Haploidentical Stem Cell Transplantation in Neuroblastoma

High-dose MIBG With Subsequent Transplantation of Haploidentical Stem Cells in Children With Therapy Resistant Neuroblastoma

Children with primary resistant or relapsed neuroblastoma who do not achieve remission with conventional chemotherapy have extremely dismal prognosis. A novel treatment strategy combining tumor targeted radioisotope treatment with metaiodobenzylguanidine (MIBG) and immunotherapeutic effect of haploidentical stem cell transplantation (haploSCT) followed by low-dose donor lymphocyte infusions will be piloted. The use of the isotope is aimed to decrease pre-transplant tumour burden. Reduced intensity conditioning containing Fludarabine, Thiotepa and Melfalan will enable sustained engraftment as well as will serve as additional anti-tumor treatment. A prompt natural killer (NK)-cell mediated tumour control may be achieved by haploidentical stem cell transplantation. The investigators hypothesize that tumour cells potentially evading NK-cell mediated immunity may be targeted by infused donor T-cells and eliminated by either MHC-dependent manner or through a bystander effect. The possible graft versus tumor effect will be evaluated in children with therapy resistant neuroblastoma.

Inclusion Criteria:

• Refractory neuroblastoma (any chemo/radiosensitive stable disease)
• Relapse incl. autologous HSCT 3 m earlier
• Primary induction failure
• Cardiac output SF ≥25%
• Creatinine clearance ≥40 cc/min/1.73 m2
• Performance score of ≥50% (Lansky or Karnofsky)
• Available haploidentical family donor, aged ≥18 yrs, HIV-neg

Exclusion Criteria:

• Rapidly progressive disease
• Pregnancy