Precision Medicine for Stem Cell Transplantation

Development of biomarkers that predict the onset of acute graft-versus-host disease (aGvHD)

GvHD staging in this study is based on the approach of Harris et al., (2016). The weekly aGvHD assessments will provide the clinical data necessary to establish the confidence of diagnosis, severity at onset, peak severity and outcome. Four weeks of follow-up will determine whether patients achieve a complete response (CR) or very good partial response (VGPR) by day 28. In addition, the 6-month assessment will identify patients who died as a result of aGvHD and those who are alive and off immunosuppression at six months. These validated clinical endpoints will be used to identify biomarker signatures that predict aGvHD severity and response to therapy. Calendar-driven assessments will also be used to identify patients given topical steroids for grade I aGvHD as these patients may need to be excluded from use as negative controls or included as edge cases in future validation studies.

Development of biomarkers that predict the relapse of acute myeloid leukaemia.

Relapse remains the leading cause of death for most transplant recipients. Approximately 40% of AML patients suffer disease recurrence, with a median time to relapse of 7 months. The 6-month follow-up assessment will therefore identify many cases of early relapse. The study will remain open for 3 years after the last assessment to allow regular updating of clinical outcome data to identify later cases of relapse. These data and the accompanying clinical samples will be used to identify cytomic and proteomic signatures of immune dysfunction and AML relapse and provide an invaluable resource for studying mechanisms of disease recurrence.