title: Long-term IL-2 therapy after transplantation of T cell depleted stem cells from alternative donors in children.
abstract: The aim of this pilot study was to evaluate the feasibility of long-term subcutaneous application of low-dose IL-2 in children with malignancies at very high risk of relapse who underwent highly T cell and B cell depleted HLA-identical (MUD) or full haplotype mismatched related hematopoetic stem cell transplantation. We studied 11 patients with acute leukemias / myelodysplastic syndrome and juvenile myelomonocytic leukemia (active disease and/or second stem cell transplantation, n = 8; ≥CR 2, n = 2) and relapsed or progressive Ewing's sarcoma (n = 2) who received prophylactic IL-2 treatment for a high probability of disease recurrence after allo-HSCT. Toxicities from IL-2 were transient fever, fatigue and local inflammation. In one patient GvHD grade III with no clear association to IL-2 administration occurred. IL-2 administration was started at median day 57 (range 13-154) post-transplant for a mean duration of 28 days (range 15-250). IL-2 administration clearly increased NK cell activity. 3 of 11 patients (ALL, AML, multifocal Ewings sarcoma) survived with a follow-up of ten years. In conclusion, long-term low-dose IL-2 subcutaneous application is feasible in children due to a low side effect profile even after HLA mismatched transplantation and may be a strategy to prevent relapse in pediatric malignancies with extremely high risk of relapse.
authors.affiliation: Department of Pediatric Hematology and Oncology, University Children's Hospital Tuebingen, University of Tuebingen, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Schlegel
authors.forename: Heiko-Manuel
authors.initials: HM
authors.lastname: Teltschik
authors.forename: Matthias
authors.initials: M
authors.lastname: Pfeiffer
authors.forename: Rupert
authors.initials: R
authors.lastname: Handgretinger
authors.forename: Michael
authors.initials: M
authors.lastname: Schumm
authors.forename: Ewa
authors.initials: E
authors.lastname: Koscielniak
authors.forename: Tobias
authors.initials: T
authors.lastname: Feuchtinger
authors.forename: Thomas
authors.initials: T
authors.lastname: Klingebiel
authors.forename: Peter
authors.initials: P
authors.lastname: Bader
authors.forename: Paul-Gerhard
authors.initials: PG
authors.lastname: Schlegel
authors.forename: Johann
authors.initials: J
authors.lastname: Greil
authors.forename: Peter
authors.initials: P
authors.lastname: Lang
mesh_terms: D000293:Adolescent; D001402:B-Lymphocytes / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control; D006650:Histocompatibility Testing; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000009:adverse effects; D007694:Killer Cells, Natural / Q000276:immunology; D008212:Lymphocyte Depletion; D008297:Male; D009369:Neoplasms / Q000276:immunology / Q000517:prevention & control*; D012008:Recurrence; D012189:Retrospective Studies; D033581:Stem Cell Transplantation; D013601:T-Lymphocytes; D014184:Transplantation, Homologous
chemical_list: C508594:IL2 protein, human; D007376:Interleukin-2