Pub Date : 2026-01-01DOI: 10.1016/j.lrr.2025.100556
Donia Bouhoula, Haifa Regaieg, Hela Abroug, Nesrine Ben Sayed, Yossra Ben Youssef
Pediatric acute myeloid leukemia outcomes in resource-limited regions remain understudied, particularly regarding how regional epidemiologic patterns interact with prognostic determinants. Our Tunisian cohort (n=68) reveals distinct pediatric AML features: older presentation (median 11 years), male predominance (63%), and unexpected AML2 subtype prevalence (35%). Cytogenetics showed 24% favorable-risk and 22% adverse-risk cases. Treatment outcomes correlated strongly with risk stratification, emphasizing the need for adapted diagnostic protocols in resource-conscious settings to optimize care pathways.
{"title":"Pediatric AML in Sousse, Tunisia: Epidemiologic patterns and hierarchical prognostic factors","authors":"Donia Bouhoula, Haifa Regaieg, Hela Abroug, Nesrine Ben Sayed, Yossra Ben Youssef","doi":"10.1016/j.lrr.2025.100556","DOIUrl":"10.1016/j.lrr.2025.100556","url":null,"abstract":"<div><div>Pediatric acute myeloid leukemia outcomes in resource-limited regions remain understudied, particularly regarding how regional epidemiologic patterns interact with prognostic determinants. Our Tunisian cohort (n=68) reveals distinct pediatric AML features: older presentation (median 11 years), male predominance (63%), and unexpected AML2 subtype prevalence (35%). Cytogenetics showed 24% favorable-risk and 22% adverse-risk cases. Treatment outcomes correlated strongly with risk stratification, emphasizing the need for adapted diagnostic protocols in resource-conscious settings to optimize care pathways.</div></div>","PeriodicalId":38435,"journal":{"name":"Leukemia Research Reports","volume":"25 ","pages":"Article 100556"},"PeriodicalIF":0.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145938759","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 : 2026-01-01DOI: 10.1016/j.lrr.2025.100558
Kaiqiong Liao , Chong Guo , Min Zhang , Xiaobin Lv , Jinhua Yan
Objective
The objective of this research is to explore the anti-leukemic properties of CDK4/6 inhibitors when used alongside BET inhibitors for treating acute myeloid leukemia (AML), as well as to clarify the molecular mechanisms involved.
Methods
Cell viability was assessed using the CCK-8 assay following treatment of AML cells with varying doses of SHR6390, a CDK4/6 inhibitor, and OTX015, a BET inhibitor.The time- and dose-dependent inhibitory effects of these two drugs on AML cells were assessed, and the respective IC50 and combination index (CI) values after co-treatment were calculated. The effects of SHR6390 and OTX015 on the growth potential of AML cells were additionally examined through soft agar colony formation assays and flow cytometry. Furthermore, RNA sequencing and Western blot analysis were conducted on cells treated with both drugs. The aim of this study is to explore the mechanism by which SHR6390 and OTX015 synergistically inhibit the proliferation of AML cells.The anti-tumor activity of SHR6390 and/or OTX015 in AML xenograft mice was also investigated through animal experiments.
Results
1. Either the CDK4/6 inhibitor SHR6390 or the BRD4 inhibitor OTX015, or a combination of the two, were employed to hinder both the survival and proliferation of cell lines associated with acute myeloid leukemia, showing a synergistic effect. 2. The combined application of SHR6390 and OTX015 markedly suppresses the invasive and migratory capacities of acute myeloid leukemia cells.3. The use of both SHR6390 and OTX015 induces apoptosis in acute myeloid leukemia cells while also disrupting cell cycle progression, leading to a halt before DNA replication occurs. 4. SHR6390 and OTX015 hinder the proliferation of acute myeloid leukemia cells by targeting both the PI3K-AKT-mTOR and the Wnt-β-Catenin pathway. 5. SHR6390 and OTX015 Synergistically Inhibit the Growth of AML Xenografts In Vivo.
{"title":"The synergistic tumor suppressor effect of CDK4/6 inhibitors and BRD4 inhibitors in acute myeloid leukemia","authors":"Kaiqiong Liao , Chong Guo , Min Zhang , Xiaobin Lv , Jinhua Yan","doi":"10.1016/j.lrr.2025.100558","DOIUrl":"10.1016/j.lrr.2025.100558","url":null,"abstract":"<div><h3>Objective</h3><div>The objective of this research is to explore the anti-leukemic properties of CDK4/6 inhibitors when used alongside BET inhibitors for treating acute myeloid leukemia (AML), as well as to clarify the molecular mechanisms involved.</div></div><div><h3>Methods</h3><div>Cell viability was assessed using the CCK-8 assay following treatment of AML cells with varying doses of SHR6390, a CDK4/6 inhibitor, and OTX015, a BET inhibitor.The time- and dose-dependent inhibitory effects of these two drugs on AML cells were assessed, and the respective IC50 and combination index (CI) values after co-treatment were calculated. The effects of SHR6390 and OTX015 on the growth potential of AML cells were additionally examined through soft agar colony formation assays and flow cytometry. Furthermore, RNA sequencing and Western blot analysis were conducted on cells treated with both drugs. The aim of this study is to explore the mechanism by which SHR6390 and OTX015 synergistically inhibit the proliferation of AML cells.The anti-tumor activity of SHR6390 and/or OTX015 in AML xenograft mice was also investigated through animal experiments.</div></div><div><h3>Results</h3><div>1. Either the CDK4/6 inhibitor SHR6390 or the BRD4 inhibitor OTX015, or a combination of the two, were employed to hinder both the survival and proliferation of cell lines associated with acute myeloid leukemia, showing a synergistic effect. 2. The combined application of SHR6390 and OTX015 markedly suppresses the invasive and migratory capacities of acute myeloid leukemia cells.3. The use of both SHR6390 and OTX015 induces apoptosis in acute myeloid leukemia cells while also disrupting cell cycle progression, leading to a halt before DNA replication occurs. 4. SHR6390 and OTX015 hinder the proliferation of acute myeloid leukemia cells by targeting both the PI3K-AKT-mTOR and the Wnt-β-Catenin pathway. 5. SHR6390 and OTX015 Synergistically Inhibit the Growth of AML Xenografts In Vivo.</div></div>","PeriodicalId":38435,"journal":{"name":"Leukemia Research Reports","volume":"25 ","pages":"Article 100558"},"PeriodicalIF":0.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145977084","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 : 2026-01-01DOI: 10.1016/j.lrr.2025.100557
Donia Bouhoula , Haifa Regaieg , Hela Abroug , Nesrine Ben Sayed , Yossra Ben Youssef
Treating pediatric acute myeloid leukemia in resource-limited settings presents unique therapeutic challenges. This study shares 19 years of experience from a Tunisian center, focusing on practical treatment outcomes. Our pediatric AML cohort (n=68) shows 50% initial remission rates (75% with idarubicin vs 31% novantrone) and 9% induction mortality. Despite salvage therapy (43% CR2), 5-year survival remained at 33%, constrained by high relapse (53%) and limited transplant access (21%). These results highlight critical needs: optimized frontline therapy and expanded salvage options for refractory cases.
{"title":"Long-term outcomes of pediatric AML in Tunisia: Lessons from 19 years of practice in Sousse","authors":"Donia Bouhoula , Haifa Regaieg , Hela Abroug , Nesrine Ben Sayed , Yossra Ben Youssef","doi":"10.1016/j.lrr.2025.100557","DOIUrl":"10.1016/j.lrr.2025.100557","url":null,"abstract":"<div><div>Treating pediatric acute myeloid leukemia in resource-limited settings presents unique therapeutic challenges. This study shares 19 years of experience from a Tunisian center, focusing on practical treatment outcomes. Our pediatric AML cohort (n=68) shows 50% initial remission rates (75% with idarubicin vs 31% novantrone) and 9% induction mortality. Despite salvage therapy (43% CR2), 5-year survival remained at 33%, constrained by high relapse (53%) and limited transplant access (21%). These results highlight critical needs: optimized frontline therapy and expanded salvage options for refractory cases.</div></div>","PeriodicalId":38435,"journal":{"name":"Leukemia Research Reports","volume":"25 ","pages":"Article 100557"},"PeriodicalIF":0.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145938760","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 : 2026-01-01DOI: 10.1016/j.lrr.2026.100561
Jordan Rubenstein, Sarah M. Schwartz, Jay Vankawala, Michael Caplan, Steven Shea, Joseph G. Jurcic
Imatinib, a tyrosine kinase inhibitor used for chronic myeloid leukemia (CML) and gastrointestinal stromal tumors (GIST), is associated with myalgia and creatine kinase (CK) elevations, though severe rhabdomyolysis and myopathy are rare. We report an 83-year-old woman with CML who developed progressive proximal weakness, dark urine, and acute kidney injury after three years of imatinib therapy. Laboratory evaluation revealed CK >24,000 U/L, transaminitis, and myoglobinuria. MRI showed diffuse muscle and fascial edema, while autoimmune testing was negative. Imatinib and rosuvastatin were discontinued, and the patient was managed with intravenous fluids and supportive care. CK and renal function normalized within 10 days, with substantial recovery of strength. The strong temporal relationship between drug withdrawal and improvement implicates imatinib as the etiology. This case represents one of the most severe reported instances of imatinib-induced rhabdomyolysis. Early recognition and discontinuation are essential to prevent life-threatening sequelae.
{"title":"Imatinib-induced rhabdomyolysis: A case report","authors":"Jordan Rubenstein, Sarah M. Schwartz, Jay Vankawala, Michael Caplan, Steven Shea, Joseph G. Jurcic","doi":"10.1016/j.lrr.2026.100561","DOIUrl":"10.1016/j.lrr.2026.100561","url":null,"abstract":"<div><div>Imatinib, a tyrosine kinase inhibitor used for chronic myeloid leukemia (CML) and gastrointestinal stromal tumors (GIST), is associated with myalgia and creatine kinase (CK) elevations, though severe rhabdomyolysis and myopathy are rare. We report an 83-year-old woman with CML who developed progressive proximal weakness, dark urine, and acute kidney injury after three years of imatinib therapy. Laboratory evaluation revealed CK >24,000 U/L, transaminitis, and myoglobinuria. MRI showed diffuse muscle and fascial edema, while autoimmune testing was negative. Imatinib and rosuvastatin were discontinued, and the patient was managed with intravenous fluids and supportive care. CK and renal function normalized within 10 days, with substantial recovery of strength. The strong temporal relationship between drug withdrawal and improvement implicates imatinib as the etiology. This case represents one of the most severe reported instances of imatinib-induced rhabdomyolysis. Early recognition and discontinuation are essential to prevent life-threatening sequelae.</div></div>","PeriodicalId":38435,"journal":{"name":"Leukemia Research Reports","volume":"25 ","pages":"Article 100561"},"PeriodicalIF":0.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145977082","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 : 2026-01-01DOI: 10.1016/j.lrr.2026.100562
Wenwen Zhang , Bin Luo , Zhuo Liu , Jie Mi , Yanping Yang , Yuan Li
This study analyzed FAERS data to evaluate pegaspargase safety in pediatric acute lymphoblastic leukemia treatment. Among 21,161,817 reports, 847 identified pegaspargase as the primary suspect drug, revealing adverse events (AEs) across 26 organ systems. Disproportionality analysis identified four previously unlisted AEs. Critically, pegaspargase-associated pancreatitis incidence showed significant age-dependence (χ²=8.219, p < 0.05). These findings address the knowledge gap in real-world, long-term pediatric safety profiles and provide crucial clinical references for safer medication use in children.
{"title":"Pancreatitis induced by Peg-aspargase in children: a real-world pharmacovigilance analysis based on FDA Adverse Event Reporting System (FAERS)","authors":"Wenwen Zhang , Bin Luo , Zhuo Liu , Jie Mi , Yanping Yang , Yuan Li","doi":"10.1016/j.lrr.2026.100562","DOIUrl":"10.1016/j.lrr.2026.100562","url":null,"abstract":"<div><div>This study analyzed FAERS data to evaluate pegaspargase safety in pediatric acute lymphoblastic leukemia treatment. Among 21,161,817 reports, 847 identified pegaspargase as the primary suspect drug, revealing adverse events (AEs) across 26 organ systems. Disproportionality analysis identified four previously unlisted AEs. Critically, pegaspargase-associated pancreatitis incidence showed significant age-dependence (χ²=8.219, <em>p</em> < 0.05). These findings address the knowledge gap in real-world, long-term pediatric safety profiles and provide crucial clinical references for safer medication use in children.</div></div>","PeriodicalId":38435,"journal":{"name":"Leukemia Research Reports","volume":"25 ","pages":"Article 100562"},"PeriodicalIF":0.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145977079","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 : 2026-01-01DOI: 10.1016/j.lrr.2026.100564
Tristan Meier , Giovann Huynh , Ernesto Ayala , Han W. Tun , Madiha Iqbal
Richter’s syndrome (RS) is characterized by transformation of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) into an aggressive lymphoma. While significant treatment advances have been made in the management of CLL/SLL, current front-line management of RS is consistent with chemoimmunotherapy (CIT), a therapeutic approach adopted from the management of de-novo diffuse large B-cell lymphoma (DLBCL). In de-novo DLBCL, CIT alone can potentially cure a significant percentage of patients; however in RS, outcomes with CIT alone are particularly poor. Therefore there is a significant unmet need to improve the current standard of care for the management of RS. We present a case of a patient with newly diagnosed RS who was treated with a novel upfront combination of CIT and a Bruton tyrosine kinase inhibitor, resulting in excellent long-term outcomes. We also present accompanying literature review highlighting other anecdotal cases reported with similar therapeutic approach and discuss emerging treatment strategies in the management of RS.
{"title":"Bruton tyrosine kinase inhibitors in combination with chemoimmunotherapy is an effective treatment for patients with Richter’s syndrome","authors":"Tristan Meier , Giovann Huynh , Ernesto Ayala , Han W. Tun , Madiha Iqbal","doi":"10.1016/j.lrr.2026.100564","DOIUrl":"10.1016/j.lrr.2026.100564","url":null,"abstract":"<div><div>Richter’s syndrome (RS) is characterized by transformation of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) into an aggressive lymphoma. While significant treatment advances have been made in the management of CLL/SLL, current front-line management of RS is consistent with chemoimmunotherapy (CIT), a therapeutic approach adopted from the management of de-novo diffuse large B-cell lymphoma (DLBCL). In de-novo DLBCL, CIT alone can potentially cure a significant percentage of patients; however in RS, outcomes with CIT alone are particularly poor. Therefore there is a significant unmet need to improve the current standard of care for the management of RS. We present a case of a patient with newly diagnosed RS who was treated with a novel upfront combination of CIT and a Bruton tyrosine kinase inhibitor, resulting in excellent long-term outcomes. We also present accompanying literature review highlighting other anecdotal cases reported with similar therapeutic approach and discuss emerging treatment strategies in the management of RS.</div></div>","PeriodicalId":38435,"journal":{"name":"Leukemia Research Reports","volume":"25 ","pages":"Article 100564"},"PeriodicalIF":0.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145977083","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}
Follicular lymphoma (FL) is the second most common subtype of non-Hodgkin lymphoma (NHL) and comprises 9 % of total NHL in India. Rituximab maintenance (RM) after induction immunochemotherapy improves PFS. However, currently, no data exists from the Indian continent regarding the impact of Rituximab maintenance (RM) on overall survival (OS) & progression-free survival (PFS). Our study aims to assess if RM improves the outcomes in FL patients.
Methods
This retrospective study included 95 patients diagnosed with FL meeting GELF criteria and registered at our institute All India Institute of Medical Sciences Delhi between January 2012 -December 2023. Among these, forty -four (46 %) patients received 2 years of RM every 2 months after induction immunochemotherapy. The primary outcome were overall survival (OS) and progression-free survival. Secondary outcomes were factors affecting OS & PFS.
Results
Out of the 95 patients who met GELF criteria, 52 were male and 43 were female, with a median age of 53 years (range: 27–81). Advanced Ann Arbor stage III/IV comprises 82 (86 %) patients. Bone marrow involvement and bulky disease were observed in 36 (38 %) and 29 (31 %) patients respectively. Based on the Follicular Lymphoma International Prognostic Index (FLIPI-1), 27 (28 %) were low risk, 9 (10 %) intermediate risk, and 59 (62 %) were high risk. The complete remission (CR) was achieved in 71 % of patients. During follow-up, 27 (28 %) patients experienced relapsed and 8 patients transformed to diffuse large B-cell lymphoma (DLBCL). At a median follow-up of 63 months, the median OS was not reached. The median PFS was 122 months in the RM group and 94 months in the non-RM group, with 5-year PFS of 91.6 % vs 59.3 %, respectively (log-rank p = 0.017). Rituximab maintenance was independently associated with improved PFS (adjusted HR 0.28, 95 % CI: 0.12–0.65, p = 0.003). Failure to attain CR (aHR 2.49, 95 % CI: 1.20–5.19, p = 0.015) and bone marrow involvement (aHR 2.92, 95 % CI: 0.99–8.63, p = 0.05) were independently associated with inferior PFS.
Conclusions
Rituximab maintenance after induction immunochemotherapy significantly improved PFS. This is the first study from India demonstrating the impact of rituximab maintenance in FL.
滤泡性淋巴瘤（FL）是第二常见的非霍奇金淋巴瘤（NHL）亚型，占印度NHL总数的9%。诱导免疫化疗后利妥昔单抗维持（RM）改善PFS。然而，目前还没有来自印度大陆的关于利妥昔单抗维持（RM）对总生存期（OS）和无进展生存期（PFS）影响的数据。我们的研究旨在评估RM是否能改善FL患者的预后。方法回顾性研究纳入2012年1月至2023年12月在我们研究所全印度医学科学研究所登记的95例符合GELF标准的FL患者。其中，44例（46%）患者在诱导免疫化疗后每2个月接受2年的化疗。主要终点是总生存期（OS）和无进展生存期。次要结局是影响OS和PFS的因素。结果95例符合GELF标准的患者中，男性52例，女性43例，中位年龄53岁（范围：27-81岁）。晚期安娜堡III/IV期包括82例（86%）患者。骨髓受累36例（38%），大面积病变29例（31%）。根据滤泡性淋巴瘤国际预后指数（FLIPI-1）， 27例（28%）为低危，9例（10%）为中危，59例（62%）为高危。71%的患者达到完全缓解（CR）。在随访期间，27例（28%）患者复发，8例转化为弥漫性大b细胞淋巴瘤（DLBCL）。在中位随访63个月时，中位OS未达到。RM组和非RM组的中位PFS分别为122个月和94个月，5年PFS分别为91.6%和59.3% （log-rank p = 0.017）。利妥昔单抗维持与PFS改善独立相关（调整后危险度0.28,95% CI: 0.12-0.65, p = 0.003）。未能达到CR （aHR 2.49, 95% CI: 1.20 ~ 5.19, p = 0.015）和骨髓受累（aHR 2.92, 95% CI: 0.99 ~ 8.63, p = 0.05）与PFS较差独立相关。结论诱导免疫化疗后维持斯利妥昔单抗可显著改善PFS。这是印度第一个证明利妥昔单抗维持对FL影响的研究。
{"title":"Impact of Rituximab Maintenance on outcomes in Follicular Lymphoma: An indian experience","authors":"Harish Pant , Ajay Gogia , Atul Sharma , Naveet Wig , Hari Krishna Raju Sagiraju , Saumyaranjan Mallick , Ritu Gupta , Ahitagni Biswas","doi":"10.1016/j.lrr.2025.100554","DOIUrl":"10.1016/j.lrr.2025.100554","url":null,"abstract":"<div><h3>Background</h3><div>Follicular lymphoma (FL) is the second most common subtype of non-Hodgkin lymphoma (NHL) and comprises 9 % of total NHL in India. Rituximab maintenance (RM) after induction immunochemotherapy improves PFS. However, currently, no data exists from the Indian continent regarding the impact of Rituximab maintenance (RM) on overall survival (OS) & progression-free survival (PFS). Our study aims to assess if RM improves the outcomes in FL patients.</div></div><div><h3>Methods</h3><div>This retrospective study included 95 patients diagnosed with FL meeting GELF criteria and registered at our institute All India Institute of Medical Sciences Delhi between January 2012 -December 2023. Among these, forty -four (46 %) patients received 2 years of RM every 2 months after induction immunochemotherapy. The primary outcome were overall survival (OS) and progression-free survival. Secondary outcomes were factors affecting OS & PFS.</div></div><div><h3>Results</h3><div>Out of the 95 patients who met GELF criteria, 52 were male and 43 were female, with a median age of 53 years (range: 27–81). Advanced Ann Arbor stage III/IV comprises 82 (86 %) patients. Bone marrow involvement and bulky disease were observed in 36 (38 %) and 29 (31 %) patients respectively. Based on the Follicular Lymphoma International Prognostic Index (FLIPI-1), 27 (28 %) were low risk, 9 (10 %) intermediate risk, and 59 (62 %) were high risk. The complete remission (CR) was achieved in 71 % of patients. During follow-up, 27 (28 %) patients experienced relapsed and 8 patients transformed to diffuse large B-cell lymphoma (DLBCL). At a median follow-up of 63 months, the median OS was not reached. The median PFS was 122 months in the RM group and 94 months in the non-RM group, with 5-year PFS of 91.6 % vs 59.3 %, respectively (log-rank <em>p</em> = 0.017). Rituximab maintenance was independently associated with improved PFS (adjusted HR 0.28, 95 % CI: 0.12–0.65, <em>p</em> = 0.003). Failure to attain CR (aHR 2.49, 95 % CI: 1.20–5.19, <em>p</em> = 0.015) and bone marrow involvement (aHR 2.92, 95 % CI: 0.99–8.63, <em>p</em> = 0.05) were independently associated with inferior PFS.</div></div><div><h3>Conclusions</h3><div>Rituximab maintenance after induction immunochemotherapy significantly improved PFS. This is the first study from India demonstrating the impact of rituximab maintenance in FL.</div></div>","PeriodicalId":38435,"journal":{"name":"Leukemia Research Reports","volume":"25 ","pages":"Article 100554"},"PeriodicalIF":0.9,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145692159","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 : 2025-11-25DOI: 10.1016/j.lrr.2025.100553
Yanyan Qiu, Huarong Zhou, Shaoyuan Wang
Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia characterized by the promyelocytic leukemia-retinoic acid receptor alpha (PML-RARA) fusion gene and exceptional responsiveness to differentiation therapy with all-trans retinoic acid (ATRA) and arsenic trioxide (Arsenic Trioxide). However, rare variant forms of APL involving alternative RARA fusion partners, such as FIP1L1-RARA, are typically resistant to ATRA/ATO-based regimens and are associated with poor clinical outcomes. We report a rare case of FIP1L1-RARA-positive APL in a patient who initially presented with clinical, morphological, and immunophenotypic features consistent with classical APL. Standard diagnostic evaluations, including morphology, flow cytometry, and fluorescence in situ hybridization (FISH), failed to detect the fusion abnormality. The diagnosis was ultimately confirmed by RNA sequencing (RNA-Seq). Empirical induction with ATRA and ATO was initiated but resulted in persistent and progressive promyelocytosis. Anthracycline-based chemotherapy was subsequently administered, followed by azacitidine combined with venetoclax in the subsequent course of treatment. Although partial hematologic improvement was observed, the overall response remained suboptimal. This case underscores the diagnostic challenges of atypical APL and highlights the pivotal role of RNA-Seq in identifying cryptic RARA rearrangements. A literature review suggests that FIP1L1-RARA-positive APL represents a biologically and clinically distinct entity with highly variable treatment responses and poor prognosis. Early molecular diagnosis and prompt implementation of conventional chemotherapy or targeted therapies such as venetoclax may be essential to improving outcomes in this rare APL subtype.
{"title":"A rare case of variant acute promyelocytic leukemia with FIP1L1-RARA fusion gene: case report and literature review","authors":"Yanyan Qiu, Huarong Zhou, Shaoyuan Wang","doi":"10.1016/j.lrr.2025.100553","DOIUrl":"10.1016/j.lrr.2025.100553","url":null,"abstract":"<div><div>Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia characterized by the promyelocytic leukemia-retinoic acid receptor alpha (<em>PML-RARA</em>) fusion gene and exceptional responsiveness to differentiation therapy with all-trans retinoic acid (ATRA) and arsenic trioxide (Arsenic Trioxide). However, rare variant forms of APL involving alternative <em>RARA</em> fusion partners, such as <em>FIP1L1-RARA</em>, are typically resistant to ATRA/ATO-based regimens and are associated with poor clinical outcomes. We report a rare case of <em>FIP1L1-RARA</em>-positive APL in a patient who initially presented with clinical, morphological, and immunophenotypic features consistent with classical APL. Standard diagnostic evaluations, including morphology, flow cytometry, and fluorescence in situ hybridization (FISH), failed to detect the fusion abnormality. The diagnosis was ultimately confirmed by RNA sequencing (RNA-Seq). Empirical induction with ATRA and ATO was initiated but resulted in persistent and progressive promyelocytosis. Anthracycline-based chemotherapy was subsequently administered, followed by azacitidine combined with venetoclax in the subsequent course of treatment. Although partial hematologic improvement was observed, the overall response remained suboptimal. This case underscores the diagnostic challenges of atypical APL and highlights the pivotal role of RNA-Seq in identifying cryptic <em>RARA</em> rearrangements. A literature review suggests that <em>FIP1L1-RARA</em>-positive APL represents a biologically and clinically distinct entity with highly variable treatment responses and poor prognosis. Early molecular diagnosis and prompt implementation of conventional chemotherapy or targeted therapies such as venetoclax may be essential to improving outcomes in this rare APL subtype.</div></div>","PeriodicalId":38435,"journal":{"name":"Leukemia Research Reports","volume":"25 ","pages":"Article 100553"},"PeriodicalIF":0.9,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145625109","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}
Chronic Myeloid Leukemia (CML) is characterized by aberrant BCR::ABL1 tyrosine kinase activity in hematopoietic stem cells. Although tyrosine kinase inhibitors (TKIs) have revolutionized CML treatment, resistance remains a major clinical challenge. This review provides a comprehensive overview of CML, including its epidemiology, pathophysiology, diagnosis, and treatment, as outlined in the latest WHO consensus classification. Current treatment paradigms and the prospects for treatment-free remission (TFR) are also explored. The primary focus is on elucidating the molecular mechanisms of TKI resistance, emphasizing both well-known pathways such as PI3K/AKT, MAPK, JAK/STAT, and alternative pathways including SRC/AKT. This review stands out by integrating recent discoveries regarding genetic mutations within the BCR::ABL1 gene, alongside other molecular alterations contributing to resistance. By synthesizing this knowledge, it aims to guide clinical practitioners, investigators, and translational researchers in developing innovative strategies to overcome resistance and improve patient outcomes in CML.
{"title":"Mechanisms and signaling pathways of tyrosine kinase inhibitor resistance in chronic myeloid leukemia: A comprehensive review.","authors":"Meriem Lahmouad, Zahrae Rachid, Rawane Bellemrrabet, Jihane Zerrouk, Khan Wen Goh, Abdelhakim Bouyahya, Youssef Aboussalah","doi":"10.1016/j.lrr.2025.100533","DOIUrl":"10.1016/j.lrr.2025.100533","url":null,"abstract":"<p><p>Chronic Myeloid Leukemia (CML) is characterized by aberrant BCR::ABL1 tyrosine kinase activity in hematopoietic stem cells. Although tyrosine kinase inhibitors (TKIs) have revolutionized CML treatment, resistance remains a major clinical challenge. This review provides a comprehensive overview of CML, including its epidemiology, pathophysiology, diagnosis, and treatment, as outlined in the latest WHO consensus classification. Current treatment paradigms and the prospects for treatment-free remission (TFR) are also explored. The primary focus is on elucidating the molecular mechanisms of TKI resistance, emphasizing both well-known pathways such as PI3K/AKT, MAPK, JAK/STAT, and alternative pathways including SRC/AKT. This review stands out by integrating recent discoveries regarding genetic mutations within the BCR::ABL1 gene, alongside other molecular alterations contributing to resistance. By synthesizing this knowledge, it aims to guide clinical practitioners, investigators, and translational researchers in developing innovative strategies to overcome resistance and improve patient outcomes in CML.</p>","PeriodicalId":38435,"journal":{"name":"Leukemia Research Reports","volume":"24 ","pages":"100533"},"PeriodicalIF":0.9,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12355124/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144875742","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.2025.100512
Phu Chi Dung , Huynh Duc Vinh Phu , Cao Van Dong , Chau Thuy Ha , Nguyen Thi Thanh Ha , Tran Ngoc Xuan Thy , Le Vu Ha Thanh , Huynh Nghia , Nguyen Tan Binh , Hoang Anh Vu , Phan Thi Xinh , Cao Sy Luan
Background
BCR::ABL1 kinase domain (KD) mutations represent a common cause of resistance to tyrosine kinase inhibitors in chronic myeloid leukemia (CML) patients. The frequency and pattern of KD mutations differ among populations worldwide. However, the characteristics of KD mutations in Vietnamese patients remain unclear.
Methods
A retrospective cohort study of CML patients at Blood Transfusion Hematology Hospital who were resistant to frontline imatinib between Oct 2010 and Oct 2018. Direct sequencing technique was performed to detect KD mutations.
Results
488 imatinib-resistant CML patients were included in our study. The median age of the patients was 39, with the majority (82.1 %) diagnosed with chronic phase at the time of resistance. KD mutations were identified in 173 (35.5 %) patients, with 8 cases involving novel variants. The KD mutations predominantly localized within the P-loop of BCR::ABL1 (36.7 %). G250E was the most common mutation, followed by Y253H, M351T, and M244V. In particular, Y253H, T315I, F359V, F317L, E355G, and Q252H were frequently observed in accelerated phase and blast crisis patients. In addition, M244V, T315I, E459K, E255K, F317L, Q252H and E355G were all observed in primary resistant patients.
Conclusion
The emergence of certain specific mutations may serve as the early indicators of leukemic progression, necessitating prompt intervention for better disease control.
{"title":"Characteristics of BCR::ABL1 kinase domain mutations in Vietnamese chronic myeloid leukemia patients","authors":"Phu Chi Dung , Huynh Duc Vinh Phu , Cao Van Dong , Chau Thuy Ha , Nguyen Thi Thanh Ha , Tran Ngoc Xuan Thy , Le Vu Ha Thanh , Huynh Nghia , Nguyen Tan Binh , Hoang Anh Vu , Phan Thi Xinh , Cao Sy Luan","doi":"10.1016/j.lrr.2025.100512","DOIUrl":"10.1016/j.lrr.2025.100512","url":null,"abstract":"<div><h3>Background</h3><div><em>BCR::ABL1</em> kinase domain (KD) mutations represent a common cause of resistance to tyrosine kinase inhibitors in chronic myeloid leukemia (CML) patients. The frequency and pattern of KD mutations differ among populations worldwide. However, the characteristics of KD mutations in Vietnamese patients remain unclear.</div></div><div><h3>Methods</h3><div>A retrospective cohort study of CML patients at Blood Transfusion Hematology Hospital who were resistant to frontline imatinib between Oct 2010 and Oct 2018. Direct sequencing technique was performed to detect KD mutations.</div></div><div><h3>Results</h3><div>488 imatinib-resistant CML patients were included in our study. The median age of the patients was 39, with the majority (82.1 %) diagnosed with chronic phase at the time of resistance. KD mutations were identified in 173 (35.5 %) patients, with 8 cases involving novel variants. The KD mutations predominantly localized within the P-loop of BCR::ABL1 (36.7 %). G250E was the most common mutation, followed by Y253H, M351T, and M244V. In particular, Y253H, T315I, F359V, F317L, E355G, and Q252H were frequently observed in accelerated phase and blast crisis patients. In addition, M244V, T315I, E459K, E255K, F317L, Q252H and E355G were all observed in primary resistant patients.</div></div><div><h3>Conclusion</h3><div>The emergence of certain specific mutations may serve as the early indicators of leukemic progression, necessitating prompt intervention for better disease control.</div></div>","PeriodicalId":38435,"journal":{"name":"Leukemia Research Reports","volume":"23 ","pages":"Article 100512"},"PeriodicalIF":0.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143887379","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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