The thermodynamic stability of biofluids is currently extensively studied by means of differential scanning calorimetry (DSC), a biophysical technique that measures thermally induced conformational transitions of biomolecules in solution. In this work we utilize the calorimetric approach to monitor myeloma patients after autologous stem cell transplantation. The thermodynamic parameters determined from the calorimetric profiles of blood sera collected before and at different periods of time after the transplantation were compared with the variation in the levels of the secreted paraproteins, monoclonal free light chains and involved heavy/light chains searching for correlations between the calorimetric markers and the immunological indicators of prognosis prediction and monitoring response. We established that the change in the paraprotein level and thus the patient's clinical status is clearly reflected in the serum thermogram. Our study proves the potential of micro-calorimetry as a non-invasive tool for patients' monitoring after autologous stem cell transplantation.