MARROW transplantation between genotypically HLA-identical siblings has an established and expanding place in the management of leukemia and aplastic anemia.1 2 3 The majority of patients, unfortun...

Transplantation of marrow from an unrelated donor to a patient with acute leukemia.

Association between pre-transplant natural kill and graft-versus-host disease after stem-cell transplantation.

Functional and phenotypic heterogeneity of human T lymphocytes is now well established. T lymphocytes are subdivided into two major functional categories, namely effector T cells that mediate the functions of cell-mediated immunity, and immunoregulatory T cells comprised of helpers and suppressors, influencing the differentiation of B cells to immunoglobulin synthesizing and secreting plasma cells and regulating the responses of effector T cells. These immunoregulatory T cell subpopulations are identified by certain characteristics. They include the presence of distinct differentiation antigens as defined by heteroantisera or monoclonal antibodies developed by hybridoma technique, by the sensitivity or resistance of the cells to inhibition of rosette formation by theophylline (theophylline sensitive and theophylline resistant) and by the presence of receptors for immunoglobulin isotypes. Receptors for Fc region of IgM, IgG, IgA, IgE, IgD have been described on T lymphocytes (Gupta 1978, Gupta & Good 1980a,1978c, Moretta et al. 1978a, Gupta et al. 1980a). However, these receptors are also present on B lymphocytes (Gupta et al. 1979b, Gupta et al. 1979h). T cells with IgM Fc receptors (T[i) contain cells with helper activity for the differentiation of B cells into immunoglobulin synthesizing and secreting plasma cells in pokeweed and antigen-driven systems; T cells with IgG Fc receptors (Ty) contain cells with suppressor activity in a similar system (discussed in detail in this volume elsewhere). In this section we will review some of the functional properties of T cell subsets defined by the presence of receptors for immunoglobulin isotypes and their distribution in a variety of primary and secondary immunodeficiency disorders.

Subpopulations of Human T Lymphocytes: Laboratory and Clinical Studies

Between February 1971 and October 1980, 34 patients with leukemia or aplastic anemia received bone marrow transplants from HLA-identical siblings whose lymphocytes did not react in a mixed leukocyte culture. The donors of 10 patients were ABO-incompatible, and for five pairs the ABO incompatibility was major. Plasma exchanges followed by a red blood cell exchange transfusion reduced the anti-A titres to 1:4 or less in these patients. The ABO incompatibility had no adverse effect on the results of marrow transplantation. Twenty-two patients, including 16 of the 20 who received their transplant after Jan. 1, 1980, are still living. Seven of the 15 patients with acute leukemia have survived 89 to 466 days, and 4 of the 6 with chronic myelogenous leukemia (CML) have survived 117 to 545 days. Of the 13 patients with aplastic anemia, 11 are alive up to 8 years after transplantation. Marrow transplantation, when possible, is the treatment of choice for young patients with acute leukemia in remission and for patients with aplastic anemia. Marrow transplantation may also prove to be effective in patients with CML.

Bone marrow transplantation for leukemia and aplastic anemia: management of ABO incompatibility.

The importance for marrow transplantation of compatibility between donor and recipient for the genetic determinants of the Major Histocompatibility Complex (MHC) has been evident since the early studies in mice (Uphoff and Law, 1958). The innoculation of immunocompetent cells into allogeneic immunoincompetent recipients leads to the development of the graft-versus-host reaction (GvHR). The classical GvHR model has been the injection of parental cells into F1 hybrid mice (Simonsen, 1962; Elkins, 1971). The H-2 complex involvement in GvHR is well established.

Histocompatibility Testing for Clinical Bone Marrow Transplantation and Prospects for Identification of Donors Other than HLA Genotypically Identical Siblings

A patient with aplastic anemia who was found to be homozygous for an HLA-D determinant shared by her unrelated parents achieved sustained engraftment and full restoration of hematopoietic and lymphoid function following a transplant from an HLA-A and -B nonidentical, ABO incompatible sibling who was heterozygous for the shared HLA-D specificity. Transplantation was complicated by transient graft-versus-host disease of moderate severity, which resolved completely following treatment with antithymocyte globulin and prednisone. The case indicates that patients found to be HLA-D-homozygous may be successfully transplanted from HLA-D-heterozygous sibling donors despite HLA-A and HLA-B incompatibilities, and thus further demonstrates the importance of the HLA-D region as a marker of donor-host histocompatibility.

Successful transplantation of marrow from an HLA-A, -B, -D mismatched heterozygous sibling donor into an HLA-D-homozygous patient with aplastic anemia.

Immunoregulatory T cells in patients with primary immunodeficiency diseases.

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Successful transplantation of marrow from an HLA-A, -B, -D mismatched heterozygous sibling donor into an HLA-D-homozygous patient with aplastic anemia.

Immunoregulatory T cells in patients with primary immunodeficiency diseases.