Assessing Patients’ Knowledge and Attitudes Towards HSCT in an Outpatient-Based Transplant Center in Mexico

Abstract

homing to the GI tract results in decreased GVHD severity and improved outcome in an established humanized mouse model of allo HCT. Methods: Sublethally irradiated RAG2-/-gc-/mice were transplanted with 30 million human PBMCs (huPBMCs). Vedolizumab or control IgG was given intraperitoneally at a dose of 4mg/kg body weight on day-1 and day +15 (preventive approach) or day +8 and day +22 (therapeutic approach). Time points were chosen in order to start a4b7 blockade prior to clinical onset of GVHD (preventive approach) and when animals started to get significantly suffer from GVHD (therapeutic approach). As non-GVHD controls, animals received sublethal irradiation without huPBMCs administration and received VDZ or control IgG to assess for direct conditioning and VDZ toxicity. Results: HuPBMC CD45 splenocyte analysis on day +28 after infusion demonstrated strong human leukocyte engraftment with more than 80% of spleen cells being huCD45 positive. Both preventive and therapeutic administration of Vedolizumab resulted in significantly improved survival in HuPBMC treated recipients when compared to IgG treated GVHD controls at week 8 (62.6% Vs 12.5% and 50% Vs 12.5% respectively). All recipients, which did not receive huPBMCs survived, indicating VDZ safety in this model. Clinical GVHD scores after day 21 after transplant were significantly lower in VDZ huPBMCs treated animals until end of analysis compared to control-treated recipients using both the preventive and therapeutic approaches, along with significant decreases in GI tract pathology scores on day +28. No differences in pathology were seen in liver or lung at this time point. Serum cytokine analysis revealed decreases in TNF (p<0.05) and IFNg (p<0.05) levels in Vedolizumab therapeutically treated recipients on day +28 and in TNF (p<0.05) in preventively treated recipients compared to control treated animals. Histopathologic analysis of T cell infiltration of small intestine and colon by immunohistochemistry for CD3 antibody revealed significantly lower infiltration of human T cells in VDZ huPBMCs treated group (p<0.05). Conclusion: Vedolizumab reduces the severity of intestinal GVHD by targeting donor T cell migration into the intestinal tract both when given early prior to onset of clinical disease and given at later time point, and improves overall survival both in the preventive and therapeutic setting. Given these promising results, targeting T cell homing with VDZ potentially presents a novel option for the management of intestinal GVHD.