Radioimmunotherapy-based conditioning for hematopoietic cell transplantation in children with malignant and nonmalignant diseases

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Abstract
Targeted irradiation of the bone marrow with radiolabeled monoclonal antibodies (radioimmunotherapy) represents a novel therapeutic approach with both myeloablative and antileukemic potential. In an open-label, single-center pilot study, 30 pediatric and adolescent patients undergoing hematopoietic cell transplantation for malignant (n = 16) and nonmalignant (n = 14) disorders received treatment with a 90Y-labeled anti-CD66 monoclonal antibody. Patients with a high risk of relapse (n = 7) received additional treatment with standard conditioning based on either total body irradiation or busulfan to intensify the antileukemic effect. In patients with comorbidities (n = 23), radioimmunotherapy was combined with a reduced-intensity conditioning regimen to reduce systemic toxicity. Preferential irradiation of the bone marrow was achieved in all patients. Nonrelapse mortality was 4 (13%) of 30 patients. In patients with malignant diseases, the probabilities of overall and disease-free survival at 2 years were 0.69 (95% confidence interval 0.37-0.87) and 0.46 (95% confidence interval 0.19-0.70), respectively. In patients with nonmalignant diseases, the probability of both overall and disease-free survival at 2 years was 0.94 (95% confidence interval 0.63-0.99). This pilot study demonstrates that radioimmunotherapy is effective in achieving myeloablation with low additional toxicity when used in combination with standard or reduced-intensity conditioning in young patients.

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