Highly sensitive polymerase chain reaction methods show the frequent survival of residual recipient multipotent progenitors after non-T-cell-depleted bone marrow transplantation.
Twenty-four male patients grafted for various pathologies with the marrow of a female donor and presenting a complete donor-type hematopoiesis when analyzed by polymerase chain reaction (PCR) amplification of minisatellite sequences 33.6.3 and MS51 (0.1% to 1% sensitivity) were studied by the highly sensitive technique of PCR amplification of the Y-chromosome-specific DYZ1 sequence (0.01% sensitivity). Residual recipient male cells were detected in all peripheral blood samples collected within 1 year posttransplantation. These residual cells were present in both the lymphocyte and polymorphonuclear cell fractions when such a separation was performed by Ficoll gradient centrifugation and, for samples of 13 of 15 patients, at comparable levels in both fractions. In 3 samples collected from 3 patients 4 months or more posttransplantation, residual recipient cells were detected in the polymorphonuclear cell fraction but were present at a lower level or were undetectable in the lymphocyte fraction. These cells are of hematopoietic origin because they were detected at equivalent levels in whole blood and in B and T lymphocytes sorted with antibody-coated magnetic beads. They were not detected in samples collected more than 15 months posttransplantation for 6 of 7 patients. The persistence of residual recipient cells within 1 year posttransplantation is not restricted to male patients receiving a transplant from a female donor because they were also detected in 2 female patients using an allele-specific amplification method for the thyroid peroxydase gene that also has a high sensitivity (0.01%). Our results indicate that at least residual recipient myeloid progenitors and possibly totipotent hematopoietic stem cells may survive intensive pretransplant conditioning regimen and support a transient residual hematopoiesis of the host posttransplantation.
Petit
T
T
Laboratoire d'Oncologie Moléculaire, URA 1158 CNRS, Institut Gustave Roussy, Villejuif, France.
Raynal
B
B
Socié
G
G
Landman-Parker
J
J
Bourhis
J H
JH
Gluckman
E
E
Pico
J
J
Brison
O
O
D000293:Adolescent; D000328:Adult; D000741:Anemia, Aplastic / Q000628:therapy; D001402:B-Lymphocytes / Q000166:cytology*; D001483:Base Sequence; D015139:Blotting, Southern; D016026:Bone Marrow Transplantation / Q000276:immunology*; D002469:Cell Separation; D002648:Child; D002675:Child, Preschool; D017931:DNA Primers; D005199:Fanconi Anemia / Q000628:therapy; D005260:Female; D006085:Graft Survival; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D007938:Leukemia / Q000628:therapy; D008214:Lymphocytes / Q000166:cytology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000166:cytology / Q000473:pathology; D016133:Polymerase Chain Reaction / Q000379:methods*; D011110:Polymorphism, Genetic; D012680:Sensitivity and Specificity; D013601:T-Lymphocytes / Q000166:cytology*; D014184:Transplantation, Homologous; D014998:Y Chromosome
D017931:DNA Primers