4-hydroperoxycyclophosphamide: a model for eliminating residual human tumour cells and T-lymphocytes from the bone...

Autologous bone marrow transplantation in acute leukaemia carries the risk of relapse from reinfusion of tumour cells present in marrow collected in remission and cryopreserved. An effective method for clearing marrow of tumour cells is required for a successful outcome. In the animal model 4-hydroperoxycyclophosphamide (4-HC) has proved to be effective in eliminating tumour cells from an autologous marrow graft. In the present studies, the in vitro effect of short- and long-term marrow cell incubation with 4-HC on haemopoietic stem cells was investigated to determine the maximum concentration of 4-HC that can be used for in vitro incubation without destroying the capacity of the marrow to effect complete haematological recovery as judged by residual CFUc content. However, loss of CFUc may not necessarily parallel survival of pluripotential stem cells. 4-HC was also shown to be effective against peripheral T-lymphocytes. Its possible therapeutic use in preventing or ameliorating graft-versus-host disease in allogeneic marrow grafts by preincubation with 4-HC prior to transplantation is discussed.