Updated project metadata. Even though hematopoietic stem cell transplantation (HSCT) allows successful treatment for many malignant and non-malignant disorders, its curative potential remains limited by severe side effects, including infections and other transplant-related complications such as graft-versus-host disease (GvHD). This study examined changes in serum proteome via high-performance two-dimensional gel electrophoresis (2-DE) during HSCT to search for diagnostic biomarkers for post-HSCT complications. Serum samples were collected from five acute leukaemia patients (n = 5) prior to HSCT (week 0) and weekly after HSCT for eight weeks (week 1–8). A natural cubic spline with a single internal knot at the median HSCT time (t = 21 days after treatment) was fit to each spot’s log-percentage volume contribution (%vol) and 39 spots were determined to be significantly changed due to HSCT.