Regression in cancer following fever and acute infection

Spontaneous regression (SR) in cancer has been an object of interest for a long time. Rare, unexpected and poorly understood regressions from cancer still occur, despite the advances in medicine. In particular, the phenomenon has been observed following fever and acute infections. Based on recent observations in the clinic together with the improved understanding of tumor immunology, we argue that acute infections especially when accompanied by high fever can induce and facilitate an effi cient antitumoral response, and may improve antitumor effi cacy of immunotherapy. We report two cases of remission from cancer observed shortly after an acute, febrile infection: one in the preleucemic condition myelodysplastic syndrome (MDS), later developing to acute myeloid leukemia (AML), and one in metastatic melanoma. The fi rst case was a young female patient who debuted with a week of high fever and signs of an infection. Laboratory results showed pancytopenia and elevated CRP. The patient was treated with broad-spectrum antibiotics whereafter the temperature normalized, but no causative agent of an infection could be detected. A bone marrow biopsy was taken showing hypoplastic conditions despite a clone of larger lymphocytes, but otherwise without convincing signs of malignancy. Less than a month after the admission the blood counts normalized without supply of blood products. Seven months later the patient was readmitted under the same clinical picture with high fever, pancytopenia and elevated CRP. Treatment with broad-spectrum antibiotics was initiated, but yet again, a specifi c infectious agent could not be detected. A new bone marrow biopsy was taken, this time surprisingly with immature blast cells fi lling up to 90% of the marrow, giving the diagnosis of AML. Five days after the second admission the fever resolved and the blood counts improved, being close to normal 25 days after the admission. As the bone marrow was still positive for malignant cells, the standard AML treatment was initiated. Retrospectively, when comparing the latest bone marrow biopsy with the biopsy taken seven months earlier, similar infi ltration of immature, malignant cells could be identifi ed. The count of immature blast cells in the fi rst biopsy, however, was not high enough to meet the criteria of AML, but suggested that the patient initially had suffered from MDS. It seems likely that the patient underwent a complete remission of the MDS, and after relapsing and progressing to AML, experienced a partial remission as the hematological blood counts normalized, but with the bone marrow still being positive for malignant cells. The second case was a previously healthy female patient diagnosed with metastatic melanoma shortly after the operation of a stage III nodular melanoma on her right ankle. Immunotherapy with interleukin 2 (IL2) and interferon-alpha (IFN) was initiated, being our standard treatment for metastatic melanoma. After two cycles of immunotherapy the fi rst evaluation computed tomography (CT)-scan was performed, showing stable disease consisting of unchanged metastatic lymph nodes. The patient had tolerated therapy well with the expected IL-2 related fl u-like symptoms and was therefore recommended two more cycles of immunotherapy. Shortly after the third cycle the patient developed an infection in the area where a central venous catheter had been removed three days before. High fever occurred with Acta Oncologica, 2013; 52: 455–457