(1) Glycoproteins account for ~80% of proteins located at the cell surface and in the extracellular matrix. A growing body of evidence indicates that α-L-fucose protein modifications contribute to breast cancer progression and metastatic disease. (2) Using a combination of techniques, including matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) based in cell and on tissue imaging and glycan sequencing using exoglycosidase analysis coupled to hydrophilic interaction ultra-high performance liquid chromatography (HILIC UPLC), we establish that a core-fucosylated tetra-antennary glycan containing a single N-acetyllactosamine (F(6)A4G4Lac1) is associated with poor clinical outcomes in breast cancer, including lymph node metastasis, recurrent disease, and reduced survival. (3) This study is the first to identify a single N-glycan, F(6)A4G4Lac1, as having a correlation with poor clinical outcomes in breast cancer.

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Long-term outcomes after allogeneic hematopoietic cell transplantation (HCT) for therapy-related myeloid neoplasms (tMNs) are dismal. There are few multicenter studies defining prognostic factors in pediatric patients with tMNs. We have accumulated the largest cohort of pediatric patients who have undergone HCT for a tMN to perform a multivariate analysis defining factors predictive of long-term survival.Sixty-eight percent of the 401 patients underwent HCT using a myeloablative conditioning (MAC) regimen, but there were no statistically significant differences in the overall survival (OS), event-free survival (EFS), or cumulative incidence of relapse and non-relapse mortality based on the conditioning intensity. Among the recipients of MAC regimens, 38.4% of deaths were from treatment-related causes, especially acute graft versus host disease (GVHD) and end organ failure, as compared to only 20.9% of deaths in the reduced intensity conditioning (RIC) cohort. Exposure to total body irradiation (TBI) during conditioning and experiencing grade III/IV acute GVHD were associated with worse OS. In addition, a diagnosis of therapy related myelodysplastic syndrome and having a structurally complex karyotype at tMN diagnosis were associated with worse EFS.Reduced-toxicity (but not reduced-intensity) regimens might help to decrease relapse while limiting mortality associated with TBI-based HCT conditioning in pediatric patients with tMNs.

graft-versus-host disease (GvHD) symptoms following the administration of rimiducid. Aims: Evaluate the safety and efficacy of BPX-501 in pediatric pts with malignant or non-malignant disorders. Primary endpoint is event-free survival (EFS) at 180 days [events include transplant related mortality (TRM) (or NRM [non-relapse related mortality] for malignant patients), severe GVHD (acute Grade 2-4 organ or extensive chronic GVHD) and life-threatening infections]. Methods: This multicenter EU (NCT02065869), prospective trial utilizes ab-T and B-cell-depleted haplo-HSCT followed by infusion of donor lymphocytes with iC9. BPX-501 was planned to be infused on day14 §4 after the allograft with no post-transplant GvHD prophylaxis allowed. Pts developing steroid-resistant GvHD could receive 1 dose of rimiducid activating iC9. Results: As of June 30, 2018, 166 pts (described in Table 1) were efficacy evaluable. Median time for neutrophil and platelet engraftment was 16 and 11 days, respectively. No pts experienced graft failure. Three pts (1.8%) developed Grade III-IV aGvHD. Of 132 evaluable pts, 9 (7.2%) developed cGvHD with 2 experiencing moderate À severe cGvHD. Eleven pts received rimiducid; 10 pts had at least 1 post administration response assessment. The best overall response rate (CR/PR) was 100% with 9 pts (90%) achieving CR. EFS was 92.7%. At a median f/u of 17.6 mos, 5 pts (3.3%) experienced TRM. DFS and OS were 89.4% and 94.2%, respectively. By day 100, CD3 + and CD3 + CD4 + T cells above were > 500 cells/ml were achieved by day 100. IgA and IgM levels achieved normal values by day 180. Conclusion: Preliminary efficacy outcomes demonstrate a highly effective transplantation strategy for pediatric pts with malignant or non-malignant disorders. Overall rates of GvHD were low with few cases of high-grade GvHD. Rimiducid was an effective treatment for pts with steroidrefractory GvHD.