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

Br J Haematol. 2009 Mar;144(6):933-45. doi: 10.1111/j.1365-2141.2008.07533.x. Epub 2009 Jan 9.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Anemia, Aplastic / genetics
  • Anemia, Aplastic / mortality
  • Anemia, Aplastic / therapy*
  • Child
  • Child, Preschool
  • Chimerism
  • Cyclosporine / therapeutic use
  • Fanconi Anemia / genetics
  • Fanconi Anemia / mortality
  • Fanconi Anemia / therapy
  • Female
  • Follow-Up Studies
  • Graft Rejection*
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Male
  • Middle Aged
  • Polymerase Chain Reaction / methods
  • Prognosis
  • Proportional Hazards Models
  • Recurrence
  • Stem Cell Transplantation / adverse effects*
  • Survival Rate
  • Tandem Repeat Sequences
  • Time Factors
  • Transplantation Conditioning
  • Transplantation, Homologous
  • Young Adult

Substances

  • Immunosuppressive Agents
  • Cyclosporine