title: Radioimmunotherapy-based conditioning for hematopoietic cell transplantation in children with malignant and nonmalignant diseases.
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.
authors.affiliation: Department of Pediatrics and Adolescent Medicine, University Hospital Ulm, Ulm, Germany. ansgar.schulz@uniklinik-ulm.de
authors.forename: Ansgar S
authors.initials: AS
authors.lastname: Schulz
authors.forename: Gerhard
authors.initials: G
authors.lastname: Glatting
authors.forename: Manfred
authors.initials: M
authors.lastname: Hoenig
authors.forename: Catharina
authors.initials: C
authors.lastname: Schuetz
authors.forename: Susanne A
authors.initials: SA
authors.lastname: Gatz
authors.forename: Simon
authors.initials: S
authors.lastname: Grewendorf
authors.forename: Monika
authors.initials: M
authors.lastname: Sparber-Sauer
authors.forename: Rainer
authors.initials: R
authors.lastname: Muche
authors.forename: Norbert
authors.initials: N
authors.lastname: Blumstein
authors.forename: Gabriele
authors.initials: G
authors.lastname: Kropshofer
authors.forename: Meinolf
authors.initials: M
authors.lastname: Suttorp
authors.forename: Donald
authors.initials: D
authors.lastname: Bunjes
authors.forename: Klaus-Michael
authors.initials: KM
authors.lastname: Debatin
authors.forename: Sven N
authors.initials: SN
authors.lastname: Reske
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Friedrich
mesh_terms: D000293:Adolescent; D002423:Cause of Death; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease / Q000401:mortality / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D015994:Incidence; D007239:Infections / Q000401:mortality; D053208:Kaplan-Meier Estimate; D007938:Leukemia / Q000401:mortality / Q000628:therapy*; D008297:Male; D009190:Myelodysplastic Syndromes / Q000401:mortality / Q000628:therapy*; D016499:Radioimmunotherapy / Q000379:methods*; D012008:Recurrence; D012307:Risk Factors; D019172:Transplantation Conditioning / Q000379:methods*; D055815:Young Adult