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

Abstract

BackgroundAllogeneic 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.Results4 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 MethodsWe 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 × 104 to 1 × 108 CD3+ cells/kg body weight. AYAs were evaluated for response to DLI, graft-versus-host disease (GvHD) and survival.ConclusionsDLI after allo-SCT may control advanced pediatric sarcoma in AYAs with controllable toxicity.

Adoptive cellular immunotherapy for refractory childhood cancers: a single center experience

“…In contrast, clinical expansion of CIK cells with diverse T and NK cell receptor specificities [22] is robust and easy, and therefore once available at our center on August 11, 2011 CIK cell treatment was offered to all consecutive patients. The situation is certainly more clear in a similar paper by Schobrt et al [23] as it focuses on ES and RMS only, treated only with DLI and is thus able to draw the conclusions, that HLA-mismatched DLIs were associated with a trend towards increased survival after allogeneic HSCT and increased post-relapse survival compared to HLA-matched DLI (23 versus 3 months). However, a subdivision of the current paper into the separate disease entities or the different types of ACIs to enable a clearer message due to the low number of patients and the diversity of tumors treated with different conditioning regimens and matched as well as mismatched donors from the statistical point of view was not reasonable.…”

No difference in survival after HLA mismatched versus HLA matched allogeneic stem cell transplantation in Ewing sarcoma patients with advanced disease

“…These results did not exceed the results of standard treatment for patients with the same risk profile [16]. In a further study we demonstrated that unspecific DLIs after allo-SCT are associated with tumor control in AES and stage IV rhabdomyosarcoma patients [17]. This effect is bought with the risk for life-threatening GvHD, emphasizing the need to identify tumor-specific e.g., cellular therapeutic approaches.…”

Precision medicine in pediatric oncology

“…In 1990, Kolb demonstrated in Munich that donor lymphocyte infusions (DLIs) induce remission in chronic myeloid leukemia. DLIs are also effective in several pediatric neoplasias like AML [ 86 ] and advanced pediatric sarcomas [ 87 ]. Allison showed in 1996 for the first time, that blocking inhibitory receptors on tumor-infiltrating T-cells can be therapeutically effective.…”