153Sm-EDTMP and melphalan chemoradiotherapy regimen for bone marrow ablation prior to marrow transplantation: an experimental model in the rat

Chemoradiotherapy with melphalan and 153Sm-ethylenediaminetetramethylene phosphonate (EDTMP) was used to ablate bone marrow in WAG rats which were subsequently rescued by marrow transplantation. Internal irradiation of bone marrow with high doses of up to 3.5 GBq kg-1 153Sm-EDTMP alone produced profound, but self-limiting, myelosuppression and all animals recovered spontaneously. Melphalan alone in doses of 9.5 mg kg-1 also caused transient myelosuppression without mortality. However, the combination of 9.5 mg kg-1 melphalan and 555 MBq kg-1 153Sm-EDTMP caused marrow ablation and death in 80% of animals. The mortality of this chemoradiotherapy regimen was reduced to 7% by sequential administration of 153Sm-EDTMP on day 0 and melphalan on day 5 followed by marrow transfusion of 7.5 x 10(7) cells on day 6. These results were comparable to those obtained following bone marrow transplantation 24 h after lethal total body external beam irradiation. In the inbred WAG rat experimental model the sequential chemoradiotherapeutic regimen of internal irradiation with 153Sm-EDTMP followed by chemotherapy with melphalan was demonstrated to ablate bone marrow effectively whilst preserving the capacity for recovery following marrow transplantation.