Analysis of late graft failure after allogeneic bone marrow transplantation: detection of residual host cells using amplification of variable number of tandem repeats loci.

In an attempt to gain insight into the etiology of late graft failure, we analysed the origin of bone marrow mononuclear cells (BMMC) and peripheral blood leukocytes in patients with this syndrome by taking advantage of DNA fragment length polymorphisms in variable number of tandem repeats (VNTR) loci. Amplification of the VNTR loci in DNA from BMMC using the polymerase chain reaction revealed the persistence of host cells in two of four patients studied. One of the patients, whose cultured lymphocytes inhibited in vitro growth of donor-derived hemopoietic progenitor cells, responded to immunosuppressive therapy and donor-derived hemopoiesis was restored. In the other patient, host-derived polymorphonuclear leukocytes (PMN) appeared together with donor-derived PMN from the early post-transplant period, and he proceeded to relapse with myelodysplastic syndrome. In the other two patients in whom host cells were not detectable, the marrow hypoplasia was associated with chronic graft-versus-host disease (GVHD). The hypoplasia improved significantly as the chronic GVHD improved in response to immunosuppressive therapy. We conclude that detecting minimal residual host cells by means of amplification of VNTR loci is valuable for understanding the etiology of late graft failure in marrow transplant recipients, and could prove helpful for choosing appropriate therapy for this syndrome.