April 21, 2026
Prepared by Dr Edwin Uriel Suárez

Key points:

●      The authors outline 4 phases of the clinical ethics consultation process as endorsed by the American Society for Bioethics and Humanities. See Figure 1 in original paper.

1.     Consult Triage – identifying the ethical question and determining whether ethics involvement is appropriate.

2.     Intake Process – collecting relevant clinical, psychosocial, and regulatory information.

3.     Stakeholder Meetings and Additional Data Collection – clarifying facts, values, and areas of disagreement among patients, families, and clinicians.

4.     Ethical Analysis and Recommendations – synthesizing information and applying ethical frameworks such as principlism, virtue ethics, narrative ethics, feminist ethics, deontology, and consequentialism to generate transparent, ethically justified options.

●      Through 3 illustrative cases of ethical dilemmas arising from hematology cases, the manuscript highlights common ethical challenges (See Table 2 in original paper):

-        Patient requests for nonstandard interventions (clonal hematopoiesis).

-        Family–patient conflicts regarding pain management (sickle cell disease).

-        Parental refusal of diagnosis or treatment (pediatric leukemia).

Requesting support of the ethics team does not imply that the requestor (or any other individual involved in the care of the patient) is “unethical” or lacking in knowledge about ethical practice. See Table 1 in original paper for practical guidance for hematologists when considering requesting an ethics consultation. The authors emphasize that the purpose of ethics consultation is not to dictate clinical decisions but to facilitate ethical deliberation, promote understanding among stakeholders, and reduce clinicians’ moral distress. Ethics consult services are a vital resource to enhance patient care, support clinicians, and ensure that difficult choices are navigated with clarity, compassion, and integrity.

Key points:

●      Myelodysplastic neoplasms (or myelodysplastic syndromes, MDS) are characterized by dysplasia of one or more myeloid lineages, ineffective haematopoiesis, cytopenias, and a variable risk of progression to acute myeloid leukaemia. Incidence increases with age, with a median age at diagnosis of ~76 years in economically developed countries. MDS incidence is approximately 1.8-fold higher in men than in women.

●      Disease progression is driven by the stepwise acquisition of somatic mutations in hematopoietic stem cells. Clonal hematopoiesis of indeterminate (clinical) potential (CHIP) and clonal cytopenia of unknown significance (CCUS) play central roles, where mutations in TET2, DNMT3A, and ASXL1 (in ~80% of these patients) provide a competitive advantage within an inflammatory bone marrow microenvironment.

●      Occupational and environmental risks: Benzene exposure has the  strongest and best-characterized association with MDS. Therapy-related MDS accounts for ~10% of all cases and is linked to previous cytotoxic or radiologic therapy.

●      The transition from International Prognostic Scoring System revised (IPSS-R) to the  IPSS molecular (IPSS-M) has refined prognostication by integrating genomic data, resulting in the reclassification of 46% of patients—mostly to higher risk categories.

●      The treatment of patients with lower-risk MDS focuses on the improvement of cytopenias and associated symptoms, with an increasing number of agents, including erythropoiesis-stimulating agents, luspatercept, imetelstat and lenalidomide, administered based on specific disease characteristics (See Figure 3 in original paper)

●      Aside from transplantation, monotherapy with hypomethylating agents (HMAs), including azacitidine, decitabine, and oral decitabine plus cedazuridine, remains the mainstay of care for patients with higher-risk MDS owing to the failure of various randomized phase III trials testing HMAs with or without novel agents. The outcomes of patients with higher-risk MDS after HMA failure are dismal, with estimated survival durations of 6–8 months.

●      Allogeneic haematopoietic stem cell transplantation remains the only potentially curative therapeutic modality for patients with MDS, although the majority of patients are not candidates for such therapies owing to age, comorbidities and/or patient preferences.

●      While the addition of venetoclax showed promise in early trials, recent phase III data (VERONA trial) showed no significant overall survival benefit. Targeted inhibitors, such as ivosidenib for IDH1-mutant disease, are now FDA approved for relapsed/refractory settings (See Figure 4 in original paper).

Key points:

●       Pathobiological distinction. Classical hairy cell leukemia (HCL) is characterized by the BRAF-V600E mutation in >95% of cases. HCL-variant (HCLv) is BRAF wild-type and frequently associated with MAP2K1 mutations (coding for MEK1, the kinase phosphorylated by BRAF), and could have an inferior outcome.

○      The vast majority of HCL express somatically hypermutated immunoglobulin heavy chain variable (IGHV), but a minor subset with somatically unmutated IGHV (10% of cases) has been identified in one study to associate with inferior outcome after cladribine monotherapy.

●       Diagnostic markers. HCL clones typically express CD19, CD20, CD11c, CD25, CD103, CD123, and Annexin-1. HCLv generally lacks CD25, CD123, CD200, and Annexin-1, often presenting with prominent nucleoli and higher leukocyte counts.

●       Indications for therapy. Treatment is indicated for symptomatic patients or those with significant and worsening cytopenias (hemoglobin <10 g/dL, absolute neutrophil count <1.0 x 10⁹/L, or platelets <100 x 10⁹/L).

●       First-line HCL management. Purine analog (PA) monotherapy (cladribine or pentostatin) achieves high response rates. However, the addition of rituximab (concurrent or sequential) increases undetectable measurable residual disease rates and prolongs progression-free survival. See Figure 1 in original paper.

●       HCLv treatment. HCLv is poorly responsive to PA monotherapy. The standard of care is chemoimmunotherapy using cladribine plus rituximab.

●       Relapsed/fefractory HCL. Management is based on the duration of the first response. Early relapse (≤2 years) or refractory disease should be treated with vemurafenib + rituximab or an alternate PA + rituximab. Late relapse (>5 years) may allow for PA + rituximab re-challenge. See Figure 2 in original paper.

●       Special populations: In patients with active infection or frailty, BRAF inhibitors (± rituximab) or low-dose pentostatin are preferred to minimize treatment-related myelosuppression and immunosuppression.

●       Novel targeted agents: Bruton tyrosine kinase inhibitors (ibrutinib, zanubrutinib) and B-cell lymphoma 2 inhibitors (venetoclax) demonstrate activity in multi-refractory cases and represent important salvage options. 

Highlights:

●      The etiology of monoclonal gammopathy of undetermined significance (MGUS) and its progression to active disease remains poorly understood; however, several risk factors have been identified.

●      Dietary patterns or specific dietary components are unlikely to be strongly associated with the overall risk of MGUS development, suggesting they are unlikely primary drivers in early myelomagenesis.

A total of 75,422 individuals in the iStopMM trial (about 50% of thre total Icelandic population) had been screened for MGUS . Participants were given a food-frequency questionnaire and 27,217 (36%) responded. Of those, 1,020 (3.75%) had MGUS at the time of screening. Exposure was defined as the dietary intake of specific foods and adherence to five dietary patterns identified through principal component analysis ( "fruit & vegetable," "red meat," "sweet tooth," "bread," and "fish meal" ). Overall, no dietary patterns or specific dietary components were associated with the risk of MGUS. Although the authors observed a robust and dose-dependent relationship between higher dairy consumption and an increased risk of IgA MGUS.