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Third-party-mediated graft rejection and graft-versus-host disease after T-cell-depleted bone marrow transplantation, as demonstrated by hypervariable DNA probes and HLA-DR polymorphism. Blood 1989 Nov 01;74(6):2285-94

Date

11/01/1989

Pubmed ID

2572285

DOI

10.1182/blood.v74.6.2285.2285

Scopus ID

2-s2.0-0024448687   63 Citations

Abstract

Graft rejection after marrow transplantation is generally thought to be mediated by alloreactive immune effector cells of host origin. Transfused blood products also contain immune cells capable of alloreactivity against both donor graft and host. To reduce the risk of transfusion-associated graft-versus-host disease (GVHD) and graft rejection, standard procedure is to irradiate all blood products with at least 1,500 rad before transfusion. We report a patient with chronic myelogenous leukemia who developed graft rejection and GVHD after receiving a T-cell-depleted transplant from a serologically HLA-A, B, DR/DQ matched and mixed lymphocyte culture (MLC) nonreactive unrelated donor. Cytogenetic analysis of marrow cells collected at the time of graft rejection revealed a PH1-negative female karyotype that was not consistent with donor cells. Use of specific minisatellite DNA probes (YNH 24, H-RAS, and 3' HVR) revealed the exclusive presence of third-party (neither donor nor recipient) restriction-fragment-length polymorphisms (RFLP) in both peripheral blood and marrow. Repeat RFLP analysis 3 days later showed persistence of this unique third-party banding pattern. DNA-based HLA-typing, using polymerase chain reaction (PCR) and oligonucleotide probe hybridization, also showed these cells to be derived from an individual whose HLA-DR type was distinct from donor and recipient. Together, these findings suggested the presence of a proliferating population of transfused cells possessing alloreactivity against both donor graft and host, despite prior irradiation of all blood products with 2,000 rad. Limiting dilution analysis to assess the frequency of irradiated lymphocytes able to respond to mitogen revealed an approximate 5- to 6-log reduction at 1,500 to 2,000 rad as compared with unirradiated controls. These data indicate that a small percentage of lymphocytes can survive irradiation at these doses and suggest that existing blood-product irradiation guidelines may require reassessment, especially in T-cell-depleted transplant recipients.

Author List

Drobyski W, Thibodeau S, Truitt RL, Baxter-Lowe LA, Gorski J, Jenkins R, Gottschall J, Ash RC

Author

William R. Drobyski MD Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Bone Marrow Transplantation
DNA Probes, HLA
Female
Graft Rejection
Graft vs Host Disease
HLA-DR Antigens
Karyotyping
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Oligonucleotide Probes
Polymerase Chain Reaction
Polymorphism, Restriction Fragment Length
T-Lymphocytes