Contentin N, Jayasekera D, Hensel N, Leitman S et al. Engraftment kinetics after nonmyeloablative allogeneic peripheral blood stem cell transplantation: full donor T-cell chimerism precedes alloimmune responses. Blood 1999; 94: 3234–3241.
Hoelle W, Beck JF, Dueckers G, Kreyenberg H, Lang P, Gruhn B et al. Clinical relevance of serial quantitative analysis of hematopoietic chimerism after allogeneic stem cell transplantation in children for severe aplastic anemia. Bone Marrow Transplant 2004; 33: 219–223.
Matthes-Martin S, Lion T, Haas OA, Frommlet F, Daxberger H, Konig M et al. Lineage-specific chimaerism after stem cell transplantation in children following reduced intensity conditioning: potential predictive value of NK cell chimaerism for late graft rejection. Leukemia 2003; 17: 1934–1942.
Hill R, Peterson FB, Storb R, Appelbaum F, Doney K, Dahlberg S et al. Mixed hematologic chimerism after allogeneic marrow transplantation for severe aplastic anemia is associated with higher risk of graft rejection and a lessened incidence of acute graft-versus-host disease. Blood 1986; 67: 811–816.
Jacobsohn D, Duerst R, Tse W, Kletzel M . Reduced intensity haematopoietic stem-cell transplantation for treatment of non-malignant diseases in children. Lancet 2004; 364: 156–162.
Horn B, Baxter-Lowe L-A, 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.
Ringden O, Remberger M, Svenberg P, Svahn B-M, Dahllof G, Gustafsson B et al. Fludarabine-based disease-specific conditioning or conventional myeloablative conditioning in hematopoietic stem cell transplantation for treatment of non-malignant diseases. Bone Marrow Transplant 2007; 39: 383–388.
Kikuta A, Ito M, Mochizuki K, Akaihata M, Nemoto K, Sano H et al. Nonmyeloablative stem cell transplantation for nonmalignant diseases in children with severe organ dysfunction. Bone Marrow Transplant 2006; 38: 665–669.
Willasch A, Hoelle W, Kreyenberg H, Niethammer D, Handgretinger R, Lang P et al. Outcome of allogeneic stem cell transplantation in children with non-malignant disease. Haematologica 2006; 91: 788–794.
Ortega M, Eacudero T, Caballin MR, Olive T, Ortega JJ, Coll MD . Follow-up of chimerism in children with hematological diseases after allogeneic hematopoietic progenitor cell transplants. Bone Marrow Transplant 1999; 24: 81–87.
Andreani M, Nesci S, Lucarelli G, Tonucci P, Rapa S, Angelucci E et al. Long-term survival of ex-thalassemic patients with persistent mixed chimerism after bone marrow transplantation. Bone Marrow Transplant 2000; 25: 401–404.
Andreani M, Manna M, Lucarelli G, Tonucci P, Agostinelli F, Ripalti M et al. Persistence of mixed chimerism in patients transplanted for the treatment of thalassemia. Blood 1996; 87: 3494–3499.
Nesci S, Manna M, Pattorini P, Graziosi G, Lucarelli G . Mixed chimerism after bone marrow transplantation. Bone Marrow Transplant 1992; 10: 143–146.
Walters MC, Patience M, Leisenring W, Rogers ZR, Aquino VM, Buchanan GR et al. Stable mixed hematopoietic chimerism after bone marrow transplantation for sickle cell anemia. Biol Blood Marrow Transplant 2001; 7: 665–673.
Vermylen C, Cornu G, Ferster A, Brichard B, Ninane J, Ferrant A et al. Haematopoietic stem cell transplantation for sickle cell anemia: the first 50 patients transplanted in Belgium. Bone Marrow Transplant 1998; 22: 1–6.
Przepiorka D, Wiesdorf D, Martini P, Klingemann HG, Beatty P, Hows J et al. 1994 consensus conference on acute GVHD grading. Bone Marrow Transplant 1995; 15: 825–828.
Shulman HM, Sullivan KM, Weiden PL, McDonald GB, Striker GE, Sale GE et al. Chronic graft-versus-host syndrome in man: long-term clinicopathologic study of 20 Seattle patients. Am J Med 1980; 69: 204–217.
Scharf S, Smith A, Hansen J, McFarland C, Erlich H . Quantitative determination of bone marrow transplant engraftment using fluorescent polymerase chain reaction primers for human identity markers. Blood 1995; 85: 1954–1963.
Iannone R, Casella JF, Fuchs EJ, Chen AR, Jones RJ, Woolfrey A et al. Results of minimally toxic nonmyeloablative transplantation in patients with sickle cell anemia and beta-thalassemia. Biol Blood Marrow Transplant 2003; 9: 519–528.
Burroughs LM, Strob R, Leisenring WM, Pulsipher MA, Loken MR, Torgerson TR et al. Intensive postgrafting immune suppresssion combined with nonmyeloablative conditioning for transplantation of HLA-identical hematopoietic cell grafts: results of a pilot study for treatment of primary immunodeficiency disorders. Bone Marrow Transplant 2007; 40: 633–642.
Ozsahin H, Cavazzana-Calvo M, Notarangelo LD, Schulz A, Thrasher AJ, Mazzolari E et al. Long-term outcome following hematopoietic stem cell transplantation in Wiskott–Aldrich syndrome: collaborative study of the European Society for Immunodeficiencies and the European Group for Blood and Marrow Transplantation. Blood 2008; 111: 439–445.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Ozyurek, E., Cowan, M., Koerper, M. et al. Increasing mixed chimerism and the risk of graft loss in children undergoing allogeneic hematopoietic stem cell transplantation for non-malignant disorders. Bone Marrow Transplant 42, 83–91 (2008). https://doi.org/10.1038/bmt.2008.89
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/bmt.2008.89
Keywords
This article is cited by
-
Long-term outcomes of fludarabine, melphalan and antithymocyte globulin as reduced-intensity conditioning regimen for allogeneic hematopoietic stem cell transplantation in children with primary immunodeficiency disorders: a prospective single center study
Bone Marrow Transplantation (2016)
-
Transplantation tolerance
Pediatric Nephrology (2014)
-
A combination of fludarabine, half-dose cyclophosphamide, and anti-thymocyte globulin is an effective conditioning regimen before allogeneic stem cell transplantation for aplastic anemia
International Journal of Hematology (2014)
-
Haploidentical related-donor hematopoietic cell transplantation in children using megadoses of CliniMACs-selected CD34+ cells and a fixed CD3+ dose
Bone Marrow Transplantation (2013)
-
Reduced-intensity conditioning hematopoietic SCT for pediatric patients with LAD-1: clinical efficacy and importance of chimerism
Bone Marrow Transplantation (2012)