Local immune cell infiltration in cutaneous acute graft versus host disease

Abstract

Background Hematopoietic stem cell transplant is a crucial intervention to definitively treat many hematopoietic malignancies, but it carries great risks of morbidity and mortality often associated with graft-versus-host disease (GVHD). Acute and chronic GVHD are distinct entities, defined by a combination of historical, clinical, and pathologic data, but both are generally thought to stem from self-propagating aberrantly activated immune cells inflicting end organ damage, with the potential to cause significant illness or even death. Event-free survival rates after hematopoietic stem cell transplant continue to improve each year, but GVHD remains a major hurdle in improving the efficacy and safety of transplant. Objective Recent studies demonstrating tissue-specific immune effector phenotypes underscore the need for a deeper understanding of the cellular and molecular pathways driving the destruction of target tissues in patients with acute GVHD. Methods Samples were collected from lesional and unaffected skin in five patients with acute cutaneous GHVD. Fresh tissue was processed for fluorescence-activated cell sorting and analysis of macrophages and lymphocytes. Results The percentage of lymphocytes and macrophages as a representation of total cells varied among patients and was not always consistent between lesional and unaffected sites. The heterogeneity in immune cell profiling observed in patients in this study could reflect the diverse demographics, conditioning, and transplant conditions of each individual. Conclusion This study provides initial insight into the underlying molecular mechanisms of cutaneous GVHD progression and paves the way for additional studies to examine the cellular and molecular landscape in greater detail.

Treosulfan is a safe and effective alternative to busulfan for conditioning in adult allogeneic HSCT patients: Data from a single center

“…The post-inflammatory state which occurs after the damage caused by busulfan within the early post-transplant period may set a scene for the establishment of chronic skin GVHD. [23][24][25] Chronic GVHD prevalence was found to be similar in a recent meta-analysis that compared treosulfan and busulfan based regimens in patients with AML/ MDS. 21 As usage of treosulfan became more common with the research in recent years, we implemented a strategy that prioritized treosulfan usage in our clinic.…”

“…Chronic GVHD was encountered more frequently in the busulfan group (32.1% vs. 15.7%) and this difference was most prominently observed in the skin GVHD subtype. The post‐inflammatory state which occurs after the damage caused by busulfan within the early post‐transplant period may set a scene for the establishment of chronic skin GVHD 23–25 . Chronic GVHD prevalence was found to be similar in a recent meta‐analysis that compared treosulfan and busulfan based regimens in patients with AML/MDS 21 .…”