Serial chimerism analyses indicate that mixed haemopoietic chimerism influences the probability of graft rejection and disease recurrence following allogeneic stem cell transplantation (SCT) for severe aplastic anaemia (SAA): indication for routine assessment of chimerism post SCT for SAA

Mark Lawler*, Shaun R. McCann, Judith C. W. Marsh, Per Ljungman, Jill Hows, Elisabeth Vandenberghe, Joan O'Riordan, Anna Locasciulli, Gérard Socié, Alan Kelly, Hubert Schrezenmeier, Pedro Marin, André Tichelli, Jakob R. Passweg, Anne Dickenson, Jacqueline Ryan, Andrea Bacigalupo

*Corresponding author for this work

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Abstract

Ninety-one patients were studied serially for chimeric status following allogeneic stem cell transplantation (SCT) for severe aplastic anaemia (SAA) or Fanconi Anaemia (FA). Short tandem repeat polymerase chain reaction (STR-PCR) was used to stratify patients into five groups: (A) complete donor chimeras (n = 39), (B) transient mixed chimeras (n = 15) (C) stable mixed chimeras (n = 18), (D) progressive mixed chimeras (n = 14) (E) recipient chimeras with early graft rejection (n = 5). As serial sampling was not possible in Group E, serial chimerism results for 86 patients were available for analysis. The following factors were analysed for association with chimeric status: age, sex match, donor type, aetiology of aplasia, source of stem cells, number of cells engrafted, conditioning regimen, graft-versus-host disease (GvHD) prophylaxis, occurrence of acute and chronic GvHD and survival. Progressive mixed chimeras (PMCs) were at high risk of late graft rejection (n = 10, P <0.0001). Seven of these patients lost their graft during withdrawal of immunosuppressive therapy. STR-PCR indicated an inverse correlation between detection of recipient cells post-SCT and occurrence of acute GvHD (P = 0.008). PMC was a bad prognostic indicator of survival (P = 0.003). Monitoring of chimeric status during cyclosporin withdrawal may facilitate therapeutic intervention to prevent late graft rejection in patients transplanted for SAA.

Original languageEnglish
Pages (from-to)933-945
Number of pages13
JournalBritish Journal of Haematology
Volume144
Issue number6
DOIs
Publication statusPublished - Mar 2009

Keywords

  • CLINICAL-BIOLOGICAL SITUATIONS
  • CHRONIC MYELOGENOUS LEUKEMIA
  • CORD BLOOD TRANSPLANTATION
  • MINIMAL RESIDUAL DISEASE
  • ACUTE LYMPHOBLASTIC-LEUKEMIA
  • POLYMERASE-CHAIN-REACTION
  • graft failure
  • aplastic anaemia
  • chimerism
  • QUANTITATIVE-ANALYSIS
  • LONG-TERM SURVIVORS
  • short tandem repeat
  • BONE-MARROW-TRANSPLANTATION
  • VERSUS-HOST-DISEASE
  • allogeneic stem cell transplantation
  • polymerase chain reaction

Cite this

Lawler, M., McCann, S. R., Marsh, J. C. W., Ljungman, P., Hows, J., Vandenberghe, E., O'Riordan, J., Locasciulli, A., Socié, G., Kelly, A., Schrezenmeier, H., Marin, P., Tichelli, A., Passweg, J. R., Dickenson, A., Ryan, J., & Bacigalupo, A. (2009). Serial chimerism analyses indicate that mixed haemopoietic chimerism influences the probability of graft rejection and disease recurrence following allogeneic stem cell transplantation (SCT) for severe aplastic anaemia (SAA): indication for routine assessment of chimerism post SCT for SAA. British Journal of Haematology, 144(6), 933-945. https://doi.org/10.1111/j.1365-2141.2008.07533.x