186Rhenium-labeled anti-CD20 antibody radioimmunotherapy followed by autologous peripheral blood stem cell transplantation in patients with relapsed or refractory non-Hodgkin lymphoma.

186 Rhenium-labeled anti-CD20 antibody radioimmunotherapy followed by autologous peripheral blood stem cell transplantation in patients with relapsed or refractory non-Hodgkin lymphoma We read with interest the article of Gopal et al 1 on the use of high-dose radioimmunotherapy in relapsed follicular lymphoma. Here, we report on our experience using a rhenium 186 (186 Re)– radiolabeled chimeric anti-CD20 antibody (rituximab). We chose 186 Re as treatment isotope because of its favorable physical properties (3.7 d half-life; 1070 keV ␤-energy; 9.5% 137 keV ␥-radiation). The ␥-radiation enables intratherapeutic imaging and dosimetry. Furthermore, a stable antibody-labeling technique had been developed for both 186 Re and 99 metastable (99m) technetium (99m Tc). 2,3 186 Re was generated by neutron irradiation of 185 Re in the high-flux position of the University of Missouri Research Reactor. We treated 4 patients with refractory or relapsed diffuse large B-cell lymphoma (DLBCL; n ϭ 2), mantle cell lymphoma (MCL; n ϭ 1), and follicular lymphoma (n ϭ 1) (Table 1). To determine antibody uptake in the tumor and to measure blood kinetics, an imaging study with 1.5 to 2 GBq 99m Tc-labeled antibody (10-20 mg) was performed. The blood radioactivity curve was fitted biexponentially. While the initial decrease reflected spleen uptake, the second phase matched early kinetics and distribution if predosing was applied as done for treatment. Dose of radioactivity for treatment in order to obtain a blood dose of 25 Gy (n ϭ 3) and 30 Gy (n ϭ 1), respectively, was calculated from the blood kinetics of the test application and the physical half-life of 186 Re. Total antibody dose was 3 mg/kg. A dose of 1.5 to 2 mg was given unlabeled one hour before the Re-antibody infusion. The patients received a total blood dose of 24 to 26 Gy (n ϭ 3) and 38 Gy (n ϭ 1). When residual bone marrow dose was less than 0.3 Gy, the patients' stem cells (2.92 ϫ 10 6 CD34 ϩ cells/kg body weight [range, 1.78-4.42 ϫ 10 6 CD34 ϩ cells/kg body weight]) were reinfused (d 8-13 after treatment). All patients experienced myeloablation. Time to neutrophil counts of at least 0.5 ϫ 10 9 /L was 10 days (range, 9-11 days) after transplantation, and time to platelet counts of at least 25 ϫ 10 9 /L was 12 days (range, 11-14 days) after transplantation. Neutropenia lasted 17 days (range, 11-22 days) and thrombocytopenia 16.5 days (range, 10-24 …