Myeloablative radioimmunotherapy with Re-188-anti-CD66-antibody for conditioning of high-risk leukemia patients prior to stem cell transplantation: biodistribution, biokinetics and immediate toxicities

BACKGROUND: Stem cell transplantation (SCT) is potentially curative for high-risk leukemia patients. Conditioning regimens affect relapse rate and treatment-related mortality. We evaluated biodistribution, radiation absorbed organ doses and immediate toxicities of myeloablative radioimmunotherapy with marrow selective 188rhenium (188Re)-labeled anti-CD66 monoclonal antibody (mAb).

METHODS: Fifty high-risk leukemia patients were treated 14 +/- 2 days prior to SCT. Dosimetric measurements were performed at 1.5, 3, 20, 26, and 44 hours after about 1 GBq of 188Re followed by radioimmunotherapy with about 10 GBq 188Re. Standard conditioning consisted of high-dose chemotherapy and 12 Gy total-body irradiation. Forty-six patients received allogenic, and four received autologous, stem cell grafts.

RESULTS: The mean radiation absorbed doses (in Gy) were: marrow, 13.9 +/- 4.6; liver, 5.7 +/- 2.7; spleen, 22.6 +/- 25.5; kidneys, 6.8 +/- 2.6; lungs, 0.8 +/- 0.7; total body, 1.4 +/- 0.3. The tumor-to-organ-ratios were 2.4 for liver, 0.6 for the spleen, 2.0 for the kidneys and 17.8 for the lungs. Type of leukemia did not affect radiation absorbed doses of marrow, lungs, kidneys and liver. Mean marrow dose of transplanted patients in complete remission was 1.37 +/- 0.43 Gy/GBq, compared with 1.34 +/- 0.29 Gy/GBq for patients with leukemic blast marrow infiltration of 5-25%. Immediate side effects were moderate. All patients showed primary engraftment. After a median follow-up of 11.0 +/- 7.4 months 28/50 patients (56%) are in ongoing complete remission. Nine patients (5%) have relapsed, seven (4%) of them have died. Another 13 patients (7%) died of treatment-related causes.

CONCLUSIONS: Due to its biodistribution, radiation absorbed organ doses, low toxicity and clinical data, myeloablative radioimmunotherapy with 188Re-labeled anti-CD66 mAb seems to be a promising method for improving standard conditioning of high-risk leukemia patients prior to SCT.