Treatment of severe aplastic anaemia with antilymphocyte globulin or bone-marrow transplantation.

Abstract

Fifty-three patients with severe aplastic anaemia were admitted to this hospital between January 1976 and June 1980, of whom three arrived in terminal condition and died before treatment for their basic disease could be given. Thus 50 patients were treated and evaluated in a prospective study according to one protocol. Eighteen patients with an HLA-identical sibling underwent bonemarrow transplantation with the aim of achieving haematopoietic chimerism. Thirty-two patients without an HLA-identical sibling were given antilymphocyte globulin with or without an infusion of HLA-haplotypeidentical marrow. All these 32 patients received low-dose androgens after the procedure. In the first group eight

Positive Direct Antiglobulin Tests and Heteroimmune Hemolysis in Patients with Severe Aplastic Anemia and Pure Red Cell Anemia Treated with Antilymphocytic Globulin

“…However, the potency of the antiserum appears to be crucial to response. A dose-response relationship in the treatment of SAA has been established recently [34], and a synergism with glycocorticoids appears very probable [9,10], as already suggested in earlier studies [35]. The overall titer is probably also less im portant than the combination of antibodies present against various subpopulations of T or perhaps even B lymphocytes, as therapeutic results in predomi nantly B-autoimmune diseases, notably PRCA, would suggest [16].…”

“…A series of clinical phase-II trials [3][4][5][6][7][8][9][10], which were further corroborated by two ran domized studies [11,12], showed the ability of ALG/ ATG to promote nearly total or more often partial reconstitution of hemopoiesis in a varying percentage of patients. The combination with glycocorticoids (6-methylprednisolone), especially in high dosage, was found to improve the response rate in 1 series [9], However, in the most recent and extensive review of the European Bone Marrow Transplantation Work ing Party on SAA, an overall actuarial survival of 50% at 4 years was established, with no special effect of the immunosuppressive protocol on the outcome [13], ALG/ATG has been employed with variable success in a series of diseases with immunological fea tures [1,14], especially in pure red cell aplasia (PRCA) [15,16], While there is no discussion on the way ALG/ ATG and immunosuppression (IS) in general are conducive to remission in PRCA [15], there is still considerable controversy as to its mechanism of ac tion in SAA, reflecting the well-known problems in the etiology and pathogenesis of the disease [17][18][19]. The term IS itself generally suggests that ALG/ATG acts by inhibiting activated T suppressor cells in SAA [20], thus reducing their output of inhibitory lymphokine-like molecules [20][21][22], Yet, an enhancing effect on growth-promoting factors has also been hypothes ized [23][24][25].…”

Differentiation of normal marrow and HL60 cells induced by antithymocyte globulin.

“…Five to 10% human placental conditioned medium prepared by the method of Schlunk and Schleyer (10) was added as a source of colony-stimulating factor (CSF). ATG at various concentrations (1)(2)(3)(4)(5)(6)(7)(8)(9)(10) Cells were suspended at a concentration of 1 x 105 per ml and incubated with various concentrations ofATG for 6 days, at which time the control cultures began to deteriorate. Cells were harvested daily for morphologic examination and viability by using trypan blue exclusion.…”

“…Autologous hematologic reconstitution occurs in 50-74% of patients receiving these preparations (6,7). The mechanism for the hematologic recovery in these responding patients is unknown.…”

The optimal immunosuppressive therapy for aplastic anemia

“…Current standard immunosuppressive regimen; horse ATG with cyclosporine A Since pioneering trials which showed immunosuppression by horse ATG alone without infusing allogeneic BM as the effective treatment for patients with AA [21,22], subsequent studies which showed response rates of 30-70 % confirmed that horse ATG was a feasible therapeutic option for patients with AA who are not eligible for allogeneic SCT [23][24][25][26].…”