Non-Genetic Factors which Influence HSCT Outcome

Outcomes for Haemopoietic Stem Cell Transplantation (HCST) are improving with improvements in conditioning regimes and GvHD prophylaxis and treatment. Potential outcomes for HSCT include Overall Survival (OS), Leukemia Free Survival (LFS), Rejection, Relapse, Non-Engraftment, GvHD, Infection and Transplant Related Mortality (TRM). These outcomes result from multiple inputs including genetic and non-genetic factors all of which influence donor selection.

The non-genetic factors which can influence HSCT outcomes and therefore donor selection include patient, donor and transplant related factors.

Donor components include donor age, gender and virology status (including donor CMV status). Of these, studies have demonstrated that the most important is donor age. Transplants using donors aged 18-35 fair best, followed by those using donors aged 35 – 45. Transplants using donors older than 45 have the worst outcome. HSCTs that use male donors do best from a GvHD point of view compared to those that use female donors. HSCT using female donors into male patients is associated with higher GvHD rates. However, HSCTs involving male donors into female patients are associated with higher rejection rates. Donor CMV matching to patient CMV is important for avoiding CMV transmission or patient CMV reactivation.

Patient factors which influence HSCT outcomes include disease stage, patient age, gender and virology status (including CMV status). Of these, the single most important patient factor is disease stage. For malignant diseases, patients transplanted early have the best outcomes, followed by patients with intermediate stage disease. Patients transplanted with advanced disease have the worst outcome. The influence of patient gender on HSCT outcomes are as described for donor factors. i.e. HSCTs using female donors into male patients are associated with higher GvHD rates whilst those involving male donors into female patients are associated with higher rejection rates. In terms of age, younger patients have a significantly better outcome than older patients. As with donor factors, donor CMV matching to patient CMV is important for avoiding CMV transmission or patient CMV reactivation.

Transplant factors which influence HSCT outcomes include conditioning regimes, GvHD prophylaxis and treatment as well as infection control regimes. The use of less toxic conditioning regimes, particularly reduced intensity regime (RIC) have allowed older patients in particular to benefit from HSCT and have improved overall patient survival.