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.