HLA-DP genotyping in HLA-A,B, and DR identical intrafamilial bone marrow transplantation.

In a study carried out for patients receiving intrafamilial HLA-A,B,DR identical, MLC negative bone marrow transplants, RFLP profiles of HLA-class II for 27 donor recipient pairs were analyzed. Twenty-four pairs were found HLA-class II identical while three pairs were HLA-DP incompatible. The patients of these three pairs did not reveal any acute GVHD greater than or equal to grade II. The seven cases of acute GVHD greater than or equal to grade II found in our panel were HLA-DR, DQ, and DP compatible. Thus, in practical terms pretransplantation HLA-DP typing does not seem necessary for intrafamilial HLA-identical, MLC negative BMT. On the other hand, this work confirmed that it is possible to type for HLA-DP using molecular biological techniques, and this in itself may have some important implications for unrelated BMT.

Phenotype and function of T lymphocytes infiltrating the skin during graft-versus-host disease following allogeneic bone marrow transplantation.

Seven lymphocyte populations were expanded from skin samples of patients with acute or chronic GVHD following allogeneic genotypically identical BMT. After amplification without in vitro antigenic stimulation or addition of mitogens, 5 of the 7 cell lines showed a large majority of mature CD4+ T cells (in contrast to published immunopathological data). One cell line showed an equal number of CD4+ and CD8+ cells, and another a predominance of CD4+ cells along with a large number of cells with a phenotype suggestive of non-MHC-restricted CTLs. After in vitro antigenic stimulation, various cytotoxicity patterns were seen: specific antihost cytotoxicity was seen in half the cell lines, NK activity was seen in 5 of the 7 lines, and a strong LAK activity was seen in 1 of the 7 cell lines. These results point to a diversity of cytotoxic effectors involved locally in GVHD and emphasize the need for further study of these local events. The cell lines established now constitute basic functional material for the in vitro study of cellular and humoral interactions at the site of GVHD lesions.

Role of immunosuppressive drugs for prevention of graft-v-host disease after bone marrow transplantation.

In a series of 198 patients we compared various methods of prevention of GVHD. One hundred and thirty-three patients were treated with CSA alone, 44 with the combination of CSA and MTX, and 21 with CSA after marrow T cell depletion. The incidence of GVHD greater than or equal to II was 35% in the CSA group, 22% in the CSA+MTX group and 14% in the T depleted group. The actuarial survival was 55.4%, 52.3% and 55.1% respectively. These results show that the improvement of methods of prevention of GVHD did not affect significantly long term survival after BMT.

[Allogenic bone marrow grafts in chronic myeloid leukemia]. / La greffe de moelle osseuse allogénique dans la leucémie myéloïde chronique.

Between August 1979 and April 1986, we treated 70 patients with chronic myeloid leukemia by supralethal chemoradiotherapy followed by bone marrow transplantation (BMT) from HLA identical sibling donors (65 patients) or from identical twins (5 patients). All patients were splenectomized before BMT. To prevent graft versus host disease Cyclosporin alone or associated with Methotrexate was given; in addition 13 patients received a T cell depleted marrow. All patients showed engraftment. Of the 5 patients treated by syngenic BMT, 2 patients relapsed but all are alive in remission, 2 of them after a successful second BMT. Of the 36 patients treated by allogeneic BMT in the chronic phase, 20 are alive in unmaintained remission after a median follow-up of 24 months (range 6 to 58). No patients have relapsed. The actuarial survival at 2 years was 60%. Of the 29 patients with more advanced disease, 19 have survived with the actuarial survival at 2 years 50%. We conclude that the probability of cure after BMT is very high, especially if BMT is performed while the patient remains in the chronic phase. Only 3 patients grafted in accelerated or blast phase died with relapse. The main cause of death was interstitial pneumonitis (15 patients) and 10 patients died from other transplant-related complications.

[Immunity related to cytomegalovirus after allogenic bone marrow transplantation: role of donor immunity to cytomegalovirus in the incidence of cytomegalovirus infection in recipients]. / Immunité vis-à-vis du cytomégalovirus après greffe de moelle osseuse allogénique: Rôle de l'immunité du donneur vis-à-vis du cytomégalovirus dans l'incidence de l'infection à cytomégalovirus chez les receveurs.

Cytomegalovirus infections are severe and frequent after BMT. This study included 34 bone marrow transplant recipients (23 aplastic anaemias and 11 leukaemias), their marrow donors and 125 related or non related normal controls. Assays were performed before transplantation and every 30 days between D 0 and D 90, and then every six months. They included detection of CMV induced lymphocyte proliferation in vitro, CMV antibody determinations by complement fixation and reverse haemagglutination, viraemia and/or viruria. Similarly, cellular immunity to mitogens and to other specific antigens was evaluated. During the period of study, 22 patients developed CMV infection. The diagnostic was confirmed by virus isolation from the 12th to the 96th day after the graft. Development of positive CMV proliferation test occurred from the 9th to the 84th day after virus isolation (30 to 120th day after the graft). In one case, the CMV infection was only proved by the lymphocyte proliferation to CMV in vitro and only 60 days later by viruria and 105 days later by detection of CMV antibodies. For the other 12 patients (7 aplasies and 5 leukaemias) and 10 of their bone marrow donors, no CMV infection was proved, before or after transplant, by any of the assays performed. By selecting a donor without previous CMV infection, we hope to reduce the incidence of CM infection in recipients.