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.
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.
Lawler
Mark
M
Durkan Research Laboratories, Department of Haematology, Institute of Molecular Medicine, St James's Hospital and Trinity College, Dublin, Ireland. mplawler@tcd.ie
McCann
Shaun R
SR
Marsh
Judith C W
JC
Ljungman
Per
P
Hows
Jill
J
Vandenberghe
Elisabeth
E
O'Riordan
Joan
J
Locasciulli
Anna
A
Socié
Gérard
G
Kelly
Alan
A
Schrezenmeier
Hubert
H
Marin
Pedro
P
Tichelli
André
A
Passweg
Jakob R
JR
Dickenson
Anne
A
Ryan
Jacqueline
J
Bacigalupo
Andrea
A
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
D007166:Immunosuppressive Agents; D016572:Cyclosporine