Real-world experience of CPX-351 as first-line treatment for patients with acute myeloid leukemia.

To investigate the efficacy and toxicities of CPX-351 outside a clinical trial, we analyzed 188 patients (median age 65 years, range 26-80) treated for therapy-related acute myeloid leukemia (t-AML, 29%) or AML with myelodysplasia-related changes (AML-MRC, 70%). Eighty-six percent received one, 14% two induction cycles, and 10% received consolidation (representing 22% of patients with CR/CRi) with CPX-351. Following induction, CR/CRi rate was 47% including 64% of patients with available information achieving measurable residual disease (MRD) negativity (<10-3) as measured by flow cytometry. After a median follow-up of 9.3 months, median overall survival (OS) was 21 months and 1-year OS rate 64%. In multivariate analysis, complex karyotype predicted lower response (p = 0.0001), while pretreatment with hypomethylating agents (p = 0.02) and adverse European LeukemiaNet 2017 genetic risk (p < 0.0001) were associated with lower OS. Allogeneic hematopoietic cell transplantation (allo-HCT) was performed in 116 patients (62%) resulting in promising outcome (median survival not reached, 1-year OS 73%), especially in MRD-negative patients (p = 0.048). With 69% of patients developing grade III/IV non-hematologic toxicity following induction and a day 30-mortality of 8% the safety profile was consistent with previous findings. These real-world data confirm CPX-351 as efficient treatment for these high-risk AML patients facilitating allo-HCT in many patients with promising outcome after transplantation.

Solitary neuroendocrine carcinoma of the heart: a case report.

BACKGROUND: Cardiac tumours are of rare incidence and usually occur in the form of secondary tumours. Most metastatic tumours are melanomas, sarcomas, lung, and haematological malignancies. Neuroendocrine carcinomas (NECs) of the heart are extremely unusual. This case report demonstrates a solitary high-grade NEC of the heart with an individual therapy strategy and follow-up. CASE SUMMARY: A 50-year-old gentleman presented with a 2 days history of recurrent episodes of chest pain. Echocardiography, computed tomography, and magnetic resonance imaging revealed tumorous lesions of the ventricles and aortic valve with large circular pericardial effusion. Histopathology results of the biopsy revealed a poorly differentiated small cell tumour of the neuroendocrine type. Despite further investigations with multiple imaging modalities and laboratory, no primary was found. Chemotherapy was initiated but size progression of the tumour was detected. As no other tumorous lesions were detected and resection was not possible because of the tumour complexity, decision on heart transplantation was made. However, due to the necessary immunosuppression after the heart transplantation, multiple metastasis where discovered in the course of treatment. DISCUSSION: The presence of a NEC in the heart without evidence of any other metastasis or evidence of primary tumour in other organs is clinically unique. For this individual case, heart transplantation was the therapy of choice due to tumour progression under chemotherapy and lacking possibility of resection, as no other suspect lesion was found other than the ones found in the heart. However, the risk of exacerbation of undiscovered micrometastases under necessary immunosuppression following the heart transplantation should be considered.

Synchronous tuberculosis, Epstein-Barr virus-associated lymphoproliferative disorder and cytomegalovirus infection in an allogeneic transplant recipient: a case report.

BACKGROUND: Allogeneic stem cell transplant recipients are prone to infections by various organisms. Tuberculosis (TB) represents a rare infectious complication, especially in countries non-endemic for TB. CASE REPORT: Here, we report the case of a German patient with exposure to TB decades before he was diagnosed with disseminated TB as well as synchronous Epstein-Barr virus associated lymphoproliferative disorder and cytomegalovirus infection after allogeneic stem cell transplantation for refractory acute myeloid leukemia. Tuberculostatic and virostatic therapy was administered and the patient could be discharged with no apparent signs of infection two weeks after initiation of therapy. CONCLUSION: This case illustrates the need for awareness of mycobacterial infections in patients from non-endemic regions undergoing stem cell transplantation even if other reasons for fever are present.

Association of IL-6, hypothalamus-pituitary-adrenal axis function, and depression in patients with cancer.

BACKGROUND: Evidence suggests that cytokines (IL-6) and alteration of the hypothalamic-pituitary-adrenal (HPA) axis play a crucial role in the etiology of depression. Patients with cancer show elevated prevalence rates for depression. The objective of this cross-sectional study was to investigate the associations between these abnormalities and depression. METHODS: Plasma concentrations of IL-6 and cortisol were measured in cancer patients with (N = 31) and without depression (N = 83). The relative diurnal variation of cortisol (cortisol VAR), expressed in percentage, was calculated. RESULTS: There was a significant difference in median plasma concentration of IL-6 between the patients with depression and those without (18.7 vs 2.7 pg/mL; P < .001). Relative cortisol VAR was decreased in depressed patients as compared with patients without depression (11.72% vs 60.6%, P = .037). A positive correlation between the depressive symptoms and IL-6 concentration was found (r = 0.469, P < .001). Negative correlations were found between cortisol VAR versus depressive symptoms and cortisol VAR versus IL-6 (r = -0.6, P < .001 and r = -0.52, P < .001, respectively). IL-6 (odds ratio [OR] = 1.1; 95% confidence interval [CI] = 1.0-1.2; P = .006) and cortisol VAR (OR = 1.3; 95%CI = 1.0-1.4; P = .02) are independently associated with depression. CONCLUSIONS: Depression in cancer is associated with increased plasma IL-6 concentrations and dysfunction of the HPA axis.

Biomarkers of depression in cancer patients.

BACKGROUND: Inflammation and perturbation of the hypothalamic-pituitary-adrenal (HPA) axis function appears to play a putative role in the etiology of depression. Patients with metastatic cancer demonstrate elevated prevalence rates for depression. The objective of the current study was to illustrate the efficacy of interleukin-6 (IL-6) and HPA axis function as adjuncts to support the diagnosis of depression in cancer patients. METHODS: Plasma concentrations of IL-6 and cortisol were measured in 114 cancer patients with and without depression. The relative diurnal variation of cortisol (cortisol VAR), expressed as a percentage, was calculated. Receiver operating characteristics analysis was performed. RESULTS: Depression was associated with increased plasma concentrations of IL-6 (18.7 pg/mL vs. 2.7 pg/mL; P < .001) and higher cortisol concentrations at 8 AM and 8 PM. The relative cortisol VAR (11.7% vs. 60.6%, respectively; P < .001) was found to be decreased in cancer patients with depression, indicating a disturbed circadian function of the HPA axis. As a biomarker of depression, IL-6 yielded at a cutoff value of 10.6 pg/mL, a sensitivity of 79%, and a specificity of 87% (area under the curve [AUC] = 0.86; 95% confidence interval [95% CI], 0.78-0.94), whereas cortisol VAR demonstrated a sensitivity of 81% and a specificity of 88% (AUC = 0.85; 95% CI, 0.74-0.97) at a cutoff value of 33.5%. CONCLUSIONS: Depression is associated with increased plasma IL-6 concentrations in patients with cancer. These patients demonstrate a dysfunction of the HPA-axis, characterized by a decreased diurnal variation of cortisol. The high sensitivity and specificity of these parameters biomarkers of depression make IL-6 and cortisol VAR helpful tools in the diagnosis of depression in patients with cancer.