Prospective Evaluation Of Proteomic Pattern Specific For aGvHD In More Than 300 Patients

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative treatment for many hematologic malignancies or hematopoietic dysfunction syndromes in adult patients, but the application is still limited due to major complications, such as severe graft versus host disease (GvHD) and/or infectious complications. Diagnosis of aGvHD is based on clinical features and biopsies, a non invasive, unbiased laboratory test was developed earlier and has been evaluated prospectively and blinded on more than 1290 samples collected from more than 327 patients undergoing allo-HSCT at Hannover Medical School (MHH) and 7 additional clinics. The majority of the patients included was transplanted for hematological malignancies (n=320), 9 for hematopoietic failure syndromes, mainly severe aplastic anemia. Conditioning regimens included reduced intensity conditioning regimens (RIC) for about 60% of the patients of MHH, as well as standard conditioning regimens (mainly TBI+Cy or Busulfan+Cy). GvHD-prophylaxis was cyclosporine A (CSA) and mycophenolate (MMF) or CSA metothrexate (MTX), as appropriate. In addition, about 80% percent of the patients received ATG (antithymocyte globulin) prior to HSCT. A peptide pattern of 31 peptides – either absent/decreased (15) or present/increased (16) – was previously published (Weissinger et al. 2007), a new pattern MS_17 was developed and prospectively evaluated in parallel for the last 2 years. Prospective and blinded evaluation of the patients included in this analysis for early recognition of patients at risk for aGvHD development revealed the correct classification of patients developing aGvHD about 7 days prior to the development of clinical symptoms for aGVHD with a sensitivity 76% and specificity of about 85%. Additional data on the efficacy of a pilot study for pre-emptive therapy driven by pattern positivity yielded encouraging results on incidence and severity of aGvHD will be reported. Based on these data a pre-emptive therapy multicenter trial, administering steroids upon positivity of the proteomic pattern has been initiated now in 10 German centers, testing the efficacy of the pre-emptive therapy on incidence and severity of aGvHD and a possible benefit on overall survival of the patients.