Donor lymphocyte infusions in adolescents and young adults for control of advanced pediatric sarcoma
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Sebastian J. Schober1, Irene von Luettichau1, Angela Wawer1, Maximilian Steinhauser1, Christoph Salat2, Wolfgang Schwinger3, Marek Ussowicz4, Petar Antunovic5, Luca Castagna6, Hans-Jochem Kolb1, Stefan E.G. Burdach1,7,* and Uwe Thiel1,*
1Department of Pediatrics and Children’s Cancer Research Center, TUM School of Medicine, Technical University of Munich, Kinderklinik München Schwabing, 80804 Munich, Germany
2Medical Center for Hematology and Oncology Munich MVZ, 80639 Munich, Germany
3Department of Pediatrics, Medical University of Graz, A-8036 Graz, Austria
4Department of Pediatric Oncology, Hematology and Bone Marrow Transplantation, Wroclaw Medical University, 50-368 Wroclaw, Poland
5Department of Hematology and Regional Tumor Registry, University Hospital Linköping, 581 85 Linköping, Sweden
6Department of Oncology and Hematology, IRCCS Humanitas Cancer Center, Humanitas University, 20089, Milan, Italy
7CCC München-Comprehensive Cancer Center, DKTK German Cancer Consortium Munich, 80336 Munich, Germany
*These authors share senior authorship
Sebastian J. Schober, email: [email protected]
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
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 104 to 1 x 108 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.
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