Pub Date : 2025-01-01DOI: 10.1016/j.lrr.2025.100529
Fatemeh Ensafi Talemi , Soudeh Ghafouri-Fard
Imatinib is approved as the first-line treatment for newly diagnosed chronic myelogenous leukemia (CML). In spite of profound response in the majority of patients, resistance occurs in a subgroup of CML cases. Recently, it has been demonstrated that different classes of non-coding RNAs can modulate response to this tyrosine kinase inhibitor. Recognition of the role of these transcripts in this process not only expands our knowledge about the molecular mechanisms of imatinib resistance, but also provides novel strategies for combating this phenotype. The current review summarizes the role of non-coding RNAs in this process and suggests novel candidates for further studies in this field to enhance therapeutic response to imatinib.
{"title":"Impact of non-coding RNAs on resistance to imatinib in chronic myelogenous leukemia","authors":"Fatemeh Ensafi Talemi , Soudeh Ghafouri-Fard","doi":"10.1016/j.lrr.2025.100529","DOIUrl":"10.1016/j.lrr.2025.100529","url":null,"abstract":"<div><div>Imatinib is approved as the first-line treatment for newly diagnosed chronic myelogenous leukemia (CML). In spite of profound response in the majority of patients, resistance occurs in a subgroup of CML cases. Recently, it has been demonstrated that different classes of non-coding RNAs can modulate response to this tyrosine kinase inhibitor. Recognition of the role of these transcripts in this process not only expands our knowledge about the molecular mechanisms of imatinib resistance, but also provides novel strategies for combating this phenotype. The current review summarizes the role of non-coding RNAs in this process and suggests novel candidates for further studies in this field to enhance therapeutic response to imatinib.</div></div>","PeriodicalId":38435,"journal":{"name":"Leukemia Research Reports","volume":"24 ","pages":"Article 100529"},"PeriodicalIF":0.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144605228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01DOI: 10.1016/j.lrr.2025.100505
Zhaoyang Hong , Fan Wang
Background
Atypical Chronic Myeloid Leukemia (aCML) is a rare and aggressive myelodysplastic syndrome/myeloproliferative neoplasm. This study aimed to provide a comprehensive understanding of the epidemiology, clinical characteristics, and survival outcomes of aCML patients.
Methods
The study utilized data from the Surveillance, Epidemiology, and End Results (SEER) database from 2001 to 2020. The age-adjusted incidence rate (AIR) of aCML was calculated, and survival outcomes were analyzed using the Kaplan-Meier method and accelerated failure time (AFT) regression analysis.
Results
The AIR of aCML was found to be 0.024 per 100,000 person-years, with the highest rate observed in 2020. The incidence of aCML increased with age and was higher in males. The study cohort predominantly consisted of elderly White individuals, with an average age at diagnosis of 68.2 ± 15.3 years. The median overall survival (OS) and disease-specific survival (DSS) were 1.4 years and 1.7 years, respectively. Older age was independently associated with worse survival outcomes. Notably, treatment delay and chemotherapy did not significantly impact OS or DSS.
Conclusions
This study provides comprehensive insights into the epidemiology, clinical characteristics, and survival outcomes of aCML, highlighting its rarity, aggressive nature, and poor prognosis. Further research is needed to validate these findings and explore novel therapeutic strategies for improving outcomes in this challenging hematologic malignancy.
{"title":"Comprehensive analysis of Atypical chronic myeloid leukemia (aCML): Epidemiology, clinical features, and survival outcomes based on SEER database insights","authors":"Zhaoyang Hong , Fan Wang","doi":"10.1016/j.lrr.2025.100505","DOIUrl":"10.1016/j.lrr.2025.100505","url":null,"abstract":"<div><h3>Background</h3><div>Atypical Chronic Myeloid Leukemia (aCML) is a rare and aggressive myelodysplastic syndrome/myeloproliferative neoplasm. This study aimed to provide a comprehensive understanding of the epidemiology, clinical characteristics, and survival outcomes of aCML patients.</div></div><div><h3>Methods</h3><div>The study utilized data from the Surveillance, Epidemiology, and End Results (SEER) database from 2001 to 2020. The age-adjusted incidence rate (AIR) of aCML was calculated, and survival outcomes were analyzed using the Kaplan-Meier method and accelerated failure time (AFT) regression analysis.</div></div><div><h3>Results</h3><div>The AIR of aCML was found to be 0.024 per 100,000 person-years, with the highest rate observed in 2020. The incidence of aCML increased with age and was higher in males. The study cohort predominantly consisted of elderly White individuals, with an average age at diagnosis of 68.2 ± 15.3 years. The median overall survival (OS) and disease-specific survival (DSS) were 1.4 years and 1.7 years, respectively. Older age was independently associated with worse survival outcomes. Notably, treatment delay and chemotherapy did not significantly impact OS or DSS.</div></div><div><h3>Conclusions</h3><div>This study provides comprehensive insights into the epidemiology, clinical characteristics, and survival outcomes of aCML, highlighting its rarity, aggressive nature, and poor prognosis. Further research is needed to validate these findings and explore novel therapeutic strategies for improving outcomes in this challenging hematologic malignancy.</div></div>","PeriodicalId":38435,"journal":{"name":"Leukemia Research Reports","volume":"23 ","pages":"Article 100505"},"PeriodicalIF":0.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143437342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01DOI: 10.1016/j.lrr.2025.100542
Kun Chi , Lili Song
A 30-year-old woman with MDS with low blasts (MDS-LB) presented a somatic 67-kb copy number loss at 8q24.13 involving TRIB1, detected by single nucleotide polymorphism (SNP) array. Bone marrow analysis showed no mutations in common MDS genes (TP53, ASXL1, TET2, RUNX1) or karyotypic abnormalities (46, XX). Using oral epithelial DNA as a patient-matched control, SNP-array identified four hereditary uniparental disomies (UPDs) and a somatic TRIB1-containing deletion at 8q24.13. This deletion likely caused TRIB1 haploinsufficiency, reducing control over dysplastic clones and driving progression to MDS with increased blasts 2 (MDS-IB2) over three years. This first report of TRIB1 copy number loss in myeloid disorders highlights the value of SNP-array with patient-matched controls in distinguishing somatic variants, expanding MDS’s genetic profile and underscoring TRIB1’s context-dependent roles in oncogenesis.
{"title":"First reported TRIB1 copy number loss in myelodysplastic syndrome (MDS) revealed by single nucleotide polymorphism array (SNP-array) with patient-matched control","authors":"Kun Chi , Lili Song","doi":"10.1016/j.lrr.2025.100542","DOIUrl":"10.1016/j.lrr.2025.100542","url":null,"abstract":"<div><div>A 30-year-old woman with MDS with low blasts (MDS-LB) presented a somatic 67-kb copy number loss at 8q24.13 involving <em>TRIB1</em>, detected by single nucleotide polymorphism (SNP) array. Bone marrow analysis showed no mutations in common MDS genes (<em>TP53, ASXL1, TET2, RUNX1</em>) or karyotypic abnormalities (46, XX). Using oral epithelial DNA as a patient-matched control, SNP-array identified four hereditary uniparental disomies (UPDs) and a somatic <em>TRIB1</em>-containing deletion at 8q24.13. This deletion likely caused <em>TRIB1</em> haploinsufficiency, reducing control over dysplastic clones and driving progression to MDS with increased blasts 2 (MDS-IB2) over three years. This first report of <em>TRIB1</em> copy number loss in myeloid disorders highlights the value of SNP-array with patient-matched controls in distinguishing somatic variants, expanding MDS’s genetic profile and underscoring <em>TRIB1</em>’s context-dependent roles in oncogenesis.</div></div>","PeriodicalId":38435,"journal":{"name":"Leukemia Research Reports","volume":"24 ","pages":"Article 100542"},"PeriodicalIF":0.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144932327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01DOI: 10.1016/j.lrr.2025.100548
Chokri Ben Lamine , Mohammed Alshehri , Lara Samhan , Maha Abdullah Hassan , Tusneem Ahmed M. Elhassan , Riad Elfakih , Feras Abdulaziz Alfraih , Syed Osman Ahmed , Amr Hanbali
Background
Relapsed acute lymphoblastic leukemia (ALL) in adolescents and young adults (AYA) remains a high-risk scenario with limited evidence guiding optimal salvage regimens. Pediatric-inspired protocols have improved frontline outcomes in AYA-ALL, yet their applicability in relapse remains undefined.
Objective
To compare the clinical efficacy and toxicity of the pediatric-based UKALL R3 protocol versus the adult salvage fludarabine/cytarabine (FA) regimen in relapsed Philadelphia-negative AYA-ALL.
Methods
A retrospective cohort study was conducted at a single tertiary care center including 77 patients aged 14–40 years with relapsed AYA-ALL. Seventeen patients received the R3 regimen and sixty received the FA protocol. Primary endpoints included complete remission (CR) rate and overall survival (OS). Secondary endpoints assessed minimal residual disease (MRD) response, transplantation rates, and treatment-related toxicities.
Results
Baseline characteristics were comparable, though the FA cohort had older patients and higher-risk cytogenetics. CR rates were 60 % in R3 versus 76.3 % in FA (p=0.1). Median follow-up of 4 years showed numerically superior OS with R3 (53 % vs. 30.8 %, p=0.8). Toxicities varied: febrile neutropenia and hepatotoxicity were more frequent with FA, while mucositis and peripheral neuropathy predominated in R3. Infection-related deaths occurred less often in R3 (12.5 % vs. 25 %).
Conclusion
The pediatric-inspired R3 and adult-based FA regimens yielded similar survival and remission rates in relapsed AYA-ALL. Distinct toxicity profiles suggest that treatment selection should be individualized. Larger, prospective studies are warranted to validate the role of pediatric salvage protocols in this challenging population.
背景：青少年和青壮年（AYA）复发性急性淋巴细胞白血病（ALL）仍然是一个高风险的情况，指导最佳抢救方案的证据有限。儿科方案改善了AYA-ALL的一线预后，但其在复发中的适用性仍不明确。目的比较以儿科为基础的UKALL R3方案与成人补救性氟达拉滨/阿糖胞苷（FA）方案治疗复发性philadelphia -阴性AYA-ALL的临床疗效和毒性。方法在某三级医疗中心对77例14-40岁复发AYA-ALL患者进行回顾性队列研究。17名患者接受R3方案，60名患者接受FA方案。主要终点包括完全缓解（CR）率和总生存（OS）。次要终点评估最小残留病（MRD）反应、移植率和治疗相关毒性。结果：尽管FA队列患者年龄较大，细胞遗传学风险较高，但基线特征具有可比性。R3组的CR率为60%，FA组为76.3% （p=0.1）。中位随访4年显示R3的OS在数值上优于R3 （53% vs. 30.8%, p=0.8）。毒性各不相同：热性中性粒细胞减少症和肝毒性在FA中更为常见，而粘膜炎和周围神经病变在R3中占主导地位。R3组感染相关死亡较少（12.5% vs. 25%）。结论儿科启发的R3和成人为基础的FA方案在复发的AYA-ALL中具有相似的生存率和缓解率。不同的毒性特征表明治疗选择应个体化。需要更大规模的前瞻性研究来验证儿科抢救方案在这一具有挑战性的人群中的作用。
{"title":"Pediatric-inspired (R3) vs. Adult salvage (FA) chemotherapy in relapsed adolescents and young adults (AYA) acute lymphoblastic leukemia (ALL): A comparative outcome analysis","authors":"Chokri Ben Lamine , Mohammed Alshehri , Lara Samhan , Maha Abdullah Hassan , Tusneem Ahmed M. Elhassan , Riad Elfakih , Feras Abdulaziz Alfraih , Syed Osman Ahmed , Amr Hanbali","doi":"10.1016/j.lrr.2025.100548","DOIUrl":"10.1016/j.lrr.2025.100548","url":null,"abstract":"<div><h3>Background</h3><div>Relapsed acute lymphoblastic leukemia (ALL) in adolescents and young adults (AYA) remains a high-risk scenario with limited evidence guiding optimal salvage regimens. Pediatric-inspired protocols have improved frontline outcomes in AYA-ALL, yet their applicability in relapse remains undefined.</div></div><div><h3>Objective</h3><div>To compare the clinical efficacy and toxicity of the pediatric-based UKALL R3 protocol versus the adult salvage fludarabine/cytarabine (FA) regimen in relapsed Philadelphia-negative AYA-ALL.</div></div><div><h3>Methods</h3><div>A retrospective cohort study was conducted at a single tertiary care center including 77 patients aged 14–40 years with relapsed AYA-ALL. Seventeen patients received the R3 regimen and sixty received the FA protocol. Primary endpoints included complete remission (CR) rate and overall survival (OS). Secondary endpoints assessed minimal residual disease (MRD) response, transplantation rates, and treatment-related toxicities.</div></div><div><h3>Results</h3><div>Baseline characteristics were comparable, though the FA cohort had older patients and higher-risk cytogenetics. CR rates were 60 % in R3 versus 76.3 % in FA (p=0.1). Median follow-up of 4 years showed numerically superior OS with R3 (53 % vs. 30.8 %, p=0.8). Toxicities varied: febrile neutropenia and hepatotoxicity were more frequent with FA, while mucositis and peripheral neuropathy predominated in R3. Infection-related deaths occurred less often in R3 (12.5 % vs. 25 %).</div></div><div><h3>Conclusion</h3><div>The pediatric-inspired R3 and adult-based FA regimens yielded similar survival and remission rates in relapsed AYA-ALL. Distinct toxicity profiles suggest that treatment selection should be individualized. Larger, prospective studies are warranted to validate the role of pediatric salvage protocols in this challenging population.</div></div>","PeriodicalId":38435,"journal":{"name":"Leukemia Research Reports","volume":"24 ","pages":"Article 100548"},"PeriodicalIF":0.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145320237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01DOI: 10.1016/j.lrr.2024.100493
XS Bao, DH Gong, KG Zhou, W Huang
Abdominal multiple extramedullary plasmacytoma (EMP) is a rare disease. CD38-negative relapsed/refractory EMP after treatment with daratumumab has never been reported. In 2020, a patient with jaundice was diagnosed with plasmacytoma in another hospital, which progressed one year after receiving multiline therapy. In July 2021, he was admitted to our hospital and showed CD38-pogative plasmacytoma. The patient received 2 cycles of treatment including daratumumab, venetoclax and DCEP chemotherapy and achieved partial remission. However, he developed ascites and eventually died. Our case indicated that multiple EMP has much lower incidence and far worse prognosis than solitary EMP.
{"title":"A rare case of CD38-negative abdominal multiple extramedullary plasmacytoma and literature review","authors":"XS Bao, DH Gong, KG Zhou, W Huang","doi":"10.1016/j.lrr.2024.100493","DOIUrl":"10.1016/j.lrr.2024.100493","url":null,"abstract":"<div><div>Abdominal multiple extramedullary plasmacytoma (EMP) is a rare disease. CD38-negative relapsed/refractory EMP after treatment with daratumumab has never been reported. In 2020, a patient with jaundice was diagnosed with plasmacytoma in another hospital, which progressed one year after receiving multiline therapy. In July 2021, he was admitted to our hospital and showed CD38-pogative plasmacytoma. The patient received 2 cycles of treatment including daratumumab, venetoclax and DCEP chemotherapy and achieved partial remission. However, he developed ascites and eventually died. Our case indicated that multiple EMP has much lower incidence and far worse prognosis than solitary EMP.</div></div>","PeriodicalId":38435,"journal":{"name":"Leukemia Research Reports","volume":"23 ","pages":"Article 100493"},"PeriodicalIF":0.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11731487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142984853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01DOI: 10.1016/j.lrr.2025.100508
Hiroshi Kazama , Yan-Hua Wang , Junji Tanaka
Chronic myeloid leukemia (CML) is characterized by the presence of the BCR::ABL1 fusion protein with active tyrosine kinase activity. The BCR::ABL1 fusion protein induces the production of reactive oxygen species (ROS). DNA damage caused by ROS is involved in the mechanism of CML progression. Antioxidant systems include peroxiredoxins (PRDXs), which play various roles in hematological malignancies. Although tyrosine kinase inhibitors (TKIs) are known to affect ROS production, their effects on the expression of the antioxidants PRDX1 and PRDX2 remain unclear; thus, we aimed to evaluate the effects of TKIs on the expression of these PRDXs and ROS levels in CML cells. We found that TKIs, such as imatinib, nilotinib, and dasatinib, increased the gene expression of PRDX2 in K562 cells; however, only dasatinib increased the cytoplasmic protein expression of PRDX2. Additionally, while TKIs reduced the gene expression of PRDX1 in contrast to that of PRDX2, dasatinib increased the cytoplasmic protein expression of PRDX1. This discrepancy was linked to post-translational regulation through SUMOylation in cooperation with dasatinib. Our results suggest that the antioxidants PRDX1 and PRDX2 could serve as potential targets for TKIs in the treatment of CML.
{"title":"Tyrosine kinase inhibitors modulate the expression of peroxiredoxins 1 and 2 in chronic myeloid leukemia cells","authors":"Hiroshi Kazama , Yan-Hua Wang , Junji Tanaka","doi":"10.1016/j.lrr.2025.100508","DOIUrl":"10.1016/j.lrr.2025.100508","url":null,"abstract":"<div><div>Chronic myeloid leukemia (CML) is characterized by the presence of the BCR::ABL1 fusion protein with active tyrosine kinase activity. The BCR::ABL1 fusion protein induces the production of reactive oxygen species (ROS). DNA damage caused by ROS is involved in the mechanism of CML progression. Antioxidant systems include peroxiredoxins (PRDXs), which play various roles in hematological malignancies. Although tyrosine kinase inhibitors (TKIs) are known to affect ROS production, their effects on the expression of the antioxidants PRDX1 and PRDX2 remain unclear; thus, we aimed to evaluate the effects of TKIs on the expression of these PRDXs and ROS levels in CML cells. We found that TKIs, such as imatinib, nilotinib, and dasatinib, increased the gene expression of <em>PRDX2</em> in K562 cells; however, only dasatinib increased the cytoplasmic protein expression of PRDX2. Additionally, while TKIs reduced the gene expression of <em>PRDX1</em> in contrast to that of <em>PRDX2</em>, dasatinib increased the cytoplasmic protein expression of PRDX1. This discrepancy was linked to post-translational regulation through SUMOylation in cooperation with dasatinib. Our results suggest that the antioxidants PRDX1 and PRDX2 could serve as potential targets for TKIs in the treatment of CML.</div></div>","PeriodicalId":38435,"journal":{"name":"Leukemia Research Reports","volume":"23 ","pages":"Article 100508"},"PeriodicalIF":0.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143685842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01DOI: 10.1016/j.lrr.2025.100517
Muhammad Hassan Raza , Eiraj Khan , Alexis M Desjarlais , Salman Fazal
Introduction and Importance
Treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia (pH-positive ALL) in Jehovah’s Witness (JW) using chemotherapy agents, opens an ethically and morally challenging paradigm instead of their religious practices.
Case Presentation
We present a case of pH-positive B cell ALL in a Jehovah's Witness patient who refused the transfusion of blood as a part of their treatment regimen. We intended to treat this patient using a new “chemotherapy-free” approach and achieved Minimal Residual Disease (MRD) negative state with durable outcomes for the next three years.
Clinical Discussion
With “chemotherapy-free” regimen, we achieved complete molecular remission without any significant side effects in our patient.
Conclusion
Chemo-free approach is a promising opportunity to treat Jehovah’s witnesses with pH-positive B cell ALL as the haemoglobin and platelets remained above transfusion thresholds. However, further research is required to fully understand and implement this approach. Future clinical trials should consider including this unique patient population to better understand their needs and improve outcomes.
{"title":"Management of Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia in a Jehovah’s Witness using chemotherapy free regimen: A case report and review of literature","authors":"Muhammad Hassan Raza , Eiraj Khan , Alexis M Desjarlais , Salman Fazal","doi":"10.1016/j.lrr.2025.100517","DOIUrl":"10.1016/j.lrr.2025.100517","url":null,"abstract":"<div><h3>Introduction and Importance</h3><div>Treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia (pH-positive ALL) in Jehovah’s Witness (JW) using chemotherapy agents, opens an ethically and morally challenging paradigm instead of their religious practices.</div></div><div><h3>Case Presentation</h3><div>We present a case of pH-positive B cell ALL in a Jehovah's Witness patient who refused the transfusion of blood as a part of their treatment regimen. We intended to treat this patient using a new “chemotherapy-free” approach and achieved Minimal Residual Disease (MRD) negative state with durable outcomes for the next three years.</div></div><div><h3>Clinical Discussion</h3><div>With “chemotherapy-free” regimen, we achieved complete molecular remission without any significant side effects in our patient.</div></div><div><h3>Conclusion</h3><div>Chemo-free approach is a promising opportunity to treat Jehovah’s witnesses with pH-positive B cell ALL as the haemoglobin and platelets remained above transfusion thresholds. However, further research is required to fully understand and implement this approach. Future clinical trials should consider including this unique patient population to better understand their needs and improve outcomes.</div></div>","PeriodicalId":38435,"journal":{"name":"Leukemia Research Reports","volume":"24 ","pages":"Article 100517"},"PeriodicalIF":0.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144306787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01DOI: 10.1016/j.lrr.2025.100520
Bhaumik Shah , Mitra Abdollahi-Neisani , Pegah Taheri , Asya Varshavsky , Reza Nejati , Nicholas Mackrides
The WHO and ICC classifications lack standardized terminology to define the disease phase of chronic myeloproliferative neoplasms in extramedullary sites, particularly lymph nodes, when infiltrates resemble extramedullary hematopoiesis (EH). We report a lymph node case of extramedullary chronic myelomonocytic leukemia (CMML) in blast phase mimicking EH. Comprehensive genomic profiling, using chromosomal microarray and NGS-based sequencing, identified copy neutral loss of heterozygosity (cn-LOH), previously unreported in extramedullary CMML. We discuss challenges in determining the CMML disease phase in lymph nodes and review the literature to underscore the need for consensus terminology for cases not meeting myeloid sarcoma criteria.
{"title":"Diagnostic and taxonomic challenges in chronic myelomonocytic leukemia with lymph node involvement: A case report and mini-review","authors":"Bhaumik Shah , Mitra Abdollahi-Neisani , Pegah Taheri , Asya Varshavsky , Reza Nejati , Nicholas Mackrides","doi":"10.1016/j.lrr.2025.100520","DOIUrl":"10.1016/j.lrr.2025.100520","url":null,"abstract":"<div><div>The WHO and ICC classifications lack standardized terminology to define the disease phase of chronic myeloproliferative neoplasms in extramedullary sites, particularly lymph nodes, when infiltrates resemble extramedullary hematopoiesis (EH). We report a lymph node case of extramedullary chronic myelomonocytic leukemia (CMML) in blast phase mimicking EH. Comprehensive genomic profiling, using chromosomal microarray and NGS-based sequencing, identified copy neutral loss of heterozygosity (cn-LOH), previously unreported in extramedullary CMML. We discuss challenges in determining the CMML disease phase in lymph nodes and review the literature to underscore the need for consensus terminology for cases not meeting myeloid sarcoma criteria.</div></div>","PeriodicalId":38435,"journal":{"name":"Leukemia Research Reports","volume":"24 ","pages":"Article 100520"},"PeriodicalIF":0.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144306833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
We aimed to analyse the incidence of BCR::ABL1 kinase domain mutations in patients newly diagnosed with or undergoing treatment for chronic myeloid leukemia (CML) in Côte d’Ivoire, as well as to evaluate the predictive factors associated with treatment outcomes.
Methods
We evaluated 42 patients with suboptimal molecular response who underwent BCR::ABL1 kinase domain mutation screening. Sequencing was performed in collaboration with the Fred Hutchinson Cancer Research Center, Seattle, USA.
Results
Among the 42 patients, 16 (38.1%) were found to have known BCR::ABL1 point mutations. A total of nine distinct mutations were identified, with T315I being the most common (5). Three patients harbored compound mutations: one had T315I + M244V, another had G250E + E459K, and the third had H396P + E459K. The 5-year overall survival (OS) rate was significantly lower in patients with BCR::ABL1 mutations (85%; 95 % CI: 51.0%–96.1%) compared to those without mutations (100%). However, there was no statistically significant difference in OS between patients with T315I mutations (83.3 %; 95 % CI: 27.4%–97.5%) and those without T315I (83.3%; 95% CI: 5.9%–98.8%). Being in the chronic phase of the disease and having a low-risk ELTS score were identified as protective factors against the development of mutations.
Conclusion
Our findings support the recommendation for BCR::ABL1 mutation screening in CML patients with an inadequate initial response or evidence of loss of response. Screening is also advised at progression to the accelerated or blast phase, and in patients with high-risk ELTS scores, and mutation profiles may serve as important prognostic indicators.
{"title":"BCR::ABL1 kinase domain mutations and their predictive value for treatment outcomes in patients with chronic myeloid leukemia treated with first-line imatinib in a low-income setting: Experience from Côte d’Ivoire","authors":"Kouassi Gustave Koffi , Sara Akou Bognini , Dohoma Alexis Silué , Ismael Kamara , Ines Kouakou , Ruth Dieket , Emeraude N’dhatz , Boidy Kouakou , Danho Clotaire Nanho , Yannick Kouassi , David Tea Okou","doi":"10.1016/j.lrr.2025.100544","DOIUrl":"10.1016/j.lrr.2025.100544","url":null,"abstract":"<div><h3>Background</h3><div>We aimed to analyse the incidence of BCR::ABL1 kinase domain mutations in patients newly diagnosed with or undergoing treatment for chronic myeloid leukemia (CML) in Côte d’Ivoire, as well as to evaluate the predictive factors associated with treatment outcomes.</div></div><div><h3>Methods</h3><div>We evaluated 42 patients with suboptimal molecular response who underwent BCR::ABL1 kinase domain mutation screening. Sequencing was performed in collaboration with the Fred Hutchinson Cancer Research Center, Seattle, USA.</div></div><div><h3>Results</h3><div>Among the 42 patients, 16 (38.1%) were found to have known BCR::ABL1 point mutations. A total of nine distinct mutations were identified, with T315I being the most common (5). Three patients harbored compound mutations: one had T315I + M244V, another had G250E + E459K, and the third had H396P + E459K. The 5-year overall survival (OS) rate was significantly lower in patients with BCR::ABL1 mutations (85%; 95 % CI: 51.0%–96.1%) compared to those without mutations (100%). However, there was no statistically significant difference in OS between patients with T315I mutations (83.3 %; 95 % CI: 27.4%–97.5%) and those without T315I (83.3%; 95% CI: 5.9%–98.8%). Being in the chronic phase of the disease and having a low-risk ELTS score were identified as protective factors against the development of mutations.</div></div><div><h3>Conclusion</h3><div>Our findings support the recommendation for BCR::ABL1 mutation screening in CML patients with an inadequate initial response or evidence of loss of response. Screening is also advised at progression to the accelerated or blast phase, and in patients with high-risk ELTS scores, and mutation profiles may serve as important prognostic indicators.</div></div>","PeriodicalId":38435,"journal":{"name":"Leukemia Research Reports","volume":"24 ","pages":"Article 100544"},"PeriodicalIF":0.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145048325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01DOI: 10.1016/j.lrr.2025.100543
Eman Almatar, Sondus Alsharidah, Omnia A. Hashem
Children with Down syndrome (DS) have a 10–20-fold increased risk of acute lymphoblastic leukemia (ALL) and heightened chemotherapy toxicity. Blinatumomab, a bispecific CD19 × CD3 T-cell engager, offers targeted immunotherapy with reduced myelotoxicity. We describe a 9-year-old girl with DS diagnosed with B-cell precursor ALL in early 2021 who relapsed during maintenance in September 2023. After reinduction, she received two 28-day blinatumomab cycles: the first resulted in <5 % blasts and undetectable minimal residual disease (MRD), and the second was well tolerated. She remains in remission pending allogeneic hematopoietic stem cell transplantation, highlighting blinatumomab’s efficacy and safety as a bridge to transplantation.
{"title":"Management of relapsed acute lymphoblastic leukemia in a patient with down syndrome: A case report","authors":"Eman Almatar, Sondus Alsharidah, Omnia A. Hashem","doi":"10.1016/j.lrr.2025.100543","DOIUrl":"10.1016/j.lrr.2025.100543","url":null,"abstract":"<div><div>Children with Down syndrome (DS) have a 10–20-fold increased risk of acute lymphoblastic leukemia (ALL) and heightened chemotherapy toxicity. Blinatumomab, a bispecific CD19 × CD3 T-cell engager, offers targeted immunotherapy with reduced myelotoxicity. We describe a 9-year-old girl with DS diagnosed with B-cell precursor ALL in early 2021 who relapsed during maintenance in September 2023. After reinduction, she received two 28-day blinatumomab cycles: the first resulted in <5 % blasts and undetectable minimal residual disease (MRD), and the second was well tolerated. She remains in remission pending allogeneic hematopoietic stem cell transplantation, highlighting blinatumomab’s efficacy and safety as a bridge to transplantation.</div></div>","PeriodicalId":38435,"journal":{"name":"Leukemia Research Reports","volume":"24 ","pages":"Article 100543"},"PeriodicalIF":0.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145094825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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