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

被引:71
作者
Lawler, Mark [1 ]
McCann, Shaun R. [1 ]
Marsh, Judith C. W. [13 ]
Ljungman, Per [2 ]
Hows, Jill [12 ]
Vandenberghe, Elisabeth [1 ]
O'Riordan, Joan [1 ]
Locasciulli, Anna [3 ]
Socie, Gerard [4 ,11 ]
Kelly, Alan [5 ]
Schrezenmeier, Hubert [6 ]
Marin, Pedro [7 ]
Tichelli, Andre [8 ]
Passweg, Jakob R. [8 ]
Dickenson, Anne [10 ]
Ryan, Jacqueline [1 ]
Bacigalupo, Andrea [9 ]
机构
[1] St James Hosp, Dept Haematol, Durkan Res Lab, Inst Mol Med, Dublin 8, Ireland
[2] Huddinge Univ Hosp, Karolinska Inst, Dept Med, S-14186 Huddinge, Sweden
[3] Osped San Camilla, Rome, Italy
[4] Hop St Louis, Unite Biol Cellules Souches, Paris, France
[5] Trinity Coll Dublin, Dept Community Hlth, Dublin, Ireland
[6] Univ Ulm, Inst Clin Transfus Med & Immunogenet, Ulm, Germany
[7] Hosp Clin I Prov Barcelona, Postgrad Sch Haematol, Barcelona, Spain
[8] Kantonsspital, Dept Internal Med, Div Haematol, CH-4031 Basel, Switzerland
[9] Osped San Martino Genova, Div Ematol, Ctr Trapianti Midollo Osseo, Genoa, Italy
[10] Newcastle Univ, Dept Haematol, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England
[11] Hop San Louis, Serv Greffe Moelle, Paris, France
[12] Univ Bristol, Div Transplantat Sci, Bristol, Avon, England
[13] Univ London St Georges Hosp, Sch Med, Dept Cellular & Mol Sci, Div Haematol, London SW17 0RE, England
关键词
chimerism; aplastic anaemia; allogeneic stem cell transplantation; graft failure; short tandem repeat; polymerase chain reaction; BONE-MARROW-TRANSPLANTATION; VERSUS-HOST-DISEASE; CLINICAL-BIOLOGICAL SITUATIONS; CHRONIC MYELOGENOUS LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; CORD BLOOD TRANSPLANTATION; POLYMERASE-CHAIN-REACTION; MINIMAL RESIDUAL DISEASE; LONG-TERM SURVIVORS; QUANTITATIVE-ANALYSIS;
D O I
10.1111/j.1365-2141.2008.07533.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:933 / 945
页数:13
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