Serial quantification of lymphoid and myeloid mixed chimerism using multiplex PCR amplification of short tandem repeat-markers predicts graft rejection and relapse, respectively, after allogeneic transplantation of CD34+ selected cells from peripheral blood.
We used multiplex amplification of nine microsatellite sequences (PCR-STR) to analyse chimerism in pure populations of T cells and neutrophils from peripheral blood from 40 patients submitted to an allogeneic transplant, 22 having received a T-cell depleted (TCD) peripheral blood graft by means of CD34(+) selection (allo-PBT/CD34(+)), and 18, an unmodified graft (allo-SCT; 13 allogeneic bone marrow transplants and five allo-PBT). T-cell mixed chimerism (TcMC) was observed in 16 of the 22 (72.3%) patients receiving an allo-PBT/CD34(+), but in only one of the 18 (5.5%) patients receiving an allo-SCT (P=0.0001). TcMC was transient (n=6), stable (n=7), and associated with poor haematopoietic engraftment (n=4). All patients with TcMC who developed graft failure had more than 30% of host T cells. Myeloid MC (MyMC) was observed in four (19%) allo-PBT/CD34(+) patients and in three (17%) allo-SCT patients (P=NS). Five out of seven (71%) patients with MyMC relapsed, all of them diagnosed with myeloid malignancies, as compared with two of the 20 (10%) patients with complete donor chimerism (P&<0.0001). In conclusion, TcMC appears in a significant number of allo-PBT/CD34(+) patients and may be associated with poor engraftment when the percentage of host T cells is >30%; likewise, MyMC appears in a small percentage of recipients of both allo-PBT/CD34(+) and allo-SCT patients, and is associated with leukaemia relapse in myeloid malignancies.
Fernández-Avilés
F
F
Institute of Haematology and Oncology, Hospital Clínic of Barcelona, University of Bacelona, Spain.
Urbano-Ispizua
A
A
Aymerich
M
M
Colomer
D
D
Rovira
M
M
Martínez
C
C
Nadal
E
E
Talarn
C
C
Carreras
E
E
Montserrat
E
E
D000328:Adult; D018952:Antigens, CD34; D016026:Bone Marrow Transplantation / Q000379:methods / Q000592:standards; D005260:Female; D006084:Graft Rejection; D006801:Humans; D007938:Leukemia / Q000628:therapy; D007962:Leukocytes / Q000166:cytology*; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D022423:Myeloid Cells / Q000166:cytology*; D036102:Peripheral Blood Stem Cell Transplantation / Q000379:methods / Q000592:standards*; D016133:Polymerase Chain Reaction / Q000379:methods* / Q000592:standards; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012008:Recurrence; D020080:Tandem Repeat Sequences; D018183:Transplantation Chimera; D014184:Transplantation, Homologous / Q000379:methods / Q000592:standards
D018952:Antigens, CD34