Pub Date : 2026-01-08DOI: 10.1016/j.leukres.2026.108166
Ani Bilanishvili , Tamar Tsertsvadze , Kurtis Edwards , Sarah John-Olabode , Uzma Syed , Irina Datikashvili-David , Emanuela V. Volpi , John Murphy , Peter M. Lydyard , Nina Porakishvili
Chronic lymphocytic leukaemia (CLL) progression is critically dependent on tumour microenvironment (TME) signals, including those regulated via toll-like receptors (TLRs) that drive CLL cell survival and proliferation. We have previously shown that CD180, an orphan TLR is expressed on the surface in approximately 60 % of CLL samples, and that heterogeneity of CD180 cell surface expression and signalling impacts CLL cell survival, proliferation, and apoptosis. Interleukin-4 (IL-4), a cytokine abundantly present in the CLL microenvironment, is a well-documented pro-survival factor for CLL cells. IL-4 has also been shown to enhance sIgM expression and function by subsequent downstream signalling in a JAK3/STAT6 dependent manner within CLL samples. In this study, we investigated the impact of IL-4 on CD180 expression, CD180-mediated signalling and apoptosis of CLL cells and cell lines MEC-1 and RAMOS. Our results demonstrate that IL-4 enhances CD180 surface expression in CLL cells and RAMOS cell line, affecting downstream signalling pathways that alter CLL cell survival through the activation of AKT and p38MAPK. MEC-1 cells exhibited a less pronounced and variable response. These findings highlight the IL-4/CD180 axis as an important modulator of CLL, altering cell signalling dynamics.
{"title":"The effect of IL-4 on CD180 expression and signalling in Chronic lymphocytic leukaemia (CLL)","authors":"Ani Bilanishvili , Tamar Tsertsvadze , Kurtis Edwards , Sarah John-Olabode , Uzma Syed , Irina Datikashvili-David , Emanuela V. Volpi , John Murphy , Peter M. Lydyard , Nina Porakishvili","doi":"10.1016/j.leukres.2026.108166","DOIUrl":"10.1016/j.leukres.2026.108166","url":null,"abstract":"<div><div>Chronic lymphocytic leukaemia (CLL) progression is critically dependent on tumour microenvironment (TME) signals, including those regulated via toll-like receptors (TLRs) that drive CLL cell survival and proliferation. We have previously shown that CD180, an orphan TLR is expressed on the surface in approximately 60 % of CLL samples, and that heterogeneity of CD180 cell surface expression and signalling impacts CLL cell survival, proliferation, and apoptosis. Interleukin-4 (IL-4), a cytokine abundantly present in the CLL microenvironment, is a well-documented pro-survival factor for CLL cells. IL-4 has also been shown to enhance sIgM expression and function by subsequent downstream signalling in a JAK3/STAT6 dependent manner within CLL samples. In this study, we investigated the impact of IL-4 on CD180 expression, CD180-mediated signalling and apoptosis of CLL cells and cell lines MEC-1 and RAMOS. Our results demonstrate that IL-4 enhances CD180 surface expression in CLL cells and RAMOS cell line, affecting downstream signalling pathways that alter CLL cell survival through the activation of AKT and p38MAPK. MEC-1 cells exhibited a less pronounced and variable response. These findings highlight the IL-4/CD180 axis as an important modulator of CLL, altering cell signalling dynamics.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"161 ","pages":"Article 108166"},"PeriodicalIF":2.2,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145981906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-08DOI: 10.1016/j.leukres.2025.108154
Maya A Stern, Elizaveta Klekovkina, Stephanie M Nanos, Esme Fuller-Thomson, Carmine Malfitano
Purpose: Caregiver burden is an often reported consequence of caring for patients with acute leukemia (AL). The current literature extensively describes caregiving tasks for patients with AL but provides limited information about the challenge of balancing these new obligations with previous and concurrent personal and family responsibilities. The goal of this qualitative study was to understand the multifaceted responsibilities of caregivers of patients with AL, their perceived impact, and the available resources that these caregivers found to be supportive in their caregiving role.
Methods: A secondary analysis, using qualitative description, was conducted on data obtained from interviews with 21 caregivers of children and adults with AL.
Results: Caregivers described balancing many responsibilities related to the patient, other relationships, work, and home. Coordinating and multitasking responsibilities were perceived to have an adverse effect on the emotional, physical, and financial well-being of participants. Social support was identified as a resource that supported the ability to manage the diverse responsibilities, and caregivers provided emotional and practical suggestions for care.
Conclusions: Upon becoming a caregiver for a patient with AL, individuals are faced with new responsibilities that compound their existing obligations, often resulting in the de-prioritization of the caregiver's needs and other responsibilities. The development and implementation of caregiver support as a standard of care is necessary to mitigate the negative consequences of caregiving.
{"title":"Juggling two worlds: Exploring the experiences of caregivers of patients with acute leukemia.","authors":"Maya A Stern, Elizaveta Klekovkina, Stephanie M Nanos, Esme Fuller-Thomson, Carmine Malfitano","doi":"10.1016/j.leukres.2025.108154","DOIUrl":"https://doi.org/10.1016/j.leukres.2025.108154","url":null,"abstract":"<p><strong>Purpose: </strong>Caregiver burden is an often reported consequence of caring for patients with acute leukemia (AL). The current literature extensively describes caregiving tasks for patients with AL but provides limited information about the challenge of balancing these new obligations with previous and concurrent personal and family responsibilities. The goal of this qualitative study was to understand the multifaceted responsibilities of caregivers of patients with AL, their perceived impact, and the available resources that these caregivers found to be supportive in their caregiving role.</p><p><strong>Methods: </strong>A secondary analysis, using qualitative description, was conducted on data obtained from interviews with 21 caregivers of children and adults with AL.</p><p><strong>Results: </strong>Caregivers described balancing many responsibilities related to the patient, other relationships, work, and home. Coordinating and multitasking responsibilities were perceived to have an adverse effect on the emotional, physical, and financial well-being of participants. Social support was identified as a resource that supported the ability to manage the diverse responsibilities, and caregivers provided emotional and practical suggestions for care.</p><p><strong>Conclusions: </strong>Upon becoming a caregiver for a patient with AL, individuals are faced with new responsibilities that compound their existing obligations, often resulting in the de-prioritization of the caregiver's needs and other responsibilities. The development and implementation of caregiver support as a standard of care is necessary to mitigate the negative consequences of caregiving.</p>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":" ","pages":"108154"},"PeriodicalIF":2.2,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145944894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","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.leukres.2025.108156
Yujin Jung , Su Sung Kim , Sooyong Park , Dajeong Jeong , Ja-Yoon Gu , Jee-Soo Lee , Seon Young Kim , Yoon Hwan Chang , Moon-Woo Seong , Hongseok Yun , Hyun Kyung Kim
Background
Myelodysplastic neoplasms (MDS) are occasionally accompanied by bone marrow (BM) eosinophilia or basophilia. This study investigated molecular and cytogenetic characteristics and clinical implications of MDS with BM eosinophilia or basophilia as well as their prevalence.
Methods
A total of 464 MDS patients were evaluated for prevalence of BM eosinophilia or basophilia. A total of 74 MDS patients were included in the next-generation sequencing (NGS) testing, which was conducted on 90 candidate genes frequently found in hematologic malignancies. Fourteen patients exhibited BM eosinophilia (MDS-EOS), six patients displayed BM basophilia (MDS-BASO), fifty-five patients did not demonstrate eosinophilia or basophilia (MDS-/-), and only one satisfied both MDS-EOS and MDS-BASO. Cytogenetic abnormalities and overall survival were also investigated.
Results
MDS with BM eosinophilia or basophilia were observed in 7.33 % or 4.09 % of patients, respectively. MDS-EOS revealed significantly higher frequencies of mutations in ATM, TP53, CEBPA, FLT3 and DNA damage response (DDR) genes (ATM, PPM1D and TP53 combined). In MDS-BASO, significantly higher frequencies of mutations in ASXL1 and U2AF1 were shown. Variant allele frequency of DDR gene mutations significantly correlated with increased BM eosinophil fraction. Significant frequency of complex chromosomal abnormalities, especially involving chromosomes 5 and 7, was found in both MDS-EOS and MDS-BASO. MDS-EOS demonstrated significantly poorer survival rates than MDS-/-.
Conclusion
BM eosinophilia or basophilia was not uncommon. MDS with BM eosinophilia exhibited distinct mutational profiles including DDR genes mutations, which may attribute to adverse clinical outcomes. Identification of these subtypes can aid in prognosis and potentially guide targeted therapeutic approaches.
{"title":"Genomic profiles of myelodysplastic neoplasm with bone marrow eosinophilia or basophilia: Inflammatory drivers and DNA damage response","authors":"Yujin Jung , Su Sung Kim , Sooyong Park , Dajeong Jeong , Ja-Yoon Gu , Jee-Soo Lee , Seon Young Kim , Yoon Hwan Chang , Moon-Woo Seong , Hongseok Yun , Hyun Kyung Kim","doi":"10.1016/j.leukres.2025.108156","DOIUrl":"10.1016/j.leukres.2025.108156","url":null,"abstract":"<div><h3>Background</h3><div>Myelodysplastic neoplasms (MDS) are occasionally accompanied by bone marrow (BM) eosinophilia or basophilia. This study investigated molecular and cytogenetic characteristics and clinical implications of MDS with BM eosinophilia or basophilia as well as their prevalence.</div></div><div><h3>Methods</h3><div>A total of 464 MDS patients were evaluated for prevalence of BM eosinophilia or basophilia. A total of 74 MDS patients were included in the next-generation sequencing (NGS) testing, which was conducted on 90 candidate genes frequently found in hematologic malignancies. Fourteen patients exhibited BM eosinophilia (MDS-EOS), six patients displayed BM basophilia (MDS-BASO), fifty-five patients did not demonstrate eosinophilia or basophilia (MDS-/-), and only one satisfied both MDS-EOS and MDS-BASO. Cytogenetic abnormalities and overall survival were also investigated.</div></div><div><h3>Results</h3><div>MDS with BM eosinophilia or basophilia were observed in 7.33 % or 4.09 % of patients, respectively. MDS-EOS revealed significantly higher frequencies of mutations in <em>ATM, TP53, CEBPA, FLT3</em> and DNA damage response (DDR) genes (<em>ATM, PPM1D</em> and <em>TP53</em> combined). In MDS-BASO, significantly higher frequencies of mutations in <em>ASXL1</em> and <em>U2AF1</em> were shown. Variant allele frequency of DDR gene mutations significantly correlated with increased BM eosinophil fraction. Significant frequency of complex chromosomal abnormalities, especially involving chromosomes 5 and 7, was found in both MDS-EOS and MDS-BASO. MDS-EOS demonstrated significantly poorer survival rates than MDS-/-.</div></div><div><h3>Conclusion</h3><div>BM eosinophilia or basophilia was not uncommon. MDS with BM eosinophilia exhibited distinct mutational profiles including DDR genes mutations, which may attribute to adverse clinical outcomes. Identification of these subtypes can aid in prognosis and potentially guide targeted therapeutic approaches.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"160 ","pages":"Article 108156"},"PeriodicalIF":2.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145863067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-23DOI: 10.1016/j.leukres.2025.108150
Luisa Sisinni , Odelaisy León-Triana , Mikel Fernandez Artazcoz , Mauro Guariento , Iñigo Figueroa Real de Asua , Yasmina Mozo del Castillo , Paula Lazaro del Campo , David Bueno Sanchez , Carmen Mestre Durán , Jordi Minguillón Pedreño , Mercedes Gasior Kabat , Antonio Pérez-Martínez
We conducted a single-center retrospective analysis of 49 consecutive pediatric and AYA (adolescent and young adult) patients who underwent either T-cell receptor alpha/beta and CD19-depleted unrelated donor (URD) hematopoietic stem cell transplantation (HSCT) (TCRαβ/CD19-depleted URD HSCT; n = 22, including 13 matched unrelated donors [MUD] and 9 mismatched unrelated donors [MMUD]) or CD45RA⁺-depleted haploidentical (HAPLO) HSCT (CD45RA⁺-depleted HAPLO HSCT; n = 27) between 2018 and 2023 for malignant hematological disorders. Both groups showed comparable engraftment kinetics. Primary graft failure occurred in four patients (8.5 %), predominantly in the HAPLO group. Acute graft-versus-host disease (aGvHD) grade II–IV occurred in 72.9 % of patients, with the highest incidence in the MMUD subgroup (89 %; p = 0.03). Chronic GvHD (cGvHD) was observed in 42.6 % of patients, with a tendency toward a higher incidence in the MMUD group (67 % vs 38 % for MUD and 33 % for HAPLO; p = 0.08). The 2-year overall survival (OS) was 75.5 %, with no significant differences between groups (MUD 92.3 %, MMUD 77.7 %, HAPLO 66.6 %; p = 0.34). GvHD-free/relapse-free survival (GRFS) at 2 years favored MUD (51.9 %) and HAPLO (51.3 %) over MMUD (22.2 %), with significantly poorer GRFS in MMUD compared with HAPLO (p = 0.038). In multivariate analysis, disease status ≥ third complete remission (≥CR3) at HSCT was associated with significantly poorer OS (hazard ratio [HR] 13, 95 % confidence interval [CI] 1.2–130; p = 0.036), while sex mismatch (female donor to male recipient) was associated with inferior GRFS (HR 4.5, 95 % CI 1.6–12; p = 0.0035). Our results highlight the feasibility of both HAPLO and URD HSCT in children with malignancies, using distinct T-cell depletion strategies tailored to donor type. However, our findings also indicate that ex vivo T-cell depletion alone, without additional GvHD prophylaxis, is insufficient to prevent GvHD, underscoring the need for combined strategies to improve outcomes.
{"title":"Outcomes of two distinct T-cell depletion strategies in haploidentical vs unrelated donor pediatric HSCT: A single-center retrospective analysis","authors":"Luisa Sisinni , Odelaisy León-Triana , Mikel Fernandez Artazcoz , Mauro Guariento , Iñigo Figueroa Real de Asua , Yasmina Mozo del Castillo , Paula Lazaro del Campo , David Bueno Sanchez , Carmen Mestre Durán , Jordi Minguillón Pedreño , Mercedes Gasior Kabat , Antonio Pérez-Martínez","doi":"10.1016/j.leukres.2025.108150","DOIUrl":"10.1016/j.leukres.2025.108150","url":null,"abstract":"<div><div>We conducted a single-center retrospective analysis of 49 consecutive pediatric and AYA (adolescent and young adult) patients who underwent either T-cell receptor alpha/beta and CD19-depleted unrelated donor (URD) hematopoietic stem cell transplantation (HSCT) (TCRαβ/CD19-depleted URD HSCT; n = 22, including 13 matched unrelated donors [MUD] and 9 mismatched unrelated donors [MMUD]) or CD45RA⁺-depleted haploidentical (HAPLO) HSCT (CD45RA⁺-depleted HAPLO HSCT; n = 27) between 2018 and 2023 for malignant hematological disorders. Both groups showed comparable engraftment kinetics. Primary graft failure occurred in four patients (8.5 %), predominantly in the HAPLO group. Acute graft-versus-host disease (aGvHD) grade II–IV occurred in 72.9 % of patients, with the highest incidence in the MMUD subgroup (89 %; p = 0.03). Chronic GvHD (cGvHD) was observed in 42.6 % of patients, with a tendency toward a higher incidence in the MMUD group (67 % vs 38 % for MUD and 33 % for HAPLO; p = 0.08). The 2-year overall survival (OS) was 75.5 %, with no significant differences between groups (MUD 92.3 %, MMUD 77.7 %, HAPLO 66.6 %; p = 0.34). GvHD-free/relapse-free survival (GRFS) at 2 years favored MUD (51.9 %) and HAPLO (51.3 %) over MMUD (22.2 %), with significantly poorer GRFS in MMUD compared with HAPLO (p = 0.038). In multivariate analysis, disease status ≥ third complete remission (≥CR3) at HSCT was associated with significantly poorer OS (hazard ratio [HR] 13, 95 % confidence interval [CI] 1.2–130; p = 0.036), while sex mismatch (female donor to male recipient) was associated with inferior GRFS (HR 4.5, 95 % CI 1.6–12; p = 0.0035). Our results highlight the feasibility of both HAPLO and URD HSCT in children with malignancies, using distinct T-cell depletion strategies tailored to donor type. However, our findings also indicate that ex vivo T-cell depletion alone, without additional GvHD prophylaxis, is insufficient to prevent GvHD, underscoring the need for combined strategies to improve outcomes.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"160 ","pages":"Article 108150"},"PeriodicalIF":2.2,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145834238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-19DOI: 10.1016/j.leukres.2025.108149
Margarida Coucelo , Claudia Sargas , Rosa Ayala , María J. Larráyoz , María Carmen Chillón , Elena Soria , Cristina Bilbao , Esther Prados de la Torre , Maria Luis Amorim , Alberto Mirales , Antonia Cionfrini , Ana T. Simões , Ana C. Oliveira , Rebeca Rodríguez-Veiga , Pilar Lloret-Madrid , Yolanda Mendizábal , Carmen Botella , Teresa Bernal , Juan Bergua , Lorenzo Algarra , Eva Barragán
The rapid and accurate laboratory identification of targetable therapeutic genes, together with the implementation of measurable residual disease (MRD) based decision is essential for optimal clinical management in acute myeloid leukemia (AML). The PETHEMA (Programa Español de Tratamientos en Hematología) cooperative group comprises nine laboratories that perform centralized molecular studies by conventional PCR and Real-time quantitative PCR (RT-qPCR) for AML patients. With the aim to validate laboratories performances, we conducted three rounds of interlaboratory cross validation (ICV) for the quantification of CBFB::MYH11, RUNX1::RUNX1T1 and NPM1 and one round to determine the mutational status of NPM1, FLT3 (ITD and TKD2) IDH1 and IDH2. For RT-qPCR a total of 19 samples were tested and only 3 (15.8 %) failed to achieve 100 % concordance, corresponding to samples with low target gene mean ratios (ICV1-S4, ICV2-S1, ICV2-S6). For mutation detection in a total of 227 returned results, concordance rate ranged from 95 % to 100 %. FLT3-ITD and NPM1 mutation detection had 100 % concordant results. One false negative was reported for IDH2- R140 mutation and 4 false positives were detected: 2 FLT3-TKD2 and 2 IDH1-R132, likely reflecting differences in assay sensitivity. Overall, the results were highly satisfactory, particularly regarding MRD assessment, and highlighted key points for improvement, especially in baseline detection of FLT3-TKD2 and IDH1 mutations. This study represents the first collaborative initiative to evaluate performance of AML molecular targets within a laboratory network and underscores the importance of regular exercises to monitor performance, identify and resolve technical or interpretive discrepancies to ultimately ensure accurate clinical decision-making.
快速准确的实验室鉴定靶向治疗基因，以及基于可测量残留病（MRD）的决策的实施，对于急性髓性白血病（AML）的最佳临床管理至关重要。PETHEMA （Programa Español de Tratamientos en Hematología）合作小组由9个实验室组成，通过传统PCR和实时定量PCR （RT-qPCR）对AML患者进行集中的分子研究。为了验证实验室性能，我们进行了三轮实验室间交叉验证（ICV）来量化CBFB::MYH11、RUNX1::RUNX1T1和NPM1，并进行了一轮实验室间交叉验证（ICV）来确定NPM1、FLT3 (ITD和TKD2) IDH1和IDH2的突变状态。RT-qPCR共检测了19个样本，只有3个（15.8 %）未能达到100 %的一致性，对应于低靶基因平均比率的样本（ICV1-S4, ICV2-S1, ICV2-S6）。对于227个返回结果的突变检测，一致性率从95 %到100 %不等。FLT3-ITD与NPM1突变检测结果吻合度为100% %。报告了1例IDH2- R140突变假阴性和4例假阳性：2例FLT3-TKD2和2例IDH1-R132，可能反映了测定敏感性的差异。总体而言，结果非常令人满意，特别是在MRD评估方面，并强调了改进的关键点，特别是在FLT3-TKD2和IDH1突变的基线检测方面。该研究是首次在实验室网络中评估AML分子靶点表现的合作倡议，并强调了定期锻炼以监测表现、识别和解决技术或解释差异的重要性，最终确保准确的临床决策。
{"title":"Interlaboratory cross validation of acute myeloid leukemia fusion genes and mutational targets detected by PCR: Performance of PETHEMA central laboratories","authors":"Margarida Coucelo , Claudia Sargas , Rosa Ayala , María J. Larráyoz , María Carmen Chillón , Elena Soria , Cristina Bilbao , Esther Prados de la Torre , Maria Luis Amorim , Alberto Mirales , Antonia Cionfrini , Ana T. Simões , Ana C. Oliveira , Rebeca Rodríguez-Veiga , Pilar Lloret-Madrid , Yolanda Mendizábal , Carmen Botella , Teresa Bernal , Juan Bergua , Lorenzo Algarra , Eva Barragán","doi":"10.1016/j.leukres.2025.108149","DOIUrl":"10.1016/j.leukres.2025.108149","url":null,"abstract":"<div><div>The rapid and accurate laboratory identification of targetable therapeutic genes, together with the implementation of measurable residual disease (MRD) based decision is essential for optimal clinical management in acute myeloid leukemia (AML). The PETHEMA (Programa Español de Tratamientos en Hematología) cooperative group comprises nine laboratories that perform centralized molecular studies by conventional PCR and Real-time quantitative PCR (RT-qPCR) for AML patients. With the aim to validate laboratories performances, we conducted three rounds of interlaboratory cross validation (ICV) for the quantification of <em>CBFB::MYH11, RUNX1::RUNX1T1</em> and <em>NPM1</em> and one round to determine the mutational status of <em>NPM1</em>, <em>FLT3</em> (ITD and TKD2) <em>IDH1</em> and <em>IDH2</em>. For RT-qPCR a total of 19 samples were tested and only 3 (15.8 %) failed to achieve 100 % concordance, corresponding to samples with low target gene mean ratios (ICV1-S4, ICV2-S1, ICV2-S6). For mutation detection in a total of 227 returned results, concordance rate ranged from 95 % to 100 %. <em>FLT3</em>-ITD and <em>NPM1</em> mutation detection had 100 % concordant results. One false negative was reported for <em>IDH2</em>- R140 mutation and 4 false positives were detected: 2 <em>FLT3</em>-TKD2 and 2 <em>IDH1</em>-R132, likely reflecting differences in assay sensitivity. Overall, the results were highly satisfactory, particularly regarding MRD assessment, and highlighted key points for improvement, especially in baseline detection of <em>FLT3</em>-TKD2 and <em>IDH1</em> mutations. This study represents the first collaborative initiative to evaluate performance of AML molecular targets within a laboratory network and underscores the importance of regular exercises to monitor performance, identify and resolve technical or interpretive discrepancies to ultimately ensure accurate clinical decision-making.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"160 ","pages":"Article 108149"},"PeriodicalIF":2.2,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145827893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-19DOI: 10.1016/j.leukres.2025.108151
Carmen Stanganelli, Juana Cabrera, Andrea Bender, Evangelina Agriello, Davi Coe Torres, Gerson Moura Ferreira, Maria Paula Mota dos Santos, Eliana Saul Furquim Werneck Abdelhay, Irma Slavutsky
{"title":"Double IGHV rearrangements in a Latin American cohort of chronic lymphocytic leukemia patients","authors":"Carmen Stanganelli, Juana Cabrera, Andrea Bender, Evangelina Agriello, Davi Coe Torres, Gerson Moura Ferreira, Maria Paula Mota dos Santos, Eliana Saul Furquim Werneck Abdelhay, Irma Slavutsky","doi":"10.1016/j.leukres.2025.108151","DOIUrl":"10.1016/j.leukres.2025.108151","url":null,"abstract":"","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"160 ","pages":"Article 108151"},"PeriodicalIF":2.2,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145827879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-17DOI: 10.1016/j.leukres.2025.108155
Jiawang Ou , Jia Li , Qifa Liu , Hongsheng Zhou
Summary
RAS pathway alterations play an important role in the development and progression of hematological malignancies. However, their frequency and clinical significance in adult ALL remain poorly investigated and not well defined. In this study, we analyzed the frequency and prognostic significance of RAS pathway alterations in newly diagnosed adult ALL patients. Among the 387 patients, RAS pathway alterations were detected in 52 (13.4 %). Multivariate analysis identified these alterations as independent predictors of poor overall survival (OS) and event-free survival (EFS) (OS, P = 0.046; EFS, P = 0.004). Kaplan-Meier survival analysis revealed that patients with PTPN11 mutations had poorer OS (P = 0.029) than those without PTPN11 mutations. Patients with KRAS mutations had inferior OS and EFS compared to those without KRAS mutations (P = 0.021; 0.0017). These findings suggest that analysis of RAS pathway alterations may enable more accurate prognostic stratification of adult ALL patients.
RAS通路的改变在血液恶性肿瘤的发生和发展中起重要作用。然而，它们在成人ALL中的频率和临床意义仍然没有得到很好的研究和定义。在这项研究中，我们分析了RAS通路改变在新诊断的成人ALL患者中的频率和预后意义。在387例患者中，52例（13.4 %）检测到RAS通路改变。多变量分析发现，这些改变是总生存期（OS）和无事件生存期（EFS）较差的独立预测因子（OS, P = 0.046；EFS, P = 0.004）。Kaplan-Meier生存分析显示，PTPN11突变患者的OS较无PTPN11突变患者差（P = 0.029）。与未发生KRAS突变的患者相比，KRAS突变患者的OS和EFS较差（P = 0.021;0.0017）。这些发现表明，对RAS通路改变的分析可能使成人ALL患者的预后分层更加准确。
{"title":"Frequency and prognostic significance of RAS pathway alterations in adult acute lymphoblastic leukemia","authors":"Jiawang Ou , Jia Li , Qifa Liu , Hongsheng Zhou","doi":"10.1016/j.leukres.2025.108155","DOIUrl":"10.1016/j.leukres.2025.108155","url":null,"abstract":"<div><h3>Summary</h3><div><em>RAS</em> pathway alterations play an important role in the development and progression of hematological malignancies. However, their frequency and clinical significance in adult ALL remain poorly investigated and not well defined. In this study, we analyzed the frequency and prognostic significance of <em>RAS</em> pathway alterations in newly diagnosed adult ALL patients. Among the 387 patients, <em>RAS</em> pathway alterations were detected in 52 (13.4 %). Multivariate analysis identified these alterations as independent predictors of poor overall survival (OS) and event-free survival (EFS) (OS, <em>P</em> = 0.046; EFS, <em>P</em> = 0.004). Kaplan-Meier survival analysis revealed that patients with <em>PTPN11</em> mutations had poorer OS (<em>P</em> = 0.029) than those without <em>PTPN11</em> mutations. Patients with <em>KRAS</em> mutations had inferior OS and EFS compared to those without <em>KRAS</em> mutations (<em>P</em> = 0.021; 0.0017). These findings suggest that analysis of <em>RAS</em> pathway alterations may enable more accurate prognostic stratification of adult ALL patients.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"160 ","pages":"Article 108155"},"PeriodicalIF":2.2,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145827965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-16DOI: 10.1016/j.leukres.2025.108152
Ahmad Alhuraiji , Ayman Alhejazi , Bhausaheb Bagal , Chee Yen Lin , Efreen Montaño , Macarena Roa , Miguel Pavlovsky , Mohamed Samra , Shang-Ju Wu , Veena Selvaratnam , Ayman Elsayes , Mohamed Elsayed , Amgad Kamal , K. Pushpalata , Akemi Ishikawa , Francisco Gonzalez
Introduction
This study describes the clinical characteristics, treatment pathways, and resource utilisation of patients with chronic lymphocytic leukaemia (CLL) across multiple regions.
Methods
This retrospective, observational, registry-based study included patients diagnosed with CLL who started treatment for at least 12 months before data collection (November 2021 to March 2023). Patients were recruited from multiple centres across Asia, Australia, Latin America, and the Middle East and North Africa. A pilot cohort was included to describe the clinical characteristics of treatment-naïve CLL patients.
Results
The study included 886 patients in the CLL-treated and 123 in the treatment-naïve cohorts. The mean age was nearly 63 years in both cohorts, with a majority being male. There was low utilisation of risk scores (74–76.9 % of the patients had no available scores). The Rai staging showed that the majority of the treatment-naïve cohort was in stage 0 (60.6 %), while the CLL-treated cohort had a more even distribution across all stages. The Cumulative Illness Rating Scale score showed that 60.9 % of the CLL-treated cohort had a score of ≥ 6, compared to 58.5 % in the treatment-naïve cohort. The Fluorescence in situ hybridisation (FISH)-based prognosis was available for 41.2 % of the CLL-treated cohort and 56.9 % of the treatment-naïve cohort. The cytogenetic testing was available for only 18.7 % of the CLL-treated cohort. The chemoimmunotherapy (CIT) regimens were the most commonly prescribed regimen, with a median first-line progression-free survival (PFS) of 26.1 months (95 % CI: 13.8, 42.8). Targeted therapies in the first-line setting were used by 20.2 % of patients. For first-line therapy, the objective response rate for CIT was 53.2 % (95 % CI: 49.5 %, 57 %), compared to 56.4 % (95 % CI: 49.2 %, 63.7 %) for targeted therapies. Patients receiving CIT had significantly higher rates of adverse events, inpatient hospitalisations, longer hospital stays, and a greater need for blood transfusions.
Conclusion
The present global study demonstrates the regional variations in the presentation and outcomes of CLL. A considerable number of patients with CLL present with advanced disease staging at diagnosis; still, the utilisation of genetic testing is low despite the plethora of approved targeted therapy.
{"title":"Clinical characteristics, treatment pathway and resource utilisation for patients with chronic lymphocytic leukaemia: A multicentre retrospective study","authors":"Ahmad Alhuraiji , Ayman Alhejazi , Bhausaheb Bagal , Chee Yen Lin , Efreen Montaño , Macarena Roa , Miguel Pavlovsky , Mohamed Samra , Shang-Ju Wu , Veena Selvaratnam , Ayman Elsayes , Mohamed Elsayed , Amgad Kamal , K. Pushpalata , Akemi Ishikawa , Francisco Gonzalez","doi":"10.1016/j.leukres.2025.108152","DOIUrl":"10.1016/j.leukres.2025.108152","url":null,"abstract":"<div><h3>Introduction</h3><div>This study describes the clinical characteristics, treatment pathways, and resource utilisation of patients with chronic lymphocytic leukaemia (CLL) across multiple regions.</div></div><div><h3>Methods</h3><div>This retrospective, observational, registry-based study included patients diagnosed with CLL who started treatment for at least 12 months before data collection (November 2021 to March 2023). Patients were recruited from multiple centres across Asia, Australia, Latin America, and the Middle East and North Africa. A pilot cohort was included to describe the clinical characteristics of treatment-naïve CLL patients.</div></div><div><h3>Results</h3><div>The study included 886 patients in the CLL-treated and 123 in the treatment-naïve cohorts. The mean age was nearly 63 years in both cohorts, with a majority being male. There was low utilisation of risk scores (74–76.9 % of the patients had no available scores). The Rai staging showed that the majority of the treatment-naïve cohort was in stage 0 (60.6 %), while the CLL-treated cohort had a more even distribution across all stages. The Cumulative Illness Rating Scale score showed that 60.9 % of the CLL-treated cohort had a score of ≥ 6, compared to 58.5 % in the treatment-naïve cohort. The Fluorescence in situ hybridisation (FISH)-based prognosis was available for 41.2 % of the CLL-treated cohort and 56.9 % of the treatment-naïve cohort. The cytogenetic testing was available for only 18.7 % of the CLL-treated cohort. The chemoimmunotherapy (CIT) regimens were the most commonly prescribed regimen, with a median first-line progression-free survival (PFS) of 26.1 months (95 % CI: 13.8, 42.8). Targeted therapies in the first-line setting were used by 20.2 % of patients. For first-line therapy, the objective response rate for CIT was 53.2 % (95 % CI: 49.5 %, 57 %), compared to 56.4 % (95 % CI: 49.2 %, 63.7 %) for targeted therapies. Patients receiving CIT had significantly higher rates of adverse events, inpatient hospitalisations, longer hospital stays, and a greater need for blood transfusions.</div></div><div><h3>Conclusion</h3><div>The present global study demonstrates the regional variations in the presentation and outcomes of CLL. A considerable number of patients with CLL present with advanced disease staging at diagnosis; still, the utilisation of genetic testing is low despite the plethora of approved targeted therapy.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"160 ","pages":"Article 108152"},"PeriodicalIF":2.2,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145839659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-16DOI: 10.1016/j.leukres.2025.108153
Julian Ronnacker , Marc-Andre Urbahn , Christian Reicherts , Lina Kolloch , Philipp Berning , Andrew F. Berdel , Simon Call , Matthias Floeth , Julia Marx , Eva Eßeling , Jan-Henrik Mikesch , Christoph Schliemann , Hans Theodor Eich , Georg Lenz , Matthias Stelljes
Relapse treatment after allogeneic hematopoietic cell transplantation (HCT) for acute myeloid leukemia (AML) remains challenging. This retrospective single-center study investigates outcomes of AML patients transplanted with active disease who experienced relapse after HCT. We analyzed 67 patients who relapsed after HCT between 2014 and 2024. Patients were classified as having impending molecular relapse (n = 42, defined by persistent or recurrent genetic aberrations and/or a drop in CD34 + donor chimerism < 95 %) or overt hematologic relapse (n = 25). We evaluated overall survival (OS), relapse-free survival (RFS), and responses to relapse treatments. Thirty-seven (88 %) patients with impending relapse had a decrease in CD34+ donor chimerism; and only 5 (12 %) patients harbored an impending relapse without decrease in CD34+ donor chimerism. Two-year OS with impending relapse was 45 % (95 % confidence interval [CI], 31–64 %), with 13 of 23 patients (57 %) achieving measurable residual disease (MRD) negative remissions after donor lymphocyte infusions (DLI). RFS was significantly shorter in patients with impending relapse who did not receive DLI (hazard ratio [HR] 3.23, 95 % CI, 1.22–8.33, P = .02), whereas OS did not differ (HR 2.00, 95 % CI, 0.66–5.88; P = 0.22). Patients with overt relapse had poor outcomes with a 1-year survival of 24 % (95 % CI, 12–48 %). Our data underscore the importance of close follow-up after transplantation, especially in high-risk AML. Whenever relapse is imminent, timely immune-based therapy may induce durable MRD-negative remissions and was associated with improved RFS compared to hypomethylating agents without DLI in our cohort.
{"title":"Relapse after allogeneic hematopoietic stem cell transplantation in patients with active acute myeloid leukemia","authors":"Julian Ronnacker , Marc-Andre Urbahn , Christian Reicherts , Lina Kolloch , Philipp Berning , Andrew F. Berdel , Simon Call , Matthias Floeth , Julia Marx , Eva Eßeling , Jan-Henrik Mikesch , Christoph Schliemann , Hans Theodor Eich , Georg Lenz , Matthias Stelljes","doi":"10.1016/j.leukres.2025.108153","DOIUrl":"10.1016/j.leukres.2025.108153","url":null,"abstract":"<div><div>Relapse treatment after allogeneic hematopoietic cell transplantation (HCT) for acute myeloid leukemia (AML) remains challenging. This retrospective single-center study investigates outcomes of AML patients transplanted with active disease who experienced relapse after HCT. We analyzed 67 patients who relapsed after HCT between 2014 and 2024. Patients were classified as having impending molecular relapse (n = 42, defined by persistent or recurrent genetic aberrations and/or a drop in CD34 + donor chimerism < 95 %) or overt hematologic relapse (n = 25). We evaluated overall survival (OS), relapse-free survival (RFS), and responses to relapse treatments. Thirty-seven (88 %) patients with impending relapse had a decrease in CD34<sup>+</sup> donor chimerism; and only 5 (12 %) patients harbored an impending relapse without decrease in CD34<sup>+</sup> donor chimerism. Two-year OS with impending relapse was 45 % (95 % confidence interval [CI], 31–64 %), with 13 of 23 patients (57 %) achieving measurable residual disease (MRD) negative remissions after donor lymphocyte infusions (DLI). RFS was significantly shorter in patients with impending relapse who did not receive DLI (hazard ratio [HR] 3.23, 95 % CI, 1.22–8.33, <em>P</em> = .02), whereas OS did not differ (HR 2.00, 95 % CI, 0.66–5.88; <em>P</em> = 0.22). Patients with overt relapse had poor outcomes with a 1-year survival of 24 % (95 % CI, 12–48 %). Our data underscore the importance of close follow-up after transplantation, especially in high-risk AML. Whenever relapse is imminent, timely immune-based therapy may induce durable MRD-negative remissions and was associated with improved RFS compared to hypomethylating agents without DLI in our cohort.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"160 ","pages":"Article 108153"},"PeriodicalIF":2.2,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145827925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-12DOI: 10.1016/j.leukres.2025.108148
Min Zou, Bolin Wan, Jing Hu
Introduction
Relapsed or refractory acute lymphoblastic leukemia (R/R ALL) remains a major therapeutic challenge with poor long-term survival outcomes. Although checkpoint inhibitors targeting PD-1/PD-L1 have shown efficacy in other hematologic malignancies, their role in ALL has not been fully defined. Combination strategies integrating PD-1/PD-L1 blockade with chemotherapy or CAR-T cells may enhance anti-leukemic responses and overcome immune resistance.
Methods
In this multicenter, open-label Phase II trial, 168 patients with R/R ALL were randomized to receive either FLAG chemotherapy plus nivolumab (Group A), CD19-directed CAR-T cells plus atezolizumab (Group B), or FLAG alone (Control). The primary endpoint was progression-free survival (PFS); secondary outcomes included overall survival (OS), MRD negativity, and safety. Immune profiling assessed biomarkers like PD-L1, TIM-3, CD25 + , and cytokines.
Results
MRD negativity rates were significantly higher in experimental arms compared to control (Group A: 19.5 %; Group B: 27.8 %; Control: 3 %; p < 0.001). Median PFS was 7.7 months in Group A, 11.7 months in Group B, and 4.1 months in the control group (p < 0.001). Median OS was 10.75, 13.5, and 5.65 months, respectively (p < 0.001). Higher baseline PD-L1 expression was independently associated with improved survival (HR 0.90 per 10 % increase; p = 0.002). The addition of checkpoint inhibitors did not significantly increase severe toxicities, and infection rates were lower in experimental groups compared to control. The swimmer plot analysis demonstrated prolonged remission in MRD-negative patients.
Conclusion
Adding PD-1 or PD-L1 blockade to either chemotherapy or CAR-T therapy improved clinical outcomes without excess toxicity in R/R ALL.
{"title":"Efficacy and safety of PD-1/PD-L1 inhibitors in combination with chemotherapy or CAR-T cells for relapsed/refractory acute lymphoblastic leukemia: A multicenter phase ii trial","authors":"Min Zou, Bolin Wan, Jing Hu","doi":"10.1016/j.leukres.2025.108148","DOIUrl":"10.1016/j.leukres.2025.108148","url":null,"abstract":"<div><h3>Introduction</h3><div>Relapsed or refractory acute lymphoblastic leukemia (R/R ALL) remains a major therapeutic challenge with poor long-term survival outcomes. Although checkpoint inhibitors targeting PD-1/PD-L1 have shown efficacy in other hematologic malignancies, their role in ALL has not been fully defined. Combination strategies integrating PD-1/PD-L1 blockade with chemotherapy or CAR-T cells may enhance anti-leukemic responses and overcome immune resistance.</div></div><div><h3>Methods</h3><div>In this multicenter, open-label Phase II trial, 168 patients with R/R ALL were randomized to receive either FLAG chemotherapy plus nivolumab (Group A), CD19-directed CAR-T cells plus atezolizumab (Group B), or FLAG alone (Control). The primary endpoint was progression-free survival (PFS); secondary outcomes included overall survival (OS), MRD negativity, and safety. Immune profiling assessed biomarkers like PD-L1, TIM-3, CD25 + , and cytokines.</div></div><div><h3>Results</h3><div>MRD negativity rates were significantly higher in experimental arms compared to control (Group A: 19.5 %; Group B: 27.8 %; Control: 3 %; p < 0.001). Median PFS was 7.7 months in Group A, 11.7 months in Group B, and 4.1 months in the control group (p < 0.001). Median OS was 10.75, 13.5, and 5.65 months, respectively (p < 0.001). Higher baseline PD-L1 expression was independently associated with improved survival (HR 0.90 per 10 % increase; p = 0.002). The addition of checkpoint inhibitors did not significantly increase severe toxicities, and infection rates were lower in experimental groups compared to control. The swimmer plot analysis demonstrated prolonged remission in MRD-negative patients.</div></div><div><h3>Conclusion</h3><div>Adding PD-1 or PD-L1 blockade to either chemotherapy or CAR-T therapy improved clinical outcomes without excess toxicity in R/R ALL.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"160 ","pages":"Article 108148"},"PeriodicalIF":2.2,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145839660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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