TRANSPLANTATION OF SYNGENEIC BONE MARROW INCUBATED WITH LEUKOCYTE ANTIBODIES

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Abstract
Bone marrow removed from leukemic patients during remission, for retransplantation during relapse, may contain residual leukemic cells. Antisera against surface antigens of these cells should not react with hemopoietic stem cells. In order to produce an appropriate antiserum, rabbits were given injections of cells from the common form of acute lymphoblastic leukemia (cALL) of childhood. The resultant antiserum was absorbed with liver-kidney homogenate, chronic lymphoid leukemia cells (CLL), normal peripheral lymphocytes, and lymphoblastoid cells from B cell lines. The purified globulin fraction showed high complement-dependent cytotoxicity against the cells of 39 of 56 patients with ALL. It did not react with the cells of 11 T-ALL, 1 B-ALL, and 5 undifferentiated (without known markers) ALL. Furthermore, the antiserum did not react with the cells from acute myeloid leukemias, chronic lymphoid leukemias, B-type lymphoblastoid cell lines, normal bone marrow cells, and peripheral blood lymphocytes. Unabsorbed anti-cALL globulin was found to be highly cytotoxic against hemopoietic colony-forming cells (CFU-c) and completely inhibited the growth of marrow cells and CFU-c in diffusion chambers. Absorption of anti-cALL with liver-kidney homogenate, CLL, and peripheral blood lymphocytes removed only part of the cytotoxic antibodies cross-reacting with antigens present on CFU-c. An additional absorption with lymphoblastoid cell lines removed the cytotoxic effect of anti-cALL against CFU-c completely and did not inhibit proliferation of marrow cells and CFU-c in diffusion chambers, while high cytotoxicity against cALL blasts was preserved. It follows that cALL antiserum lacks an inhibitory effect on normal hemopoietic stem cells when measured in CFU-c and diffusion chamber assays. The nonreactivity of cALL antiserum against hemopoietic stem cells would be a prerequisite for a therapeutic use of the antiserum in “antileukemic auto transplantation”. This is an approach to eliminate by antibodies against cell surface antigens residual leukemic cells in the bone marrow taken during remission and stored for retransplantation in relapse. Its principle was tested in a previous study on mice, where anti-T cell globulin was shown to eradicate leukemic cells without inhibiting stem cells required for bone marrow transplantation (25). In this study the question was raised whether anti-cALL made specific against common ALL (27), affects normal hemopoietic stem or precursor cells. The inhibition of colony-forming cells was used to test for a possible cytotoxic or inhibitory effect of the antiserum (18). This system was applied along with the diffusion chamber technique as an indicator for stem cell function.