title: Favorable NK cell activity after haploidentical hematopoietic stem cell transplantation in stage IV relapsed Ewing's sarcoma patients.
abstract: Natural killer (NK) cell activity has been shown to have potential activity against Ewing's sarcoma (EWS) especially in tumors with low HLA I expression and high NKG2D expression. Two patients with metastatic relapsed and primary metastatic stage IV EWS who had received two courses of high dose chemotherapy with autologous stem cell rescue were transplanted from a haploidentical parental stem cell donor. Patients are alive in ongoing CR for 10.2 and 3.4 years now. Post transplant local second and first relapses were treated successfully in both patients. In vivo IL-2 stimulation not only increased the number and activity of effector cells in one patient but was also associated with severe GvHD. In vitro studies demonstrated high NK cell activity against K562 and relevant activity against EWS cell line A673 post transplant. NK activity was enhanced by cytokine prestimulation as well as by EWS targeting anti-GD2 Ab. Haploidentical hematopoietic stem cell transplantation (HSCT) might contribute to long-term survival by NK cell-mediated effect exerted by donor-derived NK cells. Local tumor recurrence was manageable in both high-risk patients indicating systemic immune control preventing subsequent metastasizing. The efficacy of haploidentical HSCT, cytokine application and tumor targeting antibodies for the use of Ab-dependent cellular cytotoxicity needs evaluation in clinical trials.
authors.affiliation: Department of Pediatric Hematology and Oncology, University Children's Hospital, Eberhard Karl's University, Tübingen, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Schlegel
authors.affiliation: Department of Pediatric Hematology and Oncology, University Children's Hospital, Eberhard Karl's University, Tübingen, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Feuchtinger
authors.affiliation: Department of Pediatric Hematology and Oncology, University Children's Hospital, Eberhard Karl's University, Tübingen, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Nitschke-Gérard
authors.affiliation: Department of Pediatric Hematology and Oncology, University Children's Hospital, Eberhard Karl's University, Tübingen, Germany.
authors.forename: U J Eva
authors.initials: UJ
authors.lastname: Seidel
authors.affiliation: Department of Pediatric Hematology and Oncology, University Children's Hospital, Eberhard Karl's University, Tübingen, Germany.
authors.forename: A-M
authors.initials: AM
authors.lastname: Lang
authors.affiliation: Department of Pediatric Hematology and Oncology, University Children's Hospital, Eberhard Karl's University, Tübingen, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Kyzirakos
authors.affiliation: Department of Pediatric Hematology and Oncology, University Children's Hospital, Eberhard Karl's University, Tübingen, Germany.
authors.forename: H-M
authors.initials: HM
authors.lastname: Teltschik
authors.affiliation: Department of Pediatric Hematology and Oncology, University Children's Hospital, Eberhard Karl's University, Tübingen, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Ebinger
authors.affiliation: Department of Pediatric Hematology and Oncology, University Children's Hospital, Eberhard Karl's University, Tübingen, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Schumm
authors.affiliation: Department of Pediatric Hematology and Oncology, Olgahospital Children's Hospital, Stuttgart, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Koscielniak
authors.affiliation: Department of Pediatric Hematology and Oncology, University Children's Hospital, Eberhard Karl's University, Tübingen, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Handgretinger
authors.affiliation: Department of Pediatric Hematology and Oncology, University Children's Hospital, Eberhard Karl's University, Tübingen, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Lang
mesh_terms: D000293:Adolescent; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000276:immunology; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D009367:Neoplasm Staging; D012512:Sarcoma, Ewing / Q000276:immunology / Q000473:pathology / Q000517:prevention & control
chemical_list: C527085:KLRK1 protein, human; D055655:NK Cell Lectin-Like Receptor Subfamily K