TY - JOUR
T1 - 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
AU - Lawler, Mark
AU - McCann, Shaun R.
AU - Marsh, Judith C. W.
AU - Ljungman, Per
AU - Hows, Jill
AU - Vandenberghe, Elisabeth
AU - O'Riordan, Joan
AU - Locasciulli, Anna
AU - Socié, Gérard
AU - Kelly, Alan
AU - Schrezenmeier, Hubert
AU - Marin, Pedro
AU - Tichelli, André
AU - Passweg, Jakob R.
AU - Dickenson, Anne
AU - Ryan, Jacqueline
AU - Bacigalupo, Andrea
PY - 2009/3
Y1 - 2009/3
N2 - 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.
AB - 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.
KW - CLINICAL-BIOLOGICAL SITUATIONS
KW - CHRONIC MYELOGENOUS LEUKEMIA
KW - CORD BLOOD TRANSPLANTATION
KW - MINIMAL RESIDUAL DISEASE
KW - ACUTE LYMPHOBLASTIC-LEUKEMIA
KW - POLYMERASE-CHAIN-REACTION
KW - graft failure
KW - aplastic anaemia
KW - chimerism
KW - QUANTITATIVE-ANALYSIS
KW - LONG-TERM SURVIVORS
KW - short tandem repeat
KW - BONE-MARROW-TRANSPLANTATION
KW - VERSUS-HOST-DISEASE
KW - allogeneic stem cell transplantation
KW - polymerase chain reaction
U2 - 10.1111/j.1365-2141.2008.07533.x
DO - 10.1111/j.1365-2141.2008.07533.x
M3 - Article
C2 - 19183198
SN - 0007-1048
VL - 144
SP - 933
EP - 945
JO - British Journal of Haematology
JF - British Journal of Haematology
IS - 6
ER -