Lenalidomide as immune adjuvant to a dendritic cell vaccine in chronic lymphocytic leukemia patients.

OBJECTIVES: We previously showed that immunization with ex vivo- generated autologous dendritic cells loaded with apoptotic tumor cells (Apo-DC) potentiated tumor-specific immunity in chronic lymphocytic leukemia (CLL) patients. Here, we evaluated safety and immunogenicity of Apo-DC in combination with lenalidomide, granulocyte-macrophage colony-stimulating factor (GM-CSF), and low-dose cyclophosphamide (CTX). METHODS: Ten previously untreated patients with slowly progressing CLL received 5 Apo-DC vaccinations and lenalidomide orally for 24 weeks either alone (cohort I, n = 5) or together with subcutaneous GM-CSF and intravenous CTX (cohort II, n = 5). Tumor-specific T-cell responses were measured by proliferation and IFN-γ ELISPOT assays. Immune monitoring was performed by flow cytometry. RESULTS: Dose-limiting toxicity was observed in 3/10 patients, 2 in cohort I and one in cohort II. One patient developed autoimmune hemolytic anemia and another grade 4 thrombocytopenia. Vaccine-induced immune responses were seen in 5/5 and 4/5 patients in cohort I and II, respectively. The expression of immune checkpoints on T cells did not change significantly. CONCLUSIONS: Lenalidomide alone or in combination with GM-CSF and low-dose CTX as immune adjuvant to the Apo-DC vaccine elicited tumor-specific T-cell responses in CLL patients. However, unexpected toxicity was observed and caution is suggested in further exploring this drug as immune adjuvant in CLL.

Self-perception of symptoms of anemia and fatigue before and after blood transfusions in patients with myelodysplastic syndromes.

PURPOSE: Myelodysplastic syndromes (MDS) constitute a heterogeneous group of clonal bone marrow disorders characterized by chronic refractory anemia. Many patients with MDS are dependent on regular blood transfusions. The study aimed to investigate symptoms of anemia and fatigue in patients with MDS immediately before and after blood transfusion and to capture patients' descriptions of their symptoms. METHODS: Sixteen transfusion-dependent MDS patients with a median age of 74 years (range 67-91) were included. Data were collected longitudinally using the Functional Assessment of Cancer Therapy Anemia (FACT-An) questionnaire, which measured anemia and fatigue symptoms before and after one blood transfusion (day 0-4 and 7). In addition, each patient was interviewed about his or her symptoms. RESULTS: The median total score on FACT-An increased after blood transfusion from 50 to 58 (day 0-7, p = 0.016), indicating decreased symptom burden. A positive correlation was found between increments in the FACT-An score and hemoglobin value (rs 0.66, p = 0.02). One of seven items measuring symptoms of anemia (shortness of breath) and two of 13 symptoms of fatigue (feeling fatigue and weakness) changed significantly for the better from day 0 to day 7. The interviews confirmed the FACT-An results and revealed that patients experienced severe fatigue that negatively affected the maintenance of interpersonal relationships. CONCLUSIONS: After blood transfusion, symptoms of anemia and fatigue decreased in patients with MDS. The patients felt their symptoms had a negative impact on social life. Providing psychosocial support may contribute to improve the care of patients with transfusion-dependent MDS.