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

Abstract

Prognosis of refractory childhood cancers despite multimodal treatment strategies remains poor. Here, we report a single center experience encountered in 18 patients with refractory solid malignancies treated with adoptive cellular immunotherapy (ACI) from haploidentical or matched donors following hematopoietic stem cell transplantation. While seven patients were in partial and six in complete remission (CR), five patients suffered from relapsed diseases at the time of ACI. 1.5-year probabilities of overall survival (OS) and progression-free survival (PFS) were 19.5% and 16.1% for all patients. Patients in CR showed estimated 1.5-year OS and PFS of 50.1% and 42.7%, respectively. CR was induced or rather sustained in ten children, with two still being alive 9.6 and 9.3 years after ACI. Naïve, central and effector memory T-cells correlated with responses. However, the majority of patients relapsed. Cumulative incidence of relapse was 79.8% at 1.5 years. Acute graft versus host disease (aGVHD) occurred in nine of 18 patients (50%) with aGVHD grade I–II observed in six (33%) and aGVHD grade III seen in three (17%) patients, manageable in all cases.Altogether, study results indicate that donor-derived ACI at its current state offers palliation but no clear curative benefit for refractory childhood cancers and warrants further improvement.

No Improvement of Survival for Alveolar Rhabdomyosarcoma Patients After HLA-Matched Versus -Mismatched Allogeneic Hematopoietic Stem Cell Transplantation Compared to Standard-of-Care Therapy

“…In the present study, incidence of acute and chronic GvHD was comparable to other studies published for RMS ( 15 , 22 , 23 ) or EwS ( 18 ). Notably, TRM in our analysis (0.20) is higher than described for RMS by Merker et al.…”

ERBB2-CAR-Engineered Cytokine-Induced Killer Cells Exhibit Both CAR-Mediated and Innate Immunity Against High-Risk Rhabdomyosarcoma

“…However, especially in advanced disease, tumors escape immunosurveillance by cancer immunoediting and an immunosuppressive tumor microenvironment (TME). Despite improvements in surgical and radiotherapy techniques, new chemotherapy regimens, and the use of allogeneic stem cell transplantation, children, and young adults with metastatic alveolar rhabdomyosarcoma (RMS)-except those younger than 10 years of age-still succumb to their disease within a median of 2 years (1)(2)(3)(4)(5)(6)(7)(8). Thus, all treatment advances made over the last three decades have not translated into improved outcomes in high-risk RMS patients.…”