This study investigated the effect of metronomic cyclophosphamide (CPA) in combination with personalized peptide vaccination (PPV) on regulatory T cells (Treg) and myeloid-derived suppressor cells (MDSC), and whether it could improve the antitumor effect of PPV. Seventy patients with metastatic castration-resistant prostate cancer were randomly assigned (1:1) to receive PPV plus oral low-dose CPA (50 mg/day), or PPV alone. PPV treatment used a maximum of four peptides chosen from 31 pooled peptides according to human leukocyte antigen types and antigen-specific humoral immune responses before PPV, for 8 subcutaneous weekly injections. Peptide-specific cytotoxic T lymphocyte (CTL) and immunoglobulin G responses were measured before and after PPV. The incidence of grade 3 or 4 hematologic adverse events was higher in the PPV plus CPA arm than in the PPV alone arm. Decrease in Treg and increase in MDSC were more pronounced in PPV plus CPA treatment than in PPV alone (p = 0.036 and p = 0.048, respectively). There was no correlation between the changes in Treg or MDSC and CTL response. There was no difference in positive immune responses between the two arms, although overall survival in patients with positive immune responses was longer than in those with negative immune responses (p = 0.001). Significant differences in neither progression-free survival nor overall survival were observed between the two arms. Low-dose CPA showed no change in the antitumor effect of PPV, possibly due to the simultaneous decrease in Treg and increase in MDSC, in patients under PPV.
Triple-color flow cytometric analysis using CD81/CD56/CD45 MoAbs is useful for detecting NBL cells in PB. Further studies testing this approach using samples of PB with NBL contamination are needed to test this approach in patients.
We report a patient with congenital dyserythropoietic anemia type 1 with characteristic anomalies and two novel clinicopathologic presentations: intrauterine onset of severe anemia resulting in cardiac failure and relatively mild dyserythropoietic features on bone marrow aspiration in contrast to severity of anemia. After repeated transfusions and a trial of erythropoietin administration, the patient died from respiratory infection at age 7 months. Autopsy revealed characteristic dyserythropoietic features of the bone marrow by light microscopy and electron microscopy, which confirmed a diagnosis of congenital dyserythropoietic anemia type 1.
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