ALBERT

Description: To examine the effects of short messaging service (SMS) frequency and timing on the efficacy of an SMS-intervention for Hong Kong Chinese adolescents, sixty nine students aged between 12 and 16 (mean age 13.75 ± 0.90) were recruited from five schools in Hong Kong. Participants were randomly assigned into one of five groups: high-frequency + self-selected timing (HST), low-frequency + self-selected timing (LST), high-frequency + assigned timing (HAT), low-frequency + assigned timing (LAT) and the control group. The total duration of the intervention was four weeks. No significant intervention effects were detected in adolescent’s PA among the five groups (F = 1.14, p = 0.346). No significant differences were observed in the stage movement among the five groups (χ2 = 6.18, p = 0.627). No significant differences appeared in the exercise benefits, barriers and benefits/barriers differential scores. However, a growth trend in the exercise benefits score in the LST and HAT groups was found in contrast to the downswing in the control group. The exercise barriers score in the HST group showed the largest reduction after intervention. The benefits/barriers differential score in all the intervention groups increased, whereas it decreased in the control group. Although an increase is demonstrated in the high dosage SMS frequency and timing, no significant intervention effects were found among the five groups in PA behavior, stage of change and exercise benefits and barriers among Hong Kong Chinese adolescents.

Description: Conventional chemotherapeutic regimens for acute myeloid leukemia (AML) patients have demonstrated unsurpassed efficacy in the past decades, but are far from optimal with many patients experiencing multiple disease recurrence or intolerant of the intensive chemotoxicity. Variations in the treatment scheme as well as the use of alternative, targeted agents have been pursued with limited success. This is partly ascribed to the highly heterogeneous nature of the disease comprising a dynamic repertoire of evolving leukemic clones that are both molecularly and biologically diverse, making it difficult to achieve complete disease eradication without inducing adverse off-target effects. In this regard, cellular immunotherapy has emerged as a plausible alternative, leveraging on the diversity and degeneracy of the tumor antigen-recognizing receptor complex expressed by immune cells. In particular, there is a growing interest in the specific anti-leukemia efficacy of the innate-like γδ T cells, prompted by the association of an increased number of donor derived γδ T cells (specifically the Vδ1+ subtype) in allogeneic hematopoietic stem cell transplant (HSCT) patients with improved disease control in the absence of significant graft-versus-host disease (GvHD). We therefore hypothesize that these allogeneic γδ T cells exhibit potent leukemia specific cytotoxicity and serve as an effective treatment for AML. Given the rapid availability and widespread use of cord blood (CB) as an alternative for allogeneic HSCT, we first characterized and explored the potential of expanding CB-derived γδ T cells in vitro. Compared to mobilized peripheral blood (mPB), there is a significantly lower level of γδ T cell within CB mononuclear cells (MCs) (0.61% ± 0.36% in CB vs 4.95% ± 3.83% in mPB, p3.5-fold higher than that in mPB (56.05% ± 9.49% in CB vs 14.54% ± 12.2% in mPB, p90% of the Vδ1+ T cells in CB are of naive or central memory phenotype, more than 40% of these cells in mPB show effector memory expression. We established that optimal in vitro expansion of CB-derived γδ T cells requires direct contact to a mixture of irradiated PBMCs and Epstein-Barr virus-transformed lymphoblastoid cell line (EBV-LCL) at a fixed ratio in the gas-permeable G-Rex culture flask. Under these conditions, we were able to achieve up to 5,200-fold expansion of the starting γδ T cells over a period of 21 days. These cells exhibit potent in vitro cytotoxicity against a range of human AML cell lines, including K562, MOLM-14, MV4-11 and NOMO-1, as well as primary patient samples in a dose dependent manner. In contrast, there is minimal in vitro cytotoxicity against CD34+ cells isolated from allogeneic CB samples even at the highest effector-to-target cell (E:T) ratio tested. Infusion of the expanded γδ T cells into NOD/SCID/IL2Rγ-/- (NSG) mice at 3 weeks post-transplantation of a FLT3-ITD+ AML patient sample (P1) resulted in a significant decrease in leukemic cell engraftment in 40% of the γδ T cells-treated mice (87.46 ± 2.25% in non-treated vs 74.85 ± 1.55% in γδ T cells-treated mice, p=0.022). In a separate experiment, infusion into NSG mouse that was engrafted with low level (0.1%) of a different FLT3-ITD+ AML patient sample (P2) maintained the leukemic cell level low at 0.1% at 4 weeks post-infusion, as opposed to the 〉15-fold increase in leukemic burden (1.76%) seen in the untreated mouse. Consistent with our in vitro finding, infusion of up to 5 x 108 expanded CB derived γδ T cells/kg failed to induce severe GvHD symptoms in NSG mice engrafted with allogeneic human CB cells up to 8 weeks post-infusion, with no significant effect on the level of in vivo regenerated human myeloid and lymphoid cells, as well as colony-forming cells (CFCs). In summary, our data demonstrates that in vitro expanded CB derived γδ T cells show potent AML-specific cytotoxicity both in vitro and in vivo, making it a promising alternative cell source for immunotherapy. Further investigations to enhance the mechanistic understanding would be needed to seed for future clinical translation. Disclosures Hwang: Pfizer: Honoraria, Other: Travel support; MSD: Honoraria, Other: Travel support; BMS: Honoraria, Other: Travel support; Novartis: Honoraria, Other: Travel support; Celgene: Honoraria, Other: Travel support; Roche: Honoraria, Other: Travel support; Janssen: Honoraria, Other: Travel support; Sanofi: Honoraria, Other: Travel support.

Description: We assessed the inter-visit repeatability of 15 × 9-mm2 swept-source OCTA (SS-OCTA; PLEX Elite 9000, Carl Zeiss Meditec) metrics in 14 healthy participants. We analysed the perfusion density (PD) of large vessels, superficial capillary plexus (SCP), and deep capillary plexus (DCP) as well as choriocapillaris flow voids in 2 different regions: the macular region and peripheral region. Also, retinal plexus metrics were processed further using different filters (Hessian, Gabor and Bayesian) while choriocapillaris flow voids were calculated with 1 and 1.25 standard deviation (SD) thresholding algorithms. We found excellent repeatability in the perfusion densities of large vessels (ICC 〉 0.96). Perfusion densities varied with different filters in the macular region (SCP: 24.12–38.57% and DCP: 25.16–38.50%) and peripheral (SCP: 30.52–39.84% and DCP: 34.19–41.60%) regions. The ICCs were lower in the macular region compared to the peripheral region and lower for DCP than for SCP. For choriocapillaris flow voids, the 1.25 SD threshold resulted in fewer flow voids, while a good ICC (ICC 〉 0.81) was achieved using either threshold settings for flow void features in both regions. Our results suggest good repeatability of widefield SS-OCTA for the measurements of retinal perfusion density and choriocapillaris flow voids, but measurements from different filters should not be interchanged.