Chimerism studies using in situ hybridization for the Y chromosome after T cell-depleted bone marrow transplantation.
In situ hybridization for the Y chromosome (Y-ISH) was used to monitor engraftment in 10 patients with hematological malignancies who had received T cell-depleted marrow transplants from sex-mismatched donors, seven of whom were only partially HLA-matched. In the three patients who engrafted, as the peripheral counts rose, the percentage of host peripheral blood and marrow mononuclear cells decreased steadily, although host cells (less than 1%) could still be detected as late as day 252. The percentage of host granulocytes fell rapidly to less than 0.2%. Seven patients did not achieve full engraftment by day 28. Those with a low percentage of host cells (less than 1%) improved with observation or treatment with steroids, while those with a high or increasing percentage of host cells did not improve even after treatment with GM-CSF or with repeat marrow infusion without reconditioning. In one patient with graft failure, the residual host cells were predominantly CD8+ CD57+ and CD3+ CD56+, phenotypes consistent with non-MHC-restricted cytotoxic T cells. Lack of full engraftment in recipients of T cell-depleted marrow is not always associated with autologous reconstitution and does not always require retransplantation. Y-ISH may be useful for monitoring patients at high risk for graft failure in order to detect adverse trends in mixed chimerism that will alter therapy early after transplantation.
Przepiorka
D
D
Pittsburgh Cancer Institute Adult Bone Marrow Transplant Program, PA.
Gonzales-Chambers
R
R
Winkelstein
A
A
Rosenfeld
C
C
Shadduck
R K
RK
D000293:Adolescent; D000328:Adult; D000954:Antigens, Surface / Q000276:immunology; D016026:Bone Marrow Transplantation / Q000276:immunology / Q000473:pathology*; D002462:Cell Membrane / Q000276:immunology / Q000648:ultrastructure; D002678:Chimera / Q000235:genetics* / Q000276:immunology; D004247:DNA / Q000032:analysis / Q000235:genetics* / Q000648:ultrastructure; D005260:Female; D005434:Flow Cytometry; D006084:Graft Rejection; D006801:Humans; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D009693:Nucleic Acid Hybridization; D010641:Phenotype; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000648:ultrastructure; D014998:Y Chromosome / Q000032:analysis / Q000648:ultrastructure*
D000954:Antigens, Surface; D004247:DNA