Discussion
The results of the current early phase II study showed that pre-vaccination IgG levels against 31 peptide vaccine candidates in patients with relapsed childhood cancer were suppressed when compared with the URI group. This immunosuppression could be partly owing to adverse effects associated with repeated intensive treatments for relapsed childhood cancer. However, these suppressed immunological features were not only cancelled but rather strongly boosted by administering the PPV. This finding should be confirmed in a large-scale PPV study of childhood cancer with age-matched controls.
We treated only four patients using the PPV; hence, it is impossible to discuss or evaluate the clinical benefits of the PPV for childhood cancer. However, these findings might be useful for better designing the next step of the trial. Only one patient achieved long-term remission. The other three cases showed disease progression, regardless of the enhancement in the level of IgG antibodies to the vaccinated peptides in cases 2 and 3. Therefore, patients in remission, but not those with active metastatic tumors, might be more appropriate as candidates for PPV therapy.
Regarding case 1 that was successfully treated with the PPV, rhabdomyosarcoma is the most common soft tissue sarcoma in children, comprising 3.5% of cases among children aged 0–14 years.13 A higher relapse rate (up to 50%) was one of the features of ARMS.14-16 Furthermore, patients with ARMS with metastasis, similar to the patient reported herein, were reported to have dismal OS.17,18 The results of the current study suggest that the PPV has some consolidation effect on childhood solid tumors when the tumor is controlled at the time of entry, in agreement with the results of the effects of the WT1 peptide vaccination in five cases.19 Collectively, these results help in planning the next step of the phase II study of the PPV considering the immune boosting effect and safety.
Conflicts of interest : Itoh K received research funding from the Taiho Pharmaceutical Company. The remaining authors have nothing to declare.
Funding: The present study did not receive specific funding, but was performed as part of the Kurume University, Kurume Fukuoka, Japan, and in part by Sendai Kousei Hospital, Sendai, Japan
Acknowledgment : We thank Drs. Shigeki Shichijo, and Yasushi Ohtsu for their contribution in supporting the clinical study. We thank Junko Umezaki for supporting the patients and families as a responsible research nurse. We also appreciate all the patients with pediatric cancer and their families as well as all the children with infectious diseases of the respiratory tract.