Management of patients with lower-risk myelodysplastic syndromes.

Myelodysplastic syndromes (MDS) are a heterogeneous group of hematopoietic stem cell disorders characterized by ineffective hematopoiesis with abnormal blood cell development (dysplasia) leading to cytopenias and an increased risk for progression to acute myeloid leukemia (AML). Patients with MDS can generally be classified as lower- (LR-MDS) or higher-risk (HR-MDS). As treatment goals for patients with LR-MDS and those with HR-MDS differ significantly, appropriate diagnosis, classification, and follow-up are critical for correct disease management. In this review, we focus on the diagnosis, prognosis, and treatment options, as well as the prediction of the disease course and monitoring of treatment response in patients with LR-MDS. We discuss how next-generation sequencing, increasing knowledge on mechanisms of MDS pathogenesis, and novel therapies may change the current treatment landscape in LR-MDS and why structured assessments of responses, toxicities, and patient-reported outcomes should be incorporated into routine clinical practice

Management of infection prophylaxis in Dutch patients with myelodysplastic syndromes, a web-based case vignette questionnaire:the MINDSET study

OBJECTIVES: Infections are a major cause of morbidity and mortality in patients with myelodysplastic syndromes (MDS). The objective of the MINDSET study was to evaluate haematologists' management of infection prevention in MDS patients using a case vignette study and to assess the availability of guidelines. METHODS: We conducted a web-based, nationwide survey amongst haematologists in the Netherlands between September and December 2021. The survey included a set of case vignettes. Additionally, the availability of protocols was evaluated. RESULTS: Sixty responses were obtained (23.6%). These responses were well distributed across hospital types as well as level of experience. No protocols regarding infection prophylaxis specifically for MDS patients were received. In the case vignette of a 75-year-old MDS patient, respondents would primarily prescribe infection prophylaxis in case of recurrent infections (96.7%) and neutropenia (75.0% for absolute neutrophil count [ANC]<0.2x10^9/L and 53.3% for ANC<0.5x10^9/L), especially in combination with hypomethylating agents (80.0%), lenalidomide (66.7%) or chemotherapy (51.7%). Respondents would predominantly choose antibacterial agents (85.0%), followed by antifungal agents (71.7%). CONCLUSIONS: This study showed diverse reasons and considerations of haematologists regarding whether to prescribe infection prophylaxis in MDS patients. Given the seriousness of infections in MDS patients, patient-tailored recommendations might be valuable in clinical decision-making. This article is protected by copyright. All rights reserved

Tumor immune escape in acute myeloid leukemia: Class II-associated invariant chain peptide expression as result of deficient antigen presentation

In this overview, we discuss the role of class II-associated invariant chain peptide (CLIP) in acute myeloid leukemia (AML), one of the few tumors expressing HLA class II. The clinical impact, function and regulation of CLIP expression on leukemic cells is addressed, indicating its potential as immunotherapeutic target in AML

Computational flow cytometry as a diagnostic tool in suspected-myelodysplastic syndromes

The diagnostic work-up of patients suspected for myelodysplastic syndromes is challenging and mainly relies on bone marrow morphology and cytogenetics. In this study, we developed and prospectively validated a fully computational tool for flow cytometry diagnostics in suspected-MDS. The computational diagnostic workflow consists of methods for pre-processing flow cytometry data, followed by a cell population detection method (FlowSOM) and a machine learning classifier (Random Forest). Based on a six tubes FC panel, the workflow obtained a 90% sensitivity and 93% specificity in an independent validation cohort. For practical advantages (e.g., reduced processing time and costs), a second computational diagnostic workflow was trained, solely based on the best performing single tube of the training cohort. This workflow obtained 97% sensitivity and 95% specificity in the prospective validation cohort. Both workflows outperformed the conventional, expert analyzed flow cytometry scores for diagnosis with respect to accuracy, objectivity and time investment (less than 2 min per patient)

The immunoregulatory role of monocytes and thrombomodulin in myelodysplastic neoplasms

Myelodysplastic neoplasms (MDS) are clonal disorders of the myeloid lineage leading to peripheral blood cytopenias. Dysregulation of innate immunity is hypothesized to be a potent driver of MDS. A recent study revealed increased thrombomodulin (TM) expression on classical monocytes in MDS, which was associated with prolonged survival. TM is a receptor with immunoregulatory capacities, however, its exact role in MDS development remains to be elucidated. In this review we focus on normal monocyte biology and report on the involvement of monocytes in myeloid disease entities with a special focus on MDS. Furthermore, we delve into the current knowledge on TM and its function in monocytes in health and disease and explore the role of TM-expressing monocytes as driver, supporter or epiphenomenon in the MDS bone marrow environment

Increased prescription rate of anti-infective agents after diagnosis of myelodysplastic syndromes

The a priori risk for infections in patients with myelodysplastic syndromes (MDS) is unknown. This study examines prescription rates of anti-infective agents in MDS patients before and after diagnosis, in both in- and outpatient settings, to provide information on infection management in clinical practice. We performed a population-based study using the HemoBase registry, containing data of all MDS patients diagnosed since 2005 in Friesland, the Netherlands. Community and hospital pharmacies provided prescription data from 1995 to 2020. Data were obtained for 203 of 292 patients (70%). Patients received significantly more anti-infective agents, predominantly antibacterials (70%), after diagnosis compared to before: 148.7 defined daily dose/1000 days (DID) (95% CI: 146.9-150.5) and 55.1 DID (95% CI: 54.5-55.8, p < 0.01), respectively, corresponding to median 23.5 and 7.6 treatment days/year. Higher-risk (449.9 DID) and lower-risk patients (129.1 DID) both received significantly more anti-infective agents after diagnosis; comorbidities, neutropenia, and age did not show significant differences relative to prescription rates. Before diagnosis, 10% of patients had infection-related hospital admissions versus 38% after diagnosis. In conclusion, MDS patients received significantly more anti-infective agents compared to before diagnosis. This is the first study that has quantified the prescription rate of anti-infective agents within and beyond the clinical setting in MDS

High INDO (indoleamine 2,3-dioxygenase) mRNA level in blasts of acute myeloid leukemic patients predicts poor clinical outcome

Indoleamine 2,3-dioxygenase degrades the amino acid tryptophan which is essential for T cells. Tryptophan depletion causes T-cell cycle arrest and solid tumors that express high levels of indoleamine 2,3-dioxygenase can create immune suppression. Recently, blasts of patients with acute myeloid leukemia were shown to express indoleamine 2,3-dioxygenase. We determined INDO (encoding gene for indoleamine 2,3-dioxygenase) mRNA expression in leukemic blasts of 286 patients with acute myeloid leukemia by gene-expression profiling. Results were validated by quantitative polymerase chain reaction analysis in blasts of an independent cohort of 71 patients. High INDO expression was correlated to significantly shortened overall and relapse-free survival. Correlation of INDO expression to relevant known prognostic factors and survival identified high INDO expression as a strong negative independent predicting variable for overall and relapse-free survival. Inhibition of indoleamine 2,3-dioxygenase expressed by myeloid leukemic blasts may result in breaking immune tolerance and offers new therapeutic options for patients with acute myeloid leukemia