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 : 2025-12-17DOI: 10.1016/j.leukres.2025.108147
Vincent Lok, Katie Moffitt, Dahniel Sastow, Georgio Medawar, Su Bin Hahn, Preston Perez, Abigail Demers, Alexander Coltoff, Douglas Tremblay, Joshua Zeidner, David M. Swoboda
{"title":"Clinical utility of interim bone marrow biopsies in FLT3 mutant acute myeloid leukemia","authors":"Vincent Lok, Katie Moffitt, Dahniel Sastow, Georgio Medawar, Su Bin Hahn, Preston Perez, Abigail Demers, Alexander Coltoff, Douglas Tremblay, Joshua Zeidner, David M. Swoboda","doi":"10.1016/j.leukres.2025.108147","DOIUrl":"10.1016/j.leukres.2025.108147","url":null,"abstract":"","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"161 ","pages":"Article 108147"},"PeriodicalIF":2.2,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146024969","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}
Pub Date : 2025-12-04DOI: 10.1016/j.leukres.2025.108146
Fujiko Tsukahara , Kenjiro Kaji, Yoshiro Maru
While tyrosine kinase inhibitors (TKIs) can effectively counteract BCR::ABL1 activity, resistance by BCR::ABL1 overexpression is a significant challenge in combating chronic myeloid leukemia, making down-regulation of BCR::ABL1 a promising anti-cancer strategy. We previously reported that the ubiquitin ligases c-Cbl and CHIP mediate BCR::ABL1 protein degradation. Bag1, a nucleotide exchange factor for Hsc70, senses immature structures of Hsp90-unchaperoned BCR::ABL1 protein and stimulates CHIP-induced BCR::ABL1 degradation. Peptidyl-prolyl cis/trans isomerases (PPIases) have been shown to regulate protein conformations for stability and degradation, while nothing is known about the PPIases for BCR::ABL1. Here we identified the parvulin-type Pin1 as a new regulatory component of BCR::ABL1 degradation system. Among several PPIases tested, we found that Pin1 specifically binds to BCR::ABL1 protein for degradation. Using a series of BCR::ABL1 mutants, we identified the SH2-binding domain of BCR portion as the Pin1 binding region. The Pin1 WW domain appears to associate with the one or more S/T-Pro motif(s) in the SH2 binding region of BCR::ABL1. Pin1 stimulates not only Hsp90 inhibitor- but also PP2A-induced protein degradation. We also found that Pin1 effectively inhibited TKI-induced BCR::ABL1 stabilization. Pin1 may convert the mature form BCR::ABL1 to an immature form for Bag1 recognition leading to CHIP-mediated ubiquitination and degradation. These findings may lead to provide a molecular basis for the development of new Pin1 related therapeutic strategies against TKI resistance.
{"title":"Identification and characterization of peptidyl-prolyl isomerase Pin1 as a new regulatory component of BCR::ABL1 degradation","authors":"Fujiko Tsukahara , Kenjiro Kaji, Yoshiro Maru","doi":"10.1016/j.leukres.2025.108146","DOIUrl":"10.1016/j.leukres.2025.108146","url":null,"abstract":"<div><div>While tyrosine kinase inhibitors (TKIs) can effectively counteract BCR::ABL1 activity, resistance by BCR::ABL1 overexpression is a significant challenge in combating chronic myeloid leukemia, making down-regulation of BCR::ABL1 a promising anti-cancer strategy. We previously reported that the ubiquitin ligases c-Cbl and CHIP mediate BCR::ABL1 protein degradation. Bag1, a nucleotide exchange factor for Hsc70, senses immature structures of Hsp90-unchaperoned BCR::ABL1 protein and stimulates CHIP-induced BCR::ABL1 degradation. Peptidyl-prolyl cis/trans isomerases (PPIases) have been shown to regulate protein conformations for stability and degradation, while nothing is known about the PPIases for BCR::ABL1. Here we identified the parvulin-type Pin1 as a new regulatory component of BCR::ABL1 degradation system. Among several PPIases tested, we found that Pin1 specifically binds to BCR::ABL1 protein for degradation. Using a series of BCR::ABL1 mutants, we identified the SH2-binding domain of BCR portion as the Pin1 binding region. The Pin1 WW domain appears to associate with the one or more S/T-Pro motif(s) in the SH2 binding region of BCR::ABL1. Pin1 stimulates not only Hsp90 inhibitor- but also PP2A-induced protein degradation. We also found that Pin1 effectively inhibited TKI-induced BCR::ABL1 stabilization. Pin1 may convert the mature form BCR::ABL1 to an immature form for Bag1 recognition leading to CHIP-mediated ubiquitination and degradation. These findings may lead to provide a molecular basis for the development of new Pin1 related therapeutic strategies against TKI resistance.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"160 ","pages":"Article 108146"},"PeriodicalIF":2.2,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145724317","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}
We compared outcomes of patients ≥ 70 years old undergoing allogeneic stem cell transplantation (alloSCT) with graft-vs-host disease (GvHD) prophylaxis regimens either including post-transplant cyclophosphamide (PTCy) or without cyclophosphamide (non-Cy). The primary endpoint was GvHD-free, relapse-free survival (GRFS) at one and five years; secondary endpoints included clinically significant acute (grade III-IV) and chronic (extensive) GvHD, relapse, overall survival (OS), and non-relapse mortality (NRM). Among 61 patients, 41 received PTCy and 20 received non-Cy prophylaxis. Unrelated donors accounted for 80 % of allografts; all non-Cy patients had 10/10 HLA matches, while PTCy patients had 64 % matched, 29 % haploidentical, and 7 % mismatched unrelated donors. Acute GvHD occurred in 5 % of PTCy vs 15 % of non-Cy patients (p = ns). One-year chronic GvHD incidence was lower with PTCy (12 % vs 30 %, p = 0.03). One-year GRFS was similar (34 % PTCy, 35 % non-Cy; p = ns). At five years, OS was 20 % vs 30 % and GRFS 21 % vs 15 % for PTCy and non-Cy, respectively (p = ns). We observed similar outcomes among patients receiving GvHD prophylaxis with PTCy compared to non-Cy. Importantly, non-Cy patients had HLA-matched donors, whereas mismatched donors were possible for the PTCy group. In this way, PTCy seems to have equalized outcomes for fully matched and mismatched alloSCT by yielding similar one and five-year GRFS. We also found no significant difference in relapse rate, NRM, OS, and five-year GRFS between patients aged 70–74 and ages 75 + , showing that numerical age should not be a contraindication to alloSCT.
{"title":"Outcomes of adults older than 70 years of age undergoing allogeneic stem cell transplantation","authors":"Ishan Bhatia , Shyam Patel , Laurie Pearson , Kayal Parthiban , Sakiko Suzuki , Poorva Bindal , Andrew Gillis-Smith , Muthalagu Ramanathan , Jonathan Gerber , Rajneesh Nath , Jan Cerny","doi":"10.1016/j.leukres.2025.108145","DOIUrl":"10.1016/j.leukres.2025.108145","url":null,"abstract":"<div><div>We compared outcomes of patients ≥ 70 years old undergoing allogeneic stem cell transplantation (alloSCT) with graft-vs-host disease (GvHD) prophylaxis regimens either including post-transplant cyclophosphamide (PTCy) or without cyclophosphamide (non-Cy). The primary endpoint was GvHD-free, relapse-free survival (GRFS) at one and five years; secondary endpoints included clinically significant acute (grade III-IV) and chronic (extensive) GvHD, relapse, overall survival (OS), and non-relapse mortality (NRM). Among 61 patients, 41 received PTCy and 20 received non-Cy prophylaxis. Unrelated donors accounted for 80 % of allografts; all non-Cy patients had 10/10 HLA matches, while PTCy patients had 64 % matched, 29 % haploidentical, and 7 % mismatched unrelated donors. Acute GvHD occurred in 5 % of PTCy vs 15 % of non-Cy patients (p = ns). One-year chronic GvHD incidence was lower with PTCy (12 % vs 30 %, p = 0.03). One-year GRFS was similar (34 % PTCy, 35 % non-Cy; p = ns). At five years, OS was 20 % vs 30 % and GRFS 21 % vs 15 % for PTCy and non-Cy, respectively (p = ns). We observed similar outcomes among patients receiving GvHD prophylaxis with PTCy compared to non-Cy. Importantly, non-Cy patients had HLA-matched donors, whereas mismatched donors were possible for the PTCy group. In this way, PTCy seems to have equalized outcomes for fully matched and mismatched alloSCT by yielding similar one and five-year GRFS. We also found no significant difference in relapse rate, NRM, OS, and five-year GRFS between patients aged 70–74 and ages 75 + , showing that numerical age should not be a contraindication to alloSCT.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"160 ","pages":"Article 108145"},"PeriodicalIF":2.2,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145681837","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 : 2025-11-28DOI: 10.1016/j.leukres.2025.108144
Cameron J. Hunter , Andrew Chou , Heidi Roeder , William Eighmy , Jan Philipp Bewersdorf , Lourdes Mendez , Maximilian Stahl , Nikolai A. Podoltsev , Amer M. Zeidan , Rory M. Shallis
Voriconazole has been a standard antifungal prophylactic (AFP) agent for patients with acute myeloid leukemia (AML) during neutropenia. However, its use is complicated by side-effects including transaminase elevations, visual disturbances, and significant drug-drug interactions (DDIs). Isavuconazole is an AFP agent with a more attractive side-effect profile. In a retrospective analysis we compared rates of complications necessitating AFP withdrawal between patients with AML who initially started on isavuconazole (n = 63) or voriconazole (n = 215), and of invasive fungal infection (IFI) and median overall survival (OS) between patients who used only isavuconazole (n = 41) or voriconazole (n = 90). Voriconazole was associated with higher rates of AFP discontinuation due to transaminase elevations (p = 0.019), visual disturbances (p = 0.002), or DDIs (p = 0.002), while isavuconazole was more frequently discontinued due to coverage denial/high cost (p < 0.0001). Rates/classification of IFI, breakthrough IFI (bIFI) and IFI-free survival (IFI-FS) were comparable between azoles in both analyses. Isavuconazole is an effective AFP agent with a superior side-effect profile and should thus be considered as a promising AFP option for patients with AML.
{"title":"Isavuconazole provides effective and tolerable antifungal prophylaxis for patients with acute myeloid leukemia","authors":"Cameron J. Hunter , Andrew Chou , Heidi Roeder , William Eighmy , Jan Philipp Bewersdorf , Lourdes Mendez , Maximilian Stahl , Nikolai A. Podoltsev , Amer M. Zeidan , Rory M. Shallis","doi":"10.1016/j.leukres.2025.108144","DOIUrl":"10.1016/j.leukres.2025.108144","url":null,"abstract":"<div><div>Voriconazole has been a standard antifungal prophylactic (AFP) agent for patients with acute myeloid leukemia (AML) during neutropenia. However, its use is complicated by side-effects including transaminase elevations, visual disturbances, and significant drug-drug interactions (DDIs). Isavuconazole is an AFP agent with a more attractive side-effect profile. In a retrospective analysis we compared rates of complications necessitating AFP withdrawal between patients with AML who initially started on isavuconazole (n = 63) or voriconazole (n = 215), and of invasive fungal infection (IFI) and median overall survival (OS) between patients who used only isavuconazole (n = 41) or voriconazole (n = 90). Voriconazole was associated with higher rates of AFP discontinuation due to transaminase elevations (p = 0.019), visual disturbances (p = 0.002), or DDIs (p = 0.002), while isavuconazole was more frequently discontinued due to coverage denial/high cost (p < 0.0001). Rates/classification of IFI, breakthrough IFI (bIFI) and IFI-free survival (IFI-FS) were comparable between azoles in both analyses. Isavuconazole is an effective AFP agent with a superior side-effect profile and should thus be considered as a promising AFP option for patients with AML.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"160 ","pages":"Article 108144"},"PeriodicalIF":2.2,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145715027","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 : 2025-11-25DOI: 10.1016/j.leukres.2025.108142
Pragya Jain , Iqra Qazi , Jacob Thompson , Nency Ganatra , Shivam Patel , Pakeeza Saif , Junaid Anwar
Neutropenic enterocolitis (NE) is an uncommon but serious complication in patients with acute myeloid leukemia (AML), often arising during periods of myelosuppression. Although recognized clinically, its broader impact on hospitalization outcomes and healthcare utilization in AML is poorly defined. To evaluate the association between NE and key inpatient outcomes, including in-hospital mortality, length of stay (LOS), and total hospital charges among patients with AML, this retrospective cross-sectional analysis was performed using the Nationwide Inpatient Sample (NIS) from 2018 to 2022. Multivariable models were fitted using survey-weighted logistic regression for mortality and Poisson regression with a log link for LOS and charges, adjusting for demographic and clinical covariates to calculate adjusted odds ratios (aORs) and adjusted incidence rate ratios (aIRRs), with corresponding 95 % confidence intervals (CIs). Among an estimated 344,545 AML hospitalizations, 3865 involved NE, which were associated with significantly longer hospitalizations and higher costs. In adjusted models, NE increased LOS by nearly 50 % (aIRR: 1.47, 95 % CI: 1.41–1.54) and total charges by over 40 % (aIRR: 1.44, 95 % CI: 1.35–1.53), with both associations being highly significant (p < 0.0001). In contrast, NE was not independently associated with in-hospital mortality (aOR: 0.89, 95 % CI: 0.75–1.06; p = 0.20). This study's findings indicate that, though NE was not a predictor of mortality, it is a strong driver of healthcare utilization in patients hospitalized with AML. These findings underscore NE’s importance as a complication with major clinical and economic implications, highlighting the need for strategies to improve recognition and management in this vulnerable population.
{"title":"Neutropenic enterocolitis in acute myeloid leukemia: A nationwide inpatient cross-sectional study","authors":"Pragya Jain , Iqra Qazi , Jacob Thompson , Nency Ganatra , Shivam Patel , Pakeeza Saif , Junaid Anwar","doi":"10.1016/j.leukres.2025.108142","DOIUrl":"10.1016/j.leukres.2025.108142","url":null,"abstract":"<div><div>Neutropenic enterocolitis (NE) is an uncommon but serious complication in patients with acute myeloid leukemia (AML), often arising during periods of myelosuppression. Although recognized clinically, its broader impact on hospitalization outcomes and healthcare utilization in AML is poorly defined. To evaluate the association between NE and key inpatient outcomes, including in-hospital mortality, length of stay (LOS), and total hospital charges among patients with AML, this retrospective cross-sectional analysis was performed using the Nationwide Inpatient Sample (NIS) from 2018 to 2022. Multivariable models were fitted using survey-weighted logistic regression for mortality and Poisson regression with a log link for LOS and charges, adjusting for demographic and clinical covariates to calculate adjusted odds ratios (aORs) and adjusted incidence rate ratios (aIRRs), with corresponding 95 % confidence intervals (CIs). Among an estimated 344,545 AML hospitalizations, 3865 involved NE, which were associated with significantly longer hospitalizations and higher costs. In adjusted models, NE increased LOS by nearly 50 % (aIRR: 1.47, 95 % CI: 1.41–1.54) and total charges by over 40 % (aIRR: 1.44, 95 % CI: 1.35–1.53), with both associations being highly significant (p < 0.0001). In contrast, NE was not independently associated with in-hospital mortality (aOR: 0.89, 95 % CI: 0.75–1.06; p = 0.20). This study's findings indicate that, though NE was not a predictor of mortality, it is a strong driver of healthcare utilization in patients hospitalized with AML. These findings underscore NE’s importance as a complication with major clinical and economic implications, highlighting the need for strategies to improve recognition and management in this vulnerable population.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"160 ","pages":"Article 108142"},"PeriodicalIF":2.2,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145621991","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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