Studies on Bone Marrow Transplantation in Experimental ³²P-Induced Aplastic Anemia after Conditioning with Antilymphocyte Serum

Abstract

Aplastic anemia was produced with ³²P in rabbits with and without splenectomy. Transient hemopoietic engraftment without graft versus host (GvH) was seen after conditioning with antilymphocyte serum (ALS) and infusion of allogeneic marrow from a strain that is known to cause fatal secondary disease if total body irradiation is used for conditioning. More takes could be achieved in the splenectomized group but in both groups the takes were only transient. The absence of GvH was shown to be probably due to a split chimerism of the immunologic system. The graft rejections are felt to be due to the persistence of host T cells. Possibly the duration of engraftment can be prolonged in the future by continued immunosuppressive therapy after transplantation with ALS or cyclophosphamide. The fact that the spleen is not necessary for hemopoietic recovery after i.v. marrow infusion may have important clinical implications because many patients with aplastic anemia are splenectomized in the course of their disease

Autologous Marrow Reconstitutions in Severe Aplastic Anaemia after ALG Pretreatment and HL-A Semi-Incompatible Bone Marrow Cell Transfusion

“…A similar beneficial and often more prolonged effect was obtained by the use of allogeneic anti-donor or anti-recipient anti-lymphocyte ser um [17]. The results in our patients follow the rat model [16,17] more closely than the rabbit [8,9]. Despite extensive studies, no definite evi dence of chimaerism could be demonstrated in our patients.…”

“…All were polytransfused with random blood products. In the rabbit with benzene-and 32P-induced AA and in several clinical patients, split and transient haemopoietic engraftments have been achieved after conditioning with ALG followed by mar row infusion [8][9][10][11][12], Despite of histocompatibility differences between donor and recipient, GvH has not been observed. Split chimaerism in the rabbit was of a rather constant pattern; donor erythrocytes, granulocytes and B lymphocytes took while T lymphocytes remained of host type [8,9].…”

“…In the rabbit with benzene-and 32P-induced AA and in several clinical patients, split and transient haemopoietic engraftments have been achieved after conditioning with ALG followed by mar row infusion [8][9][10][11][12], Despite of histocompatibility differences between donor and recipient, GvH has not been observed. Split chimaerism in the rabbit was of a rather constant pattern; donor erythrocytes, granulocytes and B lymphocytes took while T lymphocytes remained of host type [8,9]. In rats rendered aplastic by a lethal dose of cyclophosphamide and treated with rabbit anti-rat lymphocyte serum prior to the infusion of in compatible allogeneic bone marrow, no real takes were achieved [16,17].…”

“…In HL-A-mismatched situations, fatal graft versus host disease (GvH) has always ensued. Conditioning with heterologous anti lymphocyte globulin (ALG) has resulted in split chimaerism in some ex perimental systems [8,9] and in several clinical patients [10][11][12].…”

Results of Immunosuppression in Aplastic Anaemia

“…Speck and Kissling [4, 5]in Basel used experimental rabbit models of benzene- and 32 P-induced marrow aplasia in rabbits, and demonstrated that ALG and mismatched bone marrow could rescue them from aplasia. Subsequent clinical trials in humans showed that the marrow infusion was unnecessary for autologous haematological recovery after ATG therapy [6].…”