The impact of kidney function on survival in elderly patients diagnosed with acute myeloid leukemia.

BACKGROUND: Acute myeloid leukemia (AML) is an aggressive hematological cancer that involves myeloid cells. Elderly patients with comorbidities and poor performance status (PS) receive treatment with hypomethylating agents or supportive care. Several models are available to predict treatment-related mortality and they all primarily focus on PS. Little is known about the impact of chronic kidney disease (CKD) on survival in elderly patients with AML. MATERIALS AND METHODS: We performed a retrospective analysis of 81 patients (51.9% male) aged over 65 years when the diagnosis of AML was established. The median observation period lasted 108 days (IQR 292, maximum 1,169). Patients' documentation was examined for previous illnesses, PS was calculated, basic laboratory blood tests and a bone marrow biopsy were done. CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m2. RESULTS: The median age of patients was 75 years (IQR 14, maximum 93). The mean eGFR was 59.5 ± 24.0 mL/min/1.73m2. CKD was present in almost half of patients (49.4%). Altogether, 69 (85.2%) patients died during the observation period. Kaplan-Meier survival analysis showed statistically lower survival for CKD patients (log-rank χ2 = 6.736; p = 0.009). Cox regression model, adjusted for age, comorbidities, and treatment, revealed the main predictors for patient survival to be PS, AML type, and blast percentage. CONCLUSION: Our results indicate that elderly patients with AML have worse survival when diagnosed with CKD, however CKD was not one of the main predictors of patient survival.

Increased Frequency of Circulating Activated FOXP3+ Regulatory T Cell Subset in Patients with Chronic Lymphocytic Leukemia Is Associated with the Estimate of the Size of the Tumor Mass, STAT5 Signaling and Disease Course during Follow-Up of Patients on Therapy.

INTRODUCTION: Advanced chronic lymphocytic leukemia (CLL) is accompanied by increased circulating regulatory T cells (Tregs) and increased susceptibility to severe infections, which were also shown to entail a striking induction of FOXP3 expression in Tregs. As homeostasis of the most suppressive CD45RA-FOXP3high activated Treg (aTreg) subset differs, it is critical to analyse homeostatic signalling in Treg subsets. MATERIALS AND METHODS: In this study, by using conventional and imaging flow cytometry, we monitored STAT5 signalling/phosphorylation (pSTAT5) and investigated Treg subsets in relation to the Binet stage, the total tumor mass score (TTM) and the disease course during a follow-up of 37 patients with CLL. RESULTS: The aTreg percentage was significantly increased among CD4+ T cells from patients with advanced disease and significantly correlated with the TTM. A subgroup of patients with higher aTreg percentages among CD4+FOXP3+ T cells at the start of therapy was characterised by more frequent episodes of severe infections during follow-up. CONCLUSIONS: The results suggesting that an aTreg fraction could represent a possible marker of a severe disease course with infectious complications. Augmented homeostatic STAT5 signalling could support aTreg expansion, as higher pSTAT5 levels were significantly correlated with an increased aTreg frequency among CD4+FOXP3+ T cells during the follow-up of patients on therapy, as well as following SARS-CoV-2 antigen-specific stimulation in vitro.

New Flow Cytometric Methods for Monitoring STAT5 Signaling Reveal Responses to SARS-CoV-2 Antigen-Specific Stimulation in FOXP3+ Regulatory T Cells also in Patients with Advanced Chronic Lymphocytic Leukemia.

Increased frequency of CD4+CD25+ regulatory T-cells (Treg) has been associated with disease progression in chronic lymphocytic leukemia (CLL). Flow cytometric methods, which allow for the simultaneous analysis of their specific transcription factor Foxp3 and activated STAT proteins, together with proliferation can help to elucidate the signaling mechanisms driving Treg expansion and suppression of FOXP3- conventional CD4+T-cells (Tcon). Herein, we first report a novel approach in which STAT5 phosphorylation (pSTAT5) and proliferation (BrdU-FITC incorporation) could be analyzed specifically in FOXP3+ and FOXP3- responding cells after CD3/CD28 stimulation. The addition of magnetically purified CD4+CD25+ T-cells from healthy donors to cocultured autologous CD4+CD25- T-cells resulted in suppression of Tcon cell cycle progression accompanied by a decrease in pSTAT5. Next, a method using imaging flow cytometry is presented for the detection of cytokine-dependent pSTAT5 nuclear translocation in FOXP3-expressing cells. Finally, we discuss our experimental data obtained by combining Treg pSTAT5 analysis and antigen-specific stimulation with SARS-CoV-2 antigens. Applying these methods on samples from patients revealed Treg responses to antigen-specific stimulation and significantly higher basal pSTAT5 in CLL patients treated with immunochemotherapy. Thus, we speculate that through the use of this pharmacodynamic tool, the efficacy of immunosuppressive drugs and their possible off-target effects can be assessed.

Cystic dystrophy of the duodenal wall in a heterotopic pancreas.

Cystic dystrophy of the duodenal wall in heterotopic pancreas is a rare disease affecting younger men in particular. On account of its difficult diagnosis and nonspecific signs, it was first described in 1970. A 51-year-old male patient was admitted for clarification of several months of severe pain in the upper abdomen accompanied by weight-loss, and due to ultrasonically established suspicion of carcinoma in the head of the pancreas. Clinical examination and laboratory tests were nonsignificant. Barium meal and esophagogastroduodenoscopy revealed a severe deformation of the duodenum. Biopsy of the duodenal mucosa detected moderate inflammatory changes. Ultrasound examination showed cystic changes in the duodenal wall and in the vicinity of the head of the pancreas. Only with the aid of endoscopic ultrasound, could bizarre cystic changes in the submucosa of the duodenal wall be detected, which was also confirmed by computer tomography. The signs of disease are nonspecific. Duodenal biopsy also does not reveal its cause since the typical lesions lie deeper in the submucosa or muscularis propria. Cystic changes with fibrosis, pancreatic ducts and lobi without anatomic or vascular connection to the pancreas are found. The anomaly involves, above all, the stomach and duodenum. Prior to the introduction of imaging techniques such as endoscopic ultrasonography, computer tomography and nuclear magnetic resonance, the diagnosis could only be made by means of an operative procedure. Treatment is primarily surgical; smaller cysts can be treated by endoscopic fenestration. Pharmacological treatment with somatostatin is rarely performed.