Graft viability and transfusion related complications in patients undergoing stem cell transplantation

Abstract

Allogeneic hematopoietic stem cell transplantation (HSCT) is a treatment strategy for patients with hematopoietic malignancies and inborn errors of metabolism or immunodeficiencies. A successful clinical outcome depends on many factors, such as underlying disease, the patients’ status, treatment protocol, donor, graft source and occurrence and severity of complications such as graft versus host disease (GVHD) and infections. The scope of this thesis is to achieve greater understanding of clinical effects and immunological mechanisms of blood group differences and cellular transfusion in patients undergoing HSCT. In addition we investigate the impact of cell graft quality.

HSCT can be performed across the ABO blood group barrier but the impact of blood group incompatibility in HSCT is debated. In scientific paper I we analyzed the impact of blood group differences on graft failure (GF). This is a retrospective single center study including 224 patients who underwent myeloablative allogeneic HSCT with grafts from an unrelated donor in 1997-2003. Graft failure (GF) was seen in 6 patients (2.7%). Major ABO mismatch and HLA allele mismatch was significantly associated with GF in the multivariate analysis. In scientific paper II we retrospectively analyzed 310 patients receiving reduced intensity conditioning (RIC) HSCT in 1998-2011. We found no influence of ABO mismatch on overall clinical outcome. However, patients with an ABO mismatched graft required more blood transfusions. We then investigated antibody related complications post-HSCT. Autoimmune hemolytic anemia did not affect overall survival (OS) or transplant related mortality (TRM). Patients with ABO related antibody complications post-HSCT had inferior OS and more TRM. These studies imply that the role of ABO mismatches is not obvious. However, other factors of greater impact may override the effect of ABO donor-recipient differences thus obfuscating its influence.

In scientific paper III we retrospectively investigated the impact of HSCT grafts with inferior quality on clinical outcome in 144 patients receiving peripheral blood stem cell grafts. Graft quality was measured as viability of a frozen/thawed control sample. Patients who received grafts with inferior quality developed acute GVHD more frequently and had higher TRM. Grafts with white blood cell count >300 x109/L had lower viability. In conclusion, graft quality influence clinical outcome after HSCT, hence, conditions for graft storage and handling need to be optimized.

In patients that develop mucositis or breakthrough infections after HSCT, granulocyte transfusions (GCX) can be used. Scientific paper IV addresses GCX treatment in 85 patients between 1998 and 2014. GCX can be obtained from donors pretreated with steroids only (S-GCX) or steroids and G-CSF (GCSF-GCX). The overall response to GCX treatment was similar between S-GCX and GCSF-GCX but more complete responses were observed in the GCSF-GCX group. Patients who received GCX due to mucositis benefitted most from GCX whereas the effects of GCX in patients treated due to infection was not as clear. Adverse events (AE) were reported in 36 cases of which 6 were life-threatening or fatal pulmonary AEs. All severe AEs reported were seen in patients treated due to severe infection, further complicating the decision to use GCX treatment in these patients.