153Sm EDTMP for bone marrow ablation prior to stem cell transplantation for haematological malignancies

This study examined the safety of adding 153Sm lexidronam to standard conditioning regimens in patients undergoing stem cell transplantation for marrow based haematological malignancies in whom total-body irradiation as part of conditioning was desirable but not feasible. Ten such patients were enrolled, seven with multiple myeloma. An escalating regimen of 19-45 GBq of 153Sm lexidronam was added 12-14 days prior to the standard transplantation regimen. Evaluation parameters included time to engraftment, status at day +100 by International Bone Marrow Transplant Registry (IBMTR) criteria and toxicity during this period. Absorbed marrow radiation doses were estimated using the MIRDOSE 3 program. No adverse events were attributable to 153Sm lexidronam. Of the seven patients with multiple myeloma, four achieved complete response, two partial response, and another had stable monoclonal band at 3 months post-transplant. One patient with Refractory Anaemic with Excess Blasts in transformation (RAEBt) died of a presumed fungal infection, whilst another with acute myeloid leukaemia relapsed, dying at day +153. A patient with low-grade lymphoma showed no evidence of residual disease at day +100. The total marrow absorbed dose was estimated to be 0.7+/-0.2 mGy x MBq(-1). Regional uptake was markedly non-uniform with poor uptake in the appendicular skeleton. Dose-limiting toxicity was not attained. At the activities used 153Sm lexidronam was not associated with additional toxicity in this population. Adequate absorbed radiation dose to appendicular marrow is unlikely to be deliverable by this approach alone.