ABSTRACT Background The sequential emergence of chronic myeloid leukemia (CML) following Philadelphia‐positive acute lymphoblastic leukemia (ALL) is exceedingly rare, and its biological basis remains uncertain. Case We report a 15‐year‐old boy initially diagnosed at age 4 with Philadelphia‐positive pre‐B ALL expressing p190 BCR::ABL1. He achieved deep molecular remission following chemotherapy per the COG AALL0232‐based high‐risk B‐ALL protocol plus imatinib. Approximately 5 years after his last documented follow‐up, he re‐presented with splenomegaly, leukocytosis, anemia, and thrombocytosis. Bone marrow findings supported chronic‐phase CML, confirmed by detection of BCR::ABL1 p210 (b2a2 and b3a2) with no detectable p190. Responses to imatinib and dasatinib were suboptimal, and kinase‐domain analysis identified a rare ABL1 c.1159T>A (p.Leu387Met) variant. He subsequently underwent matched‐related allogeneic hematopoietic stem cell transplantation and remains BCR::ABL1‐negative on nilotinib. Conclusion This case expands the spectrum of sequential Philadelphia‐positive leukemias by documenting p190‐positive pre‐B ALL followed by p210‐positive chronic‐phase CML, accompanied by detection of the rare L387M variant and suboptimal responses to imatinib and dasatinib. The biological relationship between the two Philadelphia‐positive malignancies remains uncertain, with possible explanations including evolution from a shared Philadelphia‐positive precursor, therapy‐related leukemogenesis, or an independent second malignancy. This case provides unique insight into the biological complexity of sequential Philadelphia‐positive leukemias and adds to the evolving literature regarding the clinical significance of the L387M variant in TKI response. The unsupervised TKI interruption underscores that any consideration of treatment discontinuation should occur only under specialist supervision with close molecular monitoring, while the discordance between the observed response and reported L387M sensitivity patterns warrants further investigation.
ABSTRACT Background Atypical teratoid/rhabdoid tumors (ATRTs) are aggressive pediatric CNS malignancies with < 30% 5‐year survival despite multimodal therapy. No prior studies have explored ferroptosis induction in ATRT. Aims To determine whether GPR68 inhibition by ogremorphin (OGM) induces ATF4 ‐dependent ferroptosis in ATRT cell lines and whether SLC7A11 blockade (erastin, ERA) confers similar sensitivity. Methods CHLA‐02‐ATRT and CHLA‐06‐ATRT cell lines were treated with OGM or ERA. Viability (CellTiter‐Glo), GSH levels (GSH‐Glo), lipid peroxidation (BODIPY 581/591 C11), and gene expression (qRT‐PCR: ATF4 , HMOX1 , SLC7A11 , TFRC ) were assessed. Genetic validation used GPR68/ATF4 shRNA, overexpression, and an ATF4 luciferase reporter. Statistics: Student's t ‐test with Bonferroni correction (R 4.4.0). Results Both cell lines were sensitive to OGM‐ and ERA‐induced ferroptosis, with CHLA‐02‐ATRT significantly more responsive to OGM than ERA. OGM/ERA depleted GSH, increased lipid peroxidation, and upregulated ATF4 , HMOX1 , and SLC7A11 mRNA expression. OGM induced TFRC in both cell lines; high‐dose ERA upregulated TFRC in CHLA‐02‐ATRT only. GPR68 knockdown reduced viability, while overexpression or Ogerin increased proliferation. OGM activated ATF4 transcription, and ATF4 overexpression decreased cell survival. ATF4 knockdown rescued OGM‐treated cells. Conclusion GPR68 inhibition triggers ATF4 ‐dependent ferroptosis in ATRT. SLC7A11 blockade by ERA paralleled the effects of ferroptosis by OGM. These data establish a novel therapeutic strategy with strong translational potential.
ABSTRACT Introduction Breast cancer continues to be a leading cause of morbidity and mortality worldwide, with an especially severe impact in low‐resource settings. In such contexts, delayed diagnosis, limited diagnostic capacity, and inadequate access to treatment contribute to poor survival outcomes. However, little is known about how these factors influence survival patterns specifically in southern Ethiopia, highlighting the need for locally generated data to guide interventions. Methodology A hospital‐based retrospective cohort study was conducted among 507 breast cancer patients attending selected hospitals in southern Ethiopia. Data were collected by two trained BSc nurses using an Open Data Kit (ODK) tool. Descriptive statistics were presented using tables and graphs, while bivariable, and multivariable Cox regression models were used to identify independent predictors of survival. Results A total of 507 medical records were reviewed, of which 492 eligible women were included in the final analysis. The overall survival rates were 54.5% at 2 years and 23.9% at 3 years. In multivariable Cox regression analysis, advanced stage had a higher hazard of death (AHR = 1.73, 95% CI: 1.19–2.51). Poor NPI was also associated with increased mortality (AHR = 2.30, 95% CI: 1.50–5.10). Patients with an NLR < 3 had a lower hazard of death (AHR = 0.68, 95% CI: 0.47–0.97), as did those who received hormonal therapy (AHR = 0.64, 95% CI: 0.44–0.92). Conclusion Advanced‐stage disease and poorer NPI were associated with a higher hazard of death from any cause, while lower NLR and hormonal therapy were associated with better overall survival. Strengthening early diagnosis and ensuring appropriate treatment may improve overall survival among women with breast cancer in resource‐constrained settings.
ABSTRACT Background Immune checkpoint inhibitors (ICIs), including nivolumab, have significantly improved cancer care. However, due to high costs, there is a significant financial barrier to their widespread access. Emerging evidence shows biological plausibility as well as efficacy of low‐dose nivolumab across different cancers. Aims This exploratory study aims to investigate the clinical outcomes of low‐dose nivolumab in cancer treatment to explore the potential to improve its access by reducing costs, especially in resource‐limited settings. Methods and Results Data on patients with various malignancies treated with fixed 20 or 40 mg of nivolumab every 3 weeks were retrospectively analyzed. Response to the treatment, including the best objective response rate, best disease control rate, and adverse events, was reported. The Kaplan–Meier method was used to determine progression‐free survival and overall survival. The patient cohort of 31 patients with various tumors received a median of 9 cycles (range, 2–20) of low‐dose nivolumab therapy for 5.7 months (range, 0.7–17.1). Median follow‐up was 8.6 months (95% CI, 7.1–12.9). Disease control was achieved in 21/31 (67.7%) patients, with the best objective response rate of 51.6%. The median progression‐free survival was 8.8 months (95% CI, 6.6‐not reached) and overall survival was 14.8 months (95% CI, 11.1‐not reached). At the end of the study period, 3/31 patients had a radiologic complete response, 9/31 had a partial response, 4/31 had stable disease, and 6/31 had progressive disease, and 3/31 were not evaluable; 6 patients died during this period. The responses achieved were sustainable for a median of 4 months (range, 0.8–8.2). Only 5 patients developed adverse events of grade 2 or 3. Conclusions Low‐dose nivolumab shows preliminary efficacy in resource‐constrained settings. Further research should explore optimal dosing and scheduling for low‐dose immunotherapy and evaluate its efficacy and safety through larger, homogeneous studies.
ABSTRACT Background Adolescent and young adult childhood cancer survivors (AYA‐CCS) face elevated risks of chronic health conditions and premature mortality further exacerbated by poor lifestyle behaviors including physical inactivity, poor nutrition, and substance use. Behavioral interventions are essential for supporting long‐term health in this population; however, the evidence remains fragmented and unbalanced across lifestyle domains. This scoping review aimed to identify and describe behavioral interventions promoting healthy lifestyles among AYA‐CCS, focusing on four domains (physical activity, nutrition, alcohol use, and tobacco use), and to map the behavior change techniques employed. Following the Joanna Briggs Institute methodology, a comprehensive search was conducted. Eligible studies targeted AYA‐CCS aged 13–39 years and included interventions addressing at least one of the four behavioral domains. Records were published between 2005 and 2025. Data were extracted using the Template for Intervention Description and Replication (TIDieR) checklist and categorized according to the Behavior Change Wheel to identify intervention functions and sources of behavior change. Findings The search identified 6170 records, 23 articles met inclusion criteria (representing 17 distinct interventions). Most interventions (76.5%) targeted physical activity. Education, enablement, and training were the most frequently used intervention functions, primarily addressing psychological capability and reflective motivation. Strategies targeting automatic motivation, physical capability, or social opportunity were far less common. Only three multi‐domain interventions were identified. Conclusion Current behavior change interventions for AYA‐CCS are dominated by physical activity programs, with limited attention to nutrition, alcohol, and tobacco use. While many interventions were theory‐informed, important gaps remain in fidelity reporting, multi‐behavioral targeting, and explaining mechanisms of change.
