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.
Highlights
Prognosis of pediatric patients with intermediateor even high-risk sarcomas such as rhabdomyosarcoma (RMS) synovial sarcoma (SS), or Ewing sarcoma (ES) as well as with neuroblastoma (NB), hepatoblastoma (HBL) or nasopharyngeal carcinoma (NPC) has improved dramatically over the last decades by first line treatments [1,2,3,4,5].adolescents and young adults with metastatic alveolar subtype RMS including bone or bone marrow involvement still are incurable [6]
More than one third of the remaining patients enrolled in this study had achieved complete remission (CR) before hematopoietic stem cell transplantation (HSCT) (7 of 17, 41%), while another seven of 17 (41%) patients had obtained at least very good partial or partial response (VGPR or partial remission (PR)), and three patients (18%) suffered from relapsed or refractory diseases at the time of transplantation
There is no clear and convincing evidence yet to support allogeneic HSCT, and the role for donor-derived adoptive cellular immunotherapy (ACI) in children and adolescents suffering from these cancers
Summary
Prognosis of pediatric patients with intermediateor even high-risk sarcomas such as rhabdomyosarcoma (RMS) synovial sarcoma (SS), or Ewing sarcoma (ES) as well as with neuroblastoma (NB), hepatoblastoma (HBL) or nasopharyngeal carcinoma (NPC) has improved dramatically over the last decades by first line treatments [1,2,3,4,5].adolescents and young adults with metastatic alveolar subtype RMS including bone or bone marrow involvement still are incurable [6]. Prognosis of pediatric patients with intermediateor even high-risk sarcomas such as rhabdomyosarcoma (RMS) synovial sarcoma (SS), or Ewing sarcoma (ES) as well as with neuroblastoma (NB), hepatoblastoma (HBL) or nasopharyngeal carcinoma (NPC) has improved dramatically over the last decades by first line treatments [1,2,3,4,5]. More than half of high-risk patients (International Neuroblastoma Staging System (INSS) stage 4 and INRG stage M patients ≥18 months of age and all NB-patients with a MYCN amplification) die from disease despite intensive multimodal treatment, including chemotherapy, surgery and myeloablative chemotherapy with autologous stem cell www.oncotarget.com rescue, as well as 131-metaiodobenzylguanidine therapy or external beam radiation. The combination of the ch14.18/ SP2/0 anti-GD2 antibody (Dinutuximab), CSF2 (colony stimulating factor 2), interleukin (IL)-2 and isotretinoin may be provided in case of refractory disease [9]
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