Radioimmunotherapy for Myeloablation Before SCT in Paediatric Patients with Malignant and Non-Malignant Diseases.

Radioimmunotherapy (RIT) using radio-labelled monoclonal antibodies can be used for targeted radiation of the bone marrow in the context of SCT. We explored this treatment in 32 pediatric patients with malignant and non-malignant bone marrow disorders with very high risk patterns from disease or comorbidity. For RIT the Yttrium-90 labelled anti-CD66 (n=30) or anti-CD45 (n=2) monoclonal antibodies were used. Dosimetry was performed about 3 weeks before SCT and showed favourable organ distribution. RIT was administered on an outpatient basis 12 to 15 days before SCT. The mean BM dose was 27 Gy (range 11–46) in malignant diseases and 17 Gy (range 16–20) in non-malignant diseases. Patient characteristics were as follows:

1. malignant diseases (n=16): 7 ALL, 8 AML, 1 Neuroblastoma °IV; disease status pre-BMT: 7 CR2, 2 CR>2, 7 PR/NR;

2. non-malignant diseases (n=16): 12 immunologic disorders (SCID, CID, Hyper-IgM-Syndrome, Hyper-IgE-Syndrome, CGD-Syndrome, Griscelli-Syndrome, IFN-γ-Receptor-Deficiency.), 4 hematologic disorders (Thalassemia major, congenital haemolytic anaemia).

Additional risk factors were active aspergillosis (n=4), acute pneumonia (n=5), liver fibrosis (n=4) and previous transplant (n=7). RIT was followed by high dose conditioning (based on TBI or high dose Busulfan) in 9 malignant cases or by reduced intensity conditioning (based on Fludarabin ± Melphalan) in 7 malignant and all non-malignant cases. Donors were HLA-genoidentical (n=10), matched unrelated (n=15), mismatched related (n=1), mismatched unrelated (n=2) or HLA-haploidentical relatives (n=4). RIT was well tolerated in all patients and no sign of significant additional or unexpected toxicity was observed. Myeloablation was achieved in all patients. All but 2 patients, who rejected their HLA-haploidentical grafts, showed a primary engraftment within the normal time frame after SCT. Six patients died, 3 from TRM and 3 from relapse. Eleven out of 16 patients with malignant diseases survive 3–53 months (median 26 months), 15 out of 16 patients with non-malignant diseases survive 3–30 months (median 11 months). Interestingly, all but one of the 23 patients treated by RIT and reduced intensity chemo-conditioning survive (1 y estimated survival 0.9, 95% CI 0.51–0.99). Taken together, targeted immunotherapy is a promising approach for myeloablation in pediatric patients with high comorbidity and/or high relapse risk.