Rapid donor T-cell engraftment increases the risk of chronic graft-versus-host disease following salvage allogeneic peripheral blood hematopoietic cell transplantation for bone marrow failure syndromes

Jeremy Mark Pantin, Xin Tian, Avni A. Shah, Roger Kurlander, Catalina Ramos, Lisa Cook, Hahn Khuu, David Stroncek, Susan Leitman, John Barrett, Theresa Donohue, Neal S. Young, Nancy Geller, Richard W. Childs

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Abstract

The risk of graft-rejection after allogeneic hematopoietic cell transplantation using conventional cyclophosphamide-based conditioning is increased in patients with bone marrow failure syndromes (BMFS) who are heavily transfused and often HLA-alloimmunized. Fifty-six patients with BMFS underwent fludarabine-based reduced-intensity conditioning and allogeneic peripheral blood progenitor cell (PBPC) transplantation at a single institution. The conditioning regimen consisted of intravenous cyclophosphamide, fludarabine, and equine antithymocyte globulin. Graft-versus-host disease (GVHD) prophylaxis included cyclosporine A alone or in combination with either mycophenolate mofetil or methotrexate. To reduce the risk of graft-rejection/failure, unmanipulated G-CSF mobilized PBPCs obtained from an HLA-identical or single HLA-antigen mismatched relative were transplanted rather than donor bone marrow. Despite a high prevalence of pretransplant HLA-alloimmunization (41%) and a heavy prior transfusion burden, graft-failure did not occur with all patients having sustained donor lympho-hematopoietic engraftment. The cumulative incidence of grade II-IV acute-GVHD and chronic-GVHD was 51.8% and 72%, respectively; with 87.1% surviving at a median follow-up of 4.5 years. A multivariate analysis showed pretransplant alloimmunization and rapid donor T-cell engraftment (≥95% donor by day 30) were both significantly (P < 0.05) associated with the development of chronic-GVHD (adjusted HR 2.13 and 2.99, respectively). These data show fludarabine-based PBPC transplantation overcomes the risk of graft-failure in patients with BMFS, although rapid donor T-cell engraftment associated with this approach appears to increase the risk of chronic-GVHD. (Clinicaltrials.gov identifier: NCT00003838). Am. J. Hematol. 88:874-882, 2013.

Original languageEnglish (US)
Pages (from-to)874-882
Number of pages9
JournalAmerican Journal of Hematology
Volume88
Issue number10
DOIs
StatePublished - Oct 1 2013

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Cell Transplantation
Graft vs Host Disease
Blood Cells
Tissue Donors
T-Lymphocytes
Graft Rejection
Cyclophosphamide
Stem Cells
Mycophenolic Acid
Transplants
Antilymphocyte Serum
Granulocyte Colony-Stimulating Factor
HLA Antigens
Methotrexate
Cyclosporine
Horses
Multivariate Analysis
Bone Marrow
Bone Marrow failure syndromes
Incidence

ASJC Scopus subject areas

  • Hematology

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Rapid donor T-cell engraftment increases the risk of chronic graft-versus-host disease following salvage allogeneic peripheral blood hematopoietic cell transplantation for bone marrow failure syndromes. / Pantin, Jeremy Mark; Tian, Xin; Shah, Avni A.; Kurlander, Roger; Ramos, Catalina; Cook, Lisa; Khuu, Hahn; Stroncek, David; Leitman, Susan; Barrett, John; Donohue, Theresa; Young, Neal S.; Geller, Nancy; Childs, Richard W.

In: American Journal of Hematology, Vol. 88, No. 10, 01.10.2013, p. 874-882.

Research output: Contribution to journalArticle

Pantin, JM, Tian, X, Shah, AA, Kurlander, R, Ramos, C, Cook, L, Khuu, H, Stroncek, D, Leitman, S, Barrett, J, Donohue, T, Young, NS, Geller, N & Childs, RW 2013, 'Rapid donor T-cell engraftment increases the risk of chronic graft-versus-host disease following salvage allogeneic peripheral blood hematopoietic cell transplantation for bone marrow failure syndromes', American Journal of Hematology, vol. 88, no. 10, pp. 874-882. https://doi.org/10.1002/ajh.23526
Pantin, Jeremy Mark ; Tian, Xin ; Shah, Avni A. ; Kurlander, Roger ; Ramos, Catalina ; Cook, Lisa ; Khuu, Hahn ; Stroncek, David ; Leitman, Susan ; Barrett, John ; Donohue, Theresa ; Young, Neal S. ; Geller, Nancy ; Childs, Richard W. / Rapid donor T-cell engraftment increases the risk of chronic graft-versus-host disease following salvage allogeneic peripheral blood hematopoietic cell transplantation for bone marrow failure syndromes. In: American Journal of Hematology. 2013 ; Vol. 88, No. 10. pp. 874-882.
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abstract = "The risk of graft-rejection after allogeneic hematopoietic cell transplantation using conventional cyclophosphamide-based conditioning is increased in patients with bone marrow failure syndromes (BMFS) who are heavily transfused and often HLA-alloimmunized. Fifty-six patients with BMFS underwent fludarabine-based reduced-intensity conditioning and allogeneic peripheral blood progenitor cell (PBPC) transplantation at a single institution. The conditioning regimen consisted of intravenous cyclophosphamide, fludarabine, and equine antithymocyte globulin. Graft-versus-host disease (GVHD) prophylaxis included cyclosporine A alone or in combination with either mycophenolate mofetil or methotrexate. To reduce the risk of graft-rejection/failure, unmanipulated G-CSF mobilized PBPCs obtained from an HLA-identical or single HLA-antigen mismatched relative were transplanted rather than donor bone marrow. Despite a high prevalence of pretransplant HLA-alloimmunization (41{\%}) and a heavy prior transfusion burden, graft-failure did not occur with all patients having sustained donor lympho-hematopoietic engraftment. The cumulative incidence of grade II-IV acute-GVHD and chronic-GVHD was 51.8{\%} and 72{\%}, respectively; with 87.1{\%} surviving at a median follow-up of 4.5 years. A multivariate analysis showed pretransplant alloimmunization and rapid donor T-cell engraftment (≥95{\%} donor by day 30) were both significantly (P < 0.05) associated with the development of chronic-GVHD (adjusted HR 2.13 and 2.99, respectively). These data show fludarabine-based PBPC transplantation overcomes the risk of graft-failure in patients with BMFS, although rapid donor T-cell engraftment associated with this approach appears to increase the risk of chronic-GVHD. (Clinicaltrials.gov identifier: NCT00003838). Am. J. Hematol. 88:874-882, 2013.",
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AU - Ramos, Catalina

AU - Cook, Lisa

AU - Khuu, Hahn

AU - Stroncek, David

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