Classification, risk stratification and response assessment in myelodysplastic syndromes/neoplasms (MDS): A state-of-the-art report on behalf of the International Consortium for MDS (icMDS).

The guidelines for classification, prognostication, and response assessment of myelodysplastic syndromes/neoplasms (MDS) have all recently been updated. In this report on behalf of the International Consortium for MDS (icMDS) we summarize these developments. We first critically examine the updated World Health Organization (WHO) classification and the International Consensus Classification (ICC) of MDS. We then compare traditional and molecularly based risk MDS risk assessment tools. Lastly, we discuss limitations of criteria in measuring therapeutic benefit and highlight how the International Working Group (IWG) 2018 and 2023 response criteria addressed these deficiencies and are endorsed by the icMDS. We also address the importance of patient centered care by discussing the value of quality-of-life assessment. We hope that the reader of this review will have a better understanding of how to classify MDS, predict clinical outcomes and evaluate therapeutic outcomes.

Special considerations in the management of adult patients with acute leukaemias and myeloid neoplasms in the COVID-19 era: recommendations from a panel of international experts.

The ongoing COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 is a global public health crisis. Multiple observations indicate poorer post-infection outcomes for patients with cancer than for the general population. Herein, we highlight the challenges in caring for patients with acute leukaemias and myeloid neoplasms amid the COVID-19 pandemic. We summarise key changes related to service allocation, clinical and supportive care, clinical trial participation, and ethical considerations regarding the use of lifesaving measures for these patients. We recognise that these recommendations might be more applicable to high-income countries and might not be generalisable because of regional differences in health-care infrastructure, individual circumstances, and a complex and highly fluid health-care environment. Despite these limitations, we aim to provide a general framework for the care of patients with acute leukaemias and myeloid neoplasms during the COVID-19 pandemic on the basis of recommendations from international experts.

The National MDS Natural History Study: design of an integrated data and sample biorepository to promote research studies in myelodysplastic syndromes.

Myelodysplastic syndromes (MDS), a spectrum of heterogeneous hematopoietic stem cell diseases, vary in clinical severity, response to therapy, and propensity toward progression to acute myeloid leukemia. These are acquired clonal disorders resulting from somatic mutations within the hematopoietic stem or progenitor cell population. Understanding the natural history and the risk of developing leukemia and other adverse outcomes is dependent on access to well-annotated biospecimens linked to robust clinical and molecular data. To facilitate the acquisition and distribution of MDS biospecimens to the wider scientific community and support scientific discovery in this disease, the National MDS Natural History study was initiated by the National Heart, Lung, and Blood Institute (NHLBI) and is being conducted in collaboration with community hospitals and academic medical centers supported by the National Cancer Institute (NCI). The study will recruit up to 2000 MDS patients or overlapping myeloproliferative neoplasms (MDS/MPN) and up to 500 cases of idiopathic cytopenia of undetermined significance (ICUS). The National MDS Natural History Study (NCT02775383) will offer the world's largest disease-focused tissue biobank linked to longitudinal clinical and molecular data in MDS. Here, we report on the study design features and describe the vanguard phase of 200 cases. The study assembles a comprehensive clinical database, quality of life results, laboratory data, histopathology slides and images, genetic information, hematopoietic and germline tissues representing high-quality biospecimens and data from diverse centers across the United States. These resources will be available to the scientific community for investigator-initiated research.

Patterns of treatment and costs associated with transfusion burden in patients with myelodysplastic syndromes.

Transfusion dependence (TD) among myelodysplastic syndromes (MDS) patients negatively impacts survival and health-related quality of life. We evaluated cost patterns of MDS care during TD and transfusion independence (TI). MDS patients were identified from a US claims database (2008-2013). TD was defined as ≥2 consecutive 8-week periods with ≥1 claim during each, and no interim 56-day period without transfusion; TI as 8 subsequent transfusion-free weeks; and transfusion frequency as the mean interval between transfusions during the TD period. 13,741 patients were included; 19% were TD and 70% had a mean interval between transfusions of ≤28 days. During a 2-year period, TD patients incurred a mean total cost of $17,815/patient-month; 53% higher for those with ≤28 days ($19,498) vs. >28 days ($12,717) between transfusions. Among patients who achieved TI, mean total cost was $7874/patient-month. For TD-MDS patients, cost increases are proportional to transfusion frequency and achieving TI yields economic benefits.

Nine years without a new FDA-approved therapy for MDS: how can we break through the impasse?

The myelodysplastic syndromes (MDSs) are a heterogeneous collection of clonal hematopoietic malignancies that compromise a large subgroup of the myeloid neoplasms and collectively are the most common acquired adult bone marrow failure syndromes. Currently, only 3 agents are approved for the treatment of MDS by the US Food and Drug Administration (FDA): azacitidine, decitabine, and lenalidomide. The latter drug, approved in 2006, is the most recent agent approved by the FDA for MDS and there has been mediocre success with novel agents for the past 9 years. The heterogeneity of MDS as a disease group is likely to be a strong contributor to this slow progress but recent developments in molecular characterization of MDS are improving diagnostic accuracy, providing insights into pathogenesis and refining our prognostic ability in the field. With the advent of these developments, appropriately chosen therapeutics or even targeted agents may be able to improve patient outcomes in the future.

Myelodysplastic syndromes, version 2.2015.

The NCCN Guidelines for Myelodysplastic Syndromes (MDS) comprise a heterogeneous group of myeloid disorders with a highly variable disease course that depends largely on risk factors. Risk evaluation is therefore a critical component of decision-making in the treatment of MDS. The development of newer treatments and the refinement of current treatment modalities are designed to improve patient outcomes and reduce side effects. These NCCN Guidelines Insights focus on the recent updates to the guidelines, which include the incorporation of a revised prognostic scoring system, addition of molecular abnormalities associated with MDS, and refinement of treatment options involving a discussion of cost of care.

Risk-adjusted clinical outcomes in patients enrolled in a bloodless program.

BACKGROUND: Although clinical outcomes have been reported for patients who do not accept allogeneic blood transfusion (ABT), many previous studies lack a control group, fail to use risk adjustment, and focus exclusively on cardiac surgery. STUDY DESIGN AND METHODS: We report a risk-adjusted, propensity score-matched, retrospective case-control study of clinical outcomes for inpatients who did not accept ABT (bloodless, n = 294) and those who did accept ABT (control, n = 1157). Multidisciplinary specialized care was rendered to the bloodless patients to conserve blood and optimize clinical outcomes. Differences in hemoglobin (Hb), mortality, five morbid outcomes, and hospital charges and costs were compared. Subgroups of medical and surgical patients were analyzed, and independent predictors of outcome were determined by multivariate analysis. RESULTS: Overall, mortality was lower in the bloodless group (0.7%) than in the control group (2.7%; p = 0.046), primarily attributed to the surgical subgroup. After risk adjustment, bloodless care was not an independent predictor of the composite adverse outcome (death or any morbid event; p = 0.91; odds ratio, 1.02; 95% confidence interval, 0.68-1.53). Discharge Hb concentrations were similar in the bloodless (10.8 ± 2.7 g/dL) and control (10.9 ± 2.3 g/dL) groups (p = 0.42). Total and direct hospital costs were 12% (p = 0.02) and 18% (p = 0.02) less, respectively, in the bloodless patients, a difference attributed to the surgical subgroup. CONCLUSIONS: Using appropriate blood conservation measures for patients who do not accept ABT results in similar or better outcomes and is associated with equivalent or lower costs. This specialized care may be beneficial even for those patients who accept ABT.