Mapping of susceptibility and protective loci for acute GVHD in unrelated HLA-matched bone marrow transplantation donors and recipients using 155 microsatellite markers on chromosome 22

Despite matching donors and recipients for the human leukocyte antigens (HLAs) expressed by the major histocompatibility genomic region of the short arm of chromosome 6, several recipients still develop acute graft-versus-host disease (aGVHD) after bone marrow transplantation (BMT). This is possibly due to non-HLA gene polymorphisms, such as minor histocompatibility antigens (mHas) and genes coding for cytokines. However, a detailed genetic background for aGVHD has not yet been established. To find novel susceptibility and/or protective loci for aGVHD, a whole genome-wide association study of donors and recipients needs to be performed. As the first step to such a study, we retrospectively analyzed polymorphisms of 155 microsatellite markers spread across the long arm of chromosome 22 in 70 pairs of HLA-matched unrelated BMT donors and recipients. We performed individual typing and then compared the markers’ allele frequencies (1) between all the aGVHD (grades III and IV GVHD) and GVHD-free (grade 0 GVHD) groups in donors and recipients and (2) between the aGVHD and aGVHD-free groups in donor/recipient pairs that were matched and mismatched for the microsatellite marker’s allele. Screening of the microsatellite markers revealed five loci with a significant difference between the aGVHD and GVHD-free groups and revealed eight loci on chromosome 22, where the microsatellite allele mismatched markers were associated with aGVHD. This screening analysis suggests that several aGVHD-associated susceptible and protective loci exist on chromosome 22, which may encompass novel gene regions that need to be elucidated for their role in aGVHD.     

Bone-marrow transplantation for severe aplastic anaemia using histocompatible unrelated volunteer donors.

Two patients with severe aplastic anaemia received bone-marrow transplants from unrelated donors selected for HLA compatibility. Graft-versus-host disease occurred in both patients but responded to treatment. Both patients had stormy courses after grafting, but subsequently their conditions improved, and one was not receiving any treatment at follow-up after day 330 while the other had mild chronic graft-versus-host disease at day 150. These results show that unrelated, histocompatible volunteers may successfully donate marrow for the treatment of severe aplastic anaemia, though many problems remain to be solved.     

Recruiting unrelated donors for the National Marrow Donor Program

Medical advances have made bone marrow transplantation the treatment of choice for certain hematologic diseases. For those patients eligible for a marrow transplant only about 30 percent find an HLA-compatible match within their families. Studies indicate that unrelated volunteers are willing to donate their marrow. The National Marrow Donor Program was formed in 1986 as a result of a federal contract. This group is a network of donor centers, transplant centers, and collection centers. The Connecticut Red Cross Blood Services is one of approximately 70 donor centers. Recruitment methods vary with each donor center, depending on the resources available. The Connecticut Red Cross Blood Services has recruited more than 1,000 volunteers for entry into the National Marrow Donor Program.     

Current status of bone marrow transplantation in humans: report from the International Bone Marrow Transplant Registry

Bone marrow transplantation is being used with increasing frequency as therapy for a number of life-threatening diseases. Data reported to the International Bone Marrow Transplant Registry are presented to show the pattern of growth of bone marrow transplantation worldwide as well as current results in leukemia and aplastic anemia. Risk factors are identified that may predict the development of major complications after bone marrow transplantation.     

Correction of a T-immunodeficit in mice by bone marrow transplantation from donors treated with hydrocortisone]

Adult CBA mice were exposed to thymectomy, lethal irradiation, and protection by syngeneic bone marrow transplantation. In some experiments syngeneic bone marrow of donors, treated with hydrocortisone in a dose of 125 mg/kg for 3 days was used. The bone marrow of these donors contained cells with the Q-marker. Thymectomized and lethally irradiated animals subjected to the transplantation of syngeneic bone marrow from hydrocortisone-treated donors rejected the skin allotransplants, and the lymph node cells of these mice suppressed the endogenous colony-formation in the sublethally-irradiated hybrids (CBA X C57Bl/6) F1.