Philadelphia-negative myeloproliferative neoplasms (MPNs) predominantly affect older adults, yet individuals over 65 years remain underrepresented in clinical trials, limiting evidence-based guidance for the most affected population. Aging can profoundly modify MPN biology through clonal hematopoiesis, chronic inflammation, vascular aging, and marrow senescence. This can amplify thrombotic risk, symptom burden, and treatment intolerance. These biological changes intersect with multimorbidity, frailty, and polypharmacy to create a distinct clinical phenotype that challenges traditional age-based treatment paradigms. This narrative review synthesizes current evidence on how aging influences therapeutic decision-making across ET, PV, and MF. In cytoreductive therapy, hydroxycarbamide remains the mainstay for older adults. Interferon-based therapies may offer disease-modifying benefits in appropriately selected older patients, although evidence regarding their comparative tolerability and safety in very elderly and frail populations remains limited. JAK inhibitors provide meaningful symptomatic and splenic benefit across age groups, though cytopenias, dose reductions, and treatment interruptions are more frequent in older patients due to diminished marrow reserve and competing comorbidities. Antithrombotic management requires careful balancing of heightened thrombotic risk against age-related bleeding hazards, particularly in the context of atrial fibrillation, renal impairment, and acquired von Willebrand syndrome. Polypharmacy further complicates care through drug–drug interactions and altered pharmacokinetics. Beyond disease modification, symptom burden—especially fatigue, pruritus, and functional decline—often dominates quality-of-life priorities for older adults. Integrating geriatric assessment, competing risks frameworks, and patient-centered outcomes is essential to delivering biologically informed, goal-aligned care. Overall, management of older adults with MPNs must transition to personalized strategies that reflect aging biology, functional reserve, and individual priorities.
Background: The presence of cancer cells in the bone marrow can cause blood cell abnormalities; when bone marrow metastasis is suspected, aspiration is performed to test for hematological disorders. However, the usefulness of combining cell surface markers with flow cytometry analysis (FCM) in this situation has not been verified. Methods: To review the clinical efficacy of FCM for detecting bone marrow involvement in cancer patients, we searched articles in PubMed using the keywords [bone marrow involvement] × [flow cytometry] among cancer types. To present an example case, we examined the bone marrow of cancer patients with cytopenia and analyzed the characteristics of the cell surface antigens. Bone marrow aspiration was performed from the iliac bone, and smear specimens were examined using May–Giemsa staining. We used a Beckman Coulter NAVIOS for FCM analysis and routine panels of myeloid and lymphoid neoplasms for surface marker analysis. Results: We reviewed the reported flow cytometric characteristics of bone marrow involvement in sarcomas, germ cell tumors, and carcinomas. Neuroblastoma and rhabdomyosarcoma commonly demonstrated CD45-negative/CD56-positive immunophenotypes, while epithelial markers such as EpCAM or cytokeratins were useful in selected carcinoma subtypes. FCM facilitated the identification of suspicious non-hematopoietic cell populations within bone marrow specimens, particularly when conventional morphological findings were subtle or equivocal. However, the diagnostic utility of individual markers varied among tumor types, and definitive lineage assignment required integration with morphology, histology, immunohistochemistry, and clinical findings. Conclusions: The diagnostic utility of FCM in detecting bone marrow involvement is still under investigation, and it is used to supplement microscopic diagnosis. CD56 or epithelial markers in the CD45-negative fraction are considered useful markers in some types of cancers (neuroblastoma, rhabdomyosarcoma, gastric cancer, and small-cell lung cancer) for detecting abnormal cells that have spread from other primary sites. In several cancer types (germ cell tumors, breast cancer, non-small-cell lung cancer, and urinary tract cancer), the standard FCM markers are not present. This narrative review is explicit in its educational point, which is based on practical cases.
Background/Objectives: Systemic inflammation-derived indices, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII), have been proposed as convenient and cost-effective predictive markers of mortality and complications in patients with pulmonary embolism (PE). We aimed to evaluate the prognostic performance of hematological inflammatory indices for in-hospital adverse outcomes among Mongolian patients diagnosed with PE. Methods: This multicenter retrospective study enrolled patients admitted to three tertiary-level hospitals in Ulaanbaatar, Mongolia, with a confirmed diagnosis of PE between September 2019 and January 2025. Data were collected retrospectively from electronic medical records. We calculated the NLR, PLR, and SII using standard formulas. All patients were stratified according to the sPESI. Moreover, we determined the prognostic performance of hematological indices for in-hospital adverse events. Results: We analyzed information on 232 patients with a confirmed diagnosis of PE. According to sPESI scoring, 69.8% (162) were in the high-risk group, with significant differences in comorbidity and age over 60 years (p < 0.001). The most common symptoms were dyspnea, chest pain, cough, leg pain, and hemoptysis. The median NLR was 2.48 (1.66–5.08) in the low-risk group and 4.21 (2.04–11.35) in the high-risk group (p = 0.001). The median SII level was significantly higher in the high-risk group than in the low-risk group (p = 0.037). However, there was no significant difference in PLR level between the two study groups. ROC analysis of hematological indices for predicting in-hospital adverse outcomes was limited, with poor and non-significant discriminatory performance. Conclusions: In cases of acute pulmonary embolism, elevated inflammatory indices, NLR and SII, were associated with higher sPESI risk stratification. However, their probability to predict in-hospital adverse events was limited by ROC analysis.
Background/Objectives: Myelofibrosis (MF) is a clonal myeloproliferative neoplasm driven by dysregulated JAK-STAT signaling, characterized by progressive marrow fibrosis, splenomegaly, constitutional symptoms, and increased risk of leukemic transformation. Allogeneic hematopoietic stem cell transplantation (allo-HCT) remains the only potentially curative intervention. In Italy, allo-HCTs for myeloproliferative neoplasms (MPN, i.e., myelofibrosis, polycythaemia vera, and essential thrombocythaemia combined) increased by 163% from 2015 to 2025; MF-specific procedure counts were not separately available in this registry export, so this figure should not be read as MF-specific, with MPN accounting for 8% of all allogeneic procedures (n = 171) in 2025, showing a 29.5% year-on-year increase from 2024. Concurrently, the demographic profile shifted, with individuals aged 60 and over representing 38% of all recipients, surpassing other age groups for the first time in 2025. Results: This review synthesizes current evidence on transplant indications and timing, pre-transplant management, donor selection, and conditioning regimen optimization, emphasizing the emerging role of treosulfan-based and dual-alkylator platforms, including the thiotepa–treosulfan–fludarabine (TTF) regimen. Post-transplant molecular MRD monitoring and relapse management are also discussed. Three-year overall survival in myelofibrosis ranges from about 59% to 67%, depending on donor type, with outcomes improving due to better patient selection, optimized conditioning, and supportive care. Conclusions: Prospective randomized trials are urgently needed to validate optimal conditioning intensity, the role of novel JAK inhibitors in the peri-transplant period, and MRD-guided pre-emptive strategies.
Metallothioneins (MTs) are cysteine-rich metal-binding proteins traditionally recognized for their roles in metal homeostasis and antioxidant defense. Recent studies have revealed broader and functionally diverse roles of MT isoforms in acute myeloid leukemia (AML). This review summarizes current evidence regarding MT-mediated regulation of leukemic cell survival, differentiation, and therapy-associated stress adaptation. MT1 family members, particularly MT1X and MT1G, have been associated with proliferation, chemoresistance, and differentiation blockade in specific experimental contexts, whereas MT2A and MT3 exhibit tumor-suppressive effects in selected AML models. MT isoforms also participate in oxidative stress adaptation and redox regulation, including responses to azacitidine, doxorubicin, and ferroptotic stress. However, the available evidence is derived largely from cell-line studies, selected molecular subtypes, transcriptomic analyses, and limited primary-patient datasets. Accordingly, isoform-specific MT functions should be interpreted as context-dependent rather than uniformly applicable across AML. Further validation in independent primary AML cohorts and genetically defined subtypes is required to establish their clinical utility as biomarkers or therapeutic targets.
