Targeted bone marrow irradiation in the conditioning of high-risk leukaemia prior to stem cell transplantation

Disease recurrence following stem cell transplantation (SCT) remains a majo r problem. Despite the sensitivity of leukaemias to chemotherapy and irradi ation, conventional conditioning before SCT is limited by significant organ toxicity. Targeted irradiation of bone marrow and spleen by radioimmunothe rapy may provide considerable dose escalation, with limited toxicity to non -target organs. In this study, 27 patients with high-risk or relapsing leuk aemia were treated with rhenium-188-labelled CD66a,b,c,e radioimmunoconjuga tes (Re-188-mAb) specific for normal bone marrow in addition to conventiona l conditioning with high-dose chemotherapy and 12 Gy total body irradiation prior to SCT. A mean activity of 10.2 +/-2.1 (range 6.9-15.8) GBq Re-188-m Ab was administered intravenously. Acute side-effects were assessed accordi ng to the CTC classification and patient outcome was determined. Mean radia tion doses (Gy; range in parentheses) to relevant organs and whole body wer e as follows: 13.1 (6.5-22) to bone marrow, 11.6 (1.7-31.1) to spleen, 5.0 (2.0-11.7) to liver, 7.0 (2.3-11.6) to kidneys, 0.7 (0.3-1.3) to lungs and 1.4 (0.8-2.1) to the whole body. Stem cells engrafted in all patients withi n 9-18 days post SCT. Acute organ toxicity of grade II or less was observed . During follow-up for 25.4 +/-5.3 (range 18-34) months, 4/27 (15%) patient s died from relapse, and 9/27 (33%) from transplantation-related complicati ons. Fourteen patients (52%) are still alive and in ongoing complete clinic al remission. Radioimmunotherapy with the bone marrow-seeking Re-188-labell ed CD66 mAb can double the dose to bone marrow and spleen without undue ext ramedullary acute organ toxicity, when given in addition to high-dose chemo therapy and 12 Gy TBI before allogeneic SCT. This intensified conditioning regimen may reduce the relapse rate of high-risk leukaemia.