title: 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.
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.
authors.affiliation: Durkan Research Laboratories, Department of Haematology, Institute of Molecular Medicine, St James's Hospital and Trinity College, Dublin, Ireland. mplawler@tcd.ie
authors.forename: Mark
authors.initials: M
authors.lastname: Lawler
authors.forename: Shaun R
authors.initials: SR
authors.lastname: McCann
authors.forename: Judith C W
authors.initials: JC
authors.lastname: Marsh
authors.forename: Per
authors.initials: P
authors.lastname: Ljungman
authors.forename: Jill
authors.initials: J
authors.lastname: Hows
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Vandenberghe
authors.forename: Joan
authors.initials: J
authors.lastname: O'Riordan
authors.forename: Anna
authors.initials: A
authors.lastname: Locasciulli
authors.forename: Gérard
authors.initials: G
authors.lastname: Socié
authors.forename: Alan
authors.initials: A
authors.lastname: Kelly
authors.forename: Hubert
authors.initials: H
authors.lastname: Schrezenmeier
authors.forename: Pedro
authors.initials: P
authors.lastname: Marin
authors.forename: André
authors.initials: A
authors.lastname: Tichelli
authors.forename: Jakob R
authors.initials: JR
authors.lastname: Passweg
authors.forename: Anne
authors.initials: A
authors.lastname: Dickenson
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Ryan
authors.forename: Andrea
authors.initials: A
authors.lastname: Bacigalupo
mesh_terms: D000293:Adolescent; D000328:Adult; D000741:Anemia, Aplastic / Q000235:genetics / Q000401:mortality / Q000628:therapy*; D002648:Child; D002675:Child, Preschool; D046528:Chimerism; D016572:Cyclosporine / Q000627:therapeutic use; D005199:Fanconi Anemia / Q000235:genetics / Q000401:mortality / Q000628:therapy; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods; D011379:Prognosis; D016016:Proportional Hazards Models; D012008:Recurrence; D033581:Stem Cell Transplantation / Q000009:adverse effects*; D015996:Survival Rate; D020080:Tandem Repeat Sequences; D013997:Time Factors; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine