Donor lymphocyte infusions in adolescents and young adults for control of advanced pediatric sarcoma

// Sebastian J. Schober 1 , Irene von Luettichau 1 , Angela Wawer 1 , Maximilian Steinhauser 1 , Christoph Salat 2 , Wolfgang Schwinger 3 , Marek Ussowicz 4 , Petar Antunovic 5 , Luca Castagna 6 , Hans-Jochem Kolb 1 , Stefan E.G. Burdach 1, 7, * and Uwe Thiel 1, * 1 Department of Pediatrics and Children’s Cancer Research Center, TUM School of Medicine, Technical University of Munich, Kinderklinik Munchen Schwabing, 80804 Munich, Germany 2 Medical Center for Hematology and Oncology Munich MVZ, 80639 Munich, Germany 3 Department of Pediatrics, Medical University of Graz, A-8036 Graz, Austria 4 Department of Pediatric Oncology, Hematology and Bone Marrow Transplantation, Wroclaw Medical University, 50-368 Wroclaw, Poland 5 Department of Hematology and Regional Tumor Registry, University Hospital Linkoping, 581 85 Linkoping, Sweden 6 Department of Oncology and Hematology, IRCCS Humanitas Cancer Center, Humanitas University, 20089, Milan, Italy 7 CCC Munchen-Comprehensive Cancer Center, DKTK German Cancer Consortium Munich, 80336 Munich, Germany * These authors share senior authorship Correspondence to: Sebastian J. Schober, email: sebastianjohannes.schober@tum.de Keywords: donor lymphocyte infusion; allogeneic stem cell transplantation; Ewing sarcoma; rhabdomyosarcoma; alloimmunity and transplantation Received: January 19, 2018      Accepted: April 06, 2018      Published: April 27, 2018 ABSTRACT Background: Allogeneic stem cell transplantation (allo-SCT) and donor lymphocyte infusions (DLI) may induce a graft-versus-tumor effect in pediatric sarcoma patients. Here, we describe general feasibility, toxicity and efficacy of DLI after allo-SCT. Results: 4 of 8 patients responded. ES#4 had stable disease (SD) for 9 months after DLI and RMS#4 partial response for 8 months with combined hyperthermia/chemotherapy. In ES#4, DLI led to SD for 6 months and reverted residual disease before allo-SCT into complete remission. After DLI, ES#4 and RMS#4 developed acute GvHD (°III–°IV), ES#4 also developed chronic GvHD. 5 patients including ES#4 lived longer than expected. Median survival after allo-SCT was 2.3 years, post-relapse survival (PRS) was 13 months. Off note, HLA-mismatched DLI were associated with a trend towards increased survival after allo-SCT and increased PRS compared to HLA-matched DLI (23 versus 3 months). Materials and Methods: We studied eight adolescents and young adults (AYAs) with advanced Ewing sarcoma (ES#1-4) and rhabdomyosarcoma (RMS#1-4) who received DLI. Escalating doses ranged from 2.5 x 10 4 to 1 x 10 8 CD3 + cells/kg body weight. AYAs were evaluated for response to DLI, graft-versus-host disease (GvHD) and survival. Conclusions: DLI after allo-SCT may control advanced pediatric sarcoma in AYAs with controllable toxicity.