Retrospective analysis of consecutive trials from a single center demonstrated that MoAb 3F8 + GM-CSF + CRA is effective against chemotherapy-resistant marrow MRD. Its positive impact on long-term survival can only be confirmed definitively by randomized studies.

Survival outcomes for patients with high-risk neuroblastoma (NB) have significantly improved with anti-disialoganglioside GD2 mAb therapy, which promotes NK cell activation through antibody-dependent cell-mediated cytotoxicity. NK cell activation requires an interaction between inhibitory killer cell immunoglobulin-like receptors (KIRs) and HLA class I ligands. NK cells lacking KIRs that are specific for self HLA are therefore "unlicensed" and hyporesponsive. mAb-treated NB patients lacking HLA class I ligands for their inhibitory KIRs have significantly higher survival rates, suggesting that NK cells expressing KIRs for non-self HLA are mediating tumor control in these individuals. We found that, in the presence of mAb, both licensed and unlicensed NK cells are highly activated in vitro. However, HLA class I expression on NB cell lines selectively inhibited licensed NK cell activity, permitting primarily unlicensed NK cells to mediate antibody-dependent cell-mediated cytotoxicity. These results indicate that unlicensed NK cells play a key antitumor role in patients undergoing mAb therapy via antibody-dependent cell-mediated cytotoxicity, thus explaining the potent "missing KIR ligand" benefit in patients with NB.

Background: In the UK, 8-15% of women suffer from postnatal depression with long term consequences for maternal mood and child development. Current guidelines state that health visitors and GPs should continue to have a major role in the detection and management of postnatal depression. Previous literature suggests that women are reluctant to disclose symptoms of postnatal depression. This study aimed to explore general practitioners' (GPs), health visitors' and women's views on the disclosure of symptoms which may indicate postnatal depression in primary care.

ConclusionOngoing organisational changes within primary care, such as the implementation of corporate working by health visitors, affect care provided to women after birth, which in turn has an impact on the diagnosis and management of postnatal depression.

Anti-GD2 murine antibody 3F8 plus subcutaneously-administered (sc) granulocyte-macrophage colony-stimulating factor (GM-CSF) was used against primary refractory neuroblastoma in metastatic osteomedullary sites. Large study size and long follow-up allowed assessment of prognostic factors in a multivariate analysis not reported with other anti-GD2 antibodies. In a phase II trial, 79 patients without prior progressive disease were treated for persistent osteomedullary neuroblastoma documented by histology and/or metaiodobenzyl-guanidine (MIBG) scan. In the absence of human anti-mouse antibody, 3F8+scGM-CSF cycles were repeated up to 24 months. Minimal residual disease (MRD) in bone marrow was measured by quantitative reverse transcription-polymerase chain reaction pre-enrollment and post-cycle #2, before initiation of 13-cis-retinoic acid. Study endpoints were: 1) progression-free survival (PFS) compared with the predecessor trial of 3F8 plus intravenously-administered (iv) GM-CSF (26 patients), and 2) impact of MRD on PFS. Using all 105 patients from the two consecutive 3F8+GM-CSF trials, prognostic factors were analyzed by multivariate Cox regression model. Complete response rates to 3F8+scGM-CSF were 87% by histology and 38% by MIBG. Five-year PFS was 24%±6% which was significantly superior to 11%±7% with 3F8+ivGM-CSF (p=0.002). In the multivariate analysis, significantly better PFS was associated with R/R or H/R FCGR2A polymorphism, sc route of GM-CSF, and early MRD response. MYCN amplification was not prognostic. Complement consumption was similar with either route of GM-CSF. Toxicities were manageable, allowing outpatient treatment. 3F8+scGM-CSF is highly active against chemoresistant osteomedullary neuroblastoma. MRD response may be an indicator of tumor sensitivity to anti-GD2 immunotherapy. Correlative studies highlight the anti-neoplastic potency of myeloid effectors.