Long-Term Effects of Allogeneic Hematopoietic Stem Cell Transplantation on Systemic Inflammation in Sickle Cell Disease Patients

Abstract

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only currently available curative treatment for sickle cell disease (SCD). However, the effects of HSCT on SCD pathophysiology are poorly elucidated. Here, we assessed red blood cell (RBC) adhesiveness, intensity of hemolysis, vascular tone markers and systemic inflammation, in SCD patients treated with allogeneic HSCT. Thirty-two SCD patients were evaluated before and on long-term follow-up after HSCT. Overall survival was 94% with no severe (grade III-IV) graft-vs-host disease and a 22% rejection rate (graft failure). Hematological parameters, reticulocyte counts, and levels of lactate dehydrogenase (LDH), endothelin-1 and VCAM-1 normalized in SCD patients post-HSCT. Expression of adhesion molecules on reticulocytes and RBC was lower in patients with sustained engraftment. Levels of IL-18, IL-15 and LDH were higher in patients that developed graft failure. Increased levels of plasma pro-inflammatory cytokines, mainly TNF-α, were found in SCD patients long-term after transplantation. SCD patients with sustained engraftment after allo-HSCT showed decreased reticulocyte counts and adhesiveness, diminished hemolysis, and lower levels of vascular tonus markers. Nevertheless, systemic inflammation persists for at least five years after transplantation, indicating that allo-HSCT does not equally affect all aspects of SCD pathophysiology.

Cerebral hemodynamics and oxygenation in adult patients with sickle cell disease after stem cell transplantation

“…2,3 Hematopoietic stem cell transplantation (HSCT) is currently the only established curative treatment for patients with SCD that results in a lower incidence of VOC events and normalization of hemoglobin levels and markers of hemolysis. 4,5 A common form of brain damage in SCD is the development of silent cerebral infarcts (SCIs), characterized by white matter lesions without corresponding acute clinical symptoms. 6 SCIs are associated with cognitive impairments that can impact an individual's employment opportunities and daily functioning.…”

“…Ischemic brain damage is one of the most devastating complications of SCD that can occur even with hydroxyurea and/or chronic blood transfusions 2,3 . Hematopoietic stem cell transplantation (HSCT) is currently the only established curative treatment for patients with SCD that results in a lower incidence of VOC events and normalization of hemoglobin levels and markers of hemolysis 4,5 …”