In her dissertation, Marika Lappalainen, MD, evaluated complications of febrile neutropenia in patients, who received intensive chemotherapy for hematological malignancy. Neutropenia is immunodeficient state caused by intensive chemotherapy, which can lead to a life-threatening infection, sepsis. According to the dissertation, the quick-SOFA (qSOFA) score may help to predict complicated course of febrile neutropenia in patients with acute myeloid leukemia (AML).
QSOFA score (sequental sepsis-related organ failure assessment) is a quick tool for evaluating the patient’s clinical condition and need of intensive care. QSOFA score includes three clinical variables: altered mental status, elevated respiratory rate, and low systolic blood pressure. The qSOFA score was assessed retrospectively using patient records in each febrile neutropenia episode after intensive chemotherapy for AML. Elevated qSOFA score of 2 or 3 was strongly associated with sepsis caused by gram-negative bacteria, elevated CRP concentration, and need of ICU treatment.
The use of qSOFA combined with infection biomarkers would help to reduce the delay in recognizing complicated course of febrile neutropenia. However, there is uncertainty in the retrospective evaluation of patient records. Therefore, prospective studies are needed to assess the applicability of qSOFA in the follow-up of febrile neutropenia in AML patients, says Lappalainen.
The dissertation also assessed whether asymmetric dimethylarginine (ADMA) predicts complicated course of febrile neutropenia in hematological patients. ADMA has been observed to predict mortality in intensive care patients. However, in neutropenic patients, the levels of ADMA were similar in patients with and without complicated course of febrile neutropenia. According to these results, ADMA does not predict complicated course of febrile neutropenia in this patient group.
Also metabolomics was used for identifying differences between patients with a complicated versus noncomplicated course of febrile neutropenia. The level of citrulline was lower but the levels of androgen metabolites and phospholipid PE(18:0/20:4) were higher in patients with complicated febrile neutropenia than in patients with non-complicated febrile neutropenia. There is limited experience with the application of metabolomics in this patient population, and understanding the clinical relevance of the findings requires further targeted research.
In conclusion, ADMA did not provide answers to the challenges in the assessment of febrile neutropenia, metabolomics gave some new perspectives concerning potential biomarkers, and qSOFA score underlined the importance of vigorous, continuous clinical evaluation in this patient group.
The study population consisted of patients who received either intensive chemotherapy for acute myeloid leukemia or intensive treatment in conjunction with autologous stem cell transplantation for treatment of multiple myeloma or lymphoma at the adult hematology ward in Kuopio University Hospital. Most patients recovered from febrile neutropenia with supportive care without major problems.
The doctoral dissertation of Marika Lappalainen, MD, entitled "Assessment of febrile neutropenia in hematological patients", will be examined at the Faculty of Health Sciences. The opponent will be Docent Marjatta Sinisalo from Tampere University Hospital and the custos Professor Esa Jantunen from the University of Eastern Finland. The public examination will be held in Finnish online on 22 January 2021 starting at 12 noon.