To examine inequities affecting the diagnosis, disease-specific treatment, and supportive care of hematologic malignancies in resource-constrained settings, and to critically evaluate resource-adapted strategies intended to address these barriers. Evidence identifies limited access to hematopathology, flow cytometry, cytogenetic and molecular testing, measurable residual disease assessment, and specialized imaging as major diagnostic barriers. Treatment inequities include delayed or of access to effective therapies, limited delivery of risk- or response adapted protocols and inadequate access to transplantation and cell therapy. Tiered diagnostic networks, resource-adapted protocols, quality-assured generics and biosimilars, shared-care models, and selective use of telemedicine may expand access. However, supporting evidence is largely observational and provides limited information on cost-effectiveness, scalability, and survival benefit. Reducing inequities in hematologic cancer care requires prioritizing interventions that directly improve diagnostic and treatment decisions and can be sustained within local resources. Resource-adapted diagnostic pathways, disease-specific treatment protocols, adequate supportive care, patient navigation, and selective digital follow-up provide pragmatic approaches. These interventions should be evaluated using clinically relevant outcomes, including diagnostic accuracy, treatment delay and abandonment, toxicity, cost, and survival.
The field of plasma cell dyscrasias has undergone dramatic evolution in recent yeast due to rapid therapeutic advances. While exciting, the growth of novel therapeutic strategies has created significant evidence gaps which cannot all be feasibly addressed with dedicated prospective trials. The role of real-world data (RWD) and real-world evidence (RWE) in informing management has thus also expanded. We aim to review the use of RWD and RWE in PCD management. RWD has been used significantly to assess short- and long-term toxicities associated with rapidly expanding treatment modalities such as cellular therapies that were not explored in RCTs. Other RWE has shown that clinical efficacy of newer treatment options is maintained in patient populations that would be excluded from RCT participation. RWE has also lent greater support for and generated new ideas for optimal therapeutic sequencing in PCD. Furthermore, RWE has allowed for the development of treatment ideas for less common PCD that have not been studied in RCTs. The use of RWD and RWE in the field of PCDs has effectively supplemented the use of RCTs in expanding the treatment options available to combat PCDs. As this field continues to expand at a rapid pace, RWD and RWE will continue to be needed as a source of data to support new treatments.
Outdoor air pollution (OAP) is a major global environmental health threat associated with respiratory disease and solid tumors, with growing evidence linking it to hematologic malignancies. This review summarizes the molecular mechanisms and epidemiologic evidence connecting OAP exposure to acute and chronic leukemias, lymphomas, myelodysplastic syndromes (MDS), clonal hematopoiesis of indeterminate potential (CHIP), and multiple myeloma (MM). Pollutants implicated in hematologic carcinogenesis include particulate matter (PM), benzene, nitrogen dioxide (NO₂), sulfur dioxide (SO₂), arsenic, and ethylene oxide. Molecular mechanisms include oxidative stress, DNA damage, epigenetic dysregulation, chronic inflammation, and hematopoietic stem cell dysfunction. Epidemiologic evidence is strongest for acute myeloid leukemia (AML), particularly with benzene exposure. Acute lymphoblastic leukemia (ALL) has also been associated with traffic-related pollution, NO₂, and PM exposure, though findings are less consistent. Certain lymphoma subtypes demonstrate pollutant-specific associations, while emerging evidence suggests possible links between OAP exposure and MDS and CHIP. In contrast, evidence for chronic leukemias and MM remains limited. Despite limitations, including exposure misclassification and residual confounding, cumulative molecular and epidemiologic evidence supports OAP as an important and potentially modifiable risk factor for hematologic malignancies. OAP exposure disproportionately affects racial and ethnic minorities, low-income communities, and rapidly industrializing regions, magnifying existing health disparities. Further research, environmental policy reform, and public health interventions are needed to reduce exposure and disease burden. HSC: hematopoietic stem cell. Created in BioRender. Murli, H. (2026) https://BioRender.com/tkhy5k7
Targeted immunotherapies have transformed the treatment of relapsed and refractory B-cell acute lymphoblastic leukemia (B-ALL), yet their efficacy depends on sustained expression of lineage-associated surface antigens. This review examines how antigen-directed pressure reshapes the biology of resistance, distinguishes canonical antigen escape from lineage plasticity, and clarifies the genomic contexts, diagnostic challenges, and therapeutic implications of these distinct escape routes. Under antigen-directed pressure, leukemia may escape through antigen downregulation, alternative splicing, acquired genetic alteration, or epitope disruption — mechanisms that generally preserve B-lineage identity and often remain addressable with alternative lineage-directed therapy. A biologically distinct route is lineage plasticity, in which cells destabilize lineage commitment or undergo overt lineage switch; clinical outcomes are poor, with a median overall survival of approximately 4.8 months in the largest reported series. Lineage switch is enriched within permissive genomic contexts, most notably KMT2A-rearranged leukemia, which accounted for the majority of B-ALL-to-acute myeloid leukemia or mixed-phenotype switches in a large international cohort. By contrast, CD19-negative antigen escape is more strongly associated with TP53 mutations and preserves B-lineage identity. Whether switching reflects selection of pre-existing subclones, active epigenetic reprogramming, or both remains unresolved. As antigen-directed therapies move into frontline use, distinguishing antigen escape from true lineage transformation is becoming essential for relapse surveillance, disease classification, therapeutic sequencing, and the design of strategies to prevent resistance.
Immunotherapeutic strategies for the treatment of lymphomas are rapidly expanding and can deliver durable remissions to patients with historically limited treatment options. Patient-reported outcomes (PROs) provide direct measurement of symptoms, functioning, and health-related quality of life (HRQoL), complementing physician-assessed toxicities and enabling a more comprehensive assessment of “treatment tolerability,” defined as the willingness of patients to adhere to treatment dose and schedule based on symptom burden and functioning. In this review, we demonstrate that when PROs are incorporated into clinical research, we gain a better understanding of treatment tolerability, particularly of novel immunotherapies, which confer distinct toxicity profiles compared with traditional chemoimmunotherapy. As survival improves, we argue that PROs should be incorporated as a primary or co-primary endpoint in most modern clinical trials, rather than as a point of interest in exploratory analyses. In patients with lymphoma, baseline and longitudinal HRQoL are prognostic of progression-free and overall survival. However, persistent discordance between clinician-graded adverse events (AEs) and patient-reported symptomatic AEs suggests that current trial endpoints focused primarily on safety and survival incompletely capture the patient experience, particularly in the context of novel immunotherapy-related toxicities. PROs are essential for interpreting modern lymphoma immunotherapies, where acute and chronic toxicities coexist with the promise of long-term remissions. Despite broad consensus of their utility, PRO analysis from seminal lymphoma immunotherapy trials remains inconsistent, and there remain significant gaps in the literature regarding the true patient-reported tolerability of emerging therapeutic regimens. Future trials should adopt harmonized PRO strategies (including symptom and functional domains), define meaningful thresholds for minimally important differences, and integrate real-world PRO data prospectively to better align clinical trial data with patient-centered treatment tolerability.
