Leukemia research最新文献

{"title":"Identification and characterization of peptidyl-prolyl isomerase Pin1 as a new regulatory component of BCR::ABL1 degradation","authors":"Fujiko Tsukahara ,&nbsp;Kenjiro Kaji,&nbsp;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":"2026-01-01","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}

{"title":"Outcomes of adults older than 70 years of age undergoing allogeneic stem cell transplantation","authors":"Ishan Bhatia ,&nbsp;Shyam Patel ,&nbsp;Laurie Pearson ,&nbsp;Kayal Parthiban ,&nbsp;Sakiko Suzuki ,&nbsp;Poorva Bindal ,&nbsp;Andrew Gillis-Smith ,&nbsp;Muthalagu Ramanathan ,&nbsp;Jonathan Gerber ,&nbsp;Rajneesh Nath ,&nbsp;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":"2026-01-01","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}

{"title":"Genomic profiles of myelodysplastic neoplasm with bone marrow eosinophilia or basophilia: Inflammatory drivers and DNA damage response","authors":"Yujin Jung ,&nbsp;Su Sung Kim ,&nbsp;Sooyong Park ,&nbsp;Dajeong Jeong ,&nbsp;Ja-Yoon Gu ,&nbsp;Jee-Soo Lee ,&nbsp;Seon Young Kim ,&nbsp;Yoon Hwan Chang ,&nbsp;Moon-Woo Seong ,&nbsp;Hongseok Yun ,&nbsp;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}

{"title":"Relapse after allogeneic hematopoietic stem cell transplantation in patients with active acute myeloid leukemia","authors":"Julian Ronnacker ,&nbsp;Marc-Andre Urbahn ,&nbsp;Christian Reicherts ,&nbsp;Lina Kolloch ,&nbsp;Philipp Berning ,&nbsp;Andrew F. Berdel ,&nbsp;Simon Call ,&nbsp;Matthias Floeth ,&nbsp;Julia Marx ,&nbsp;Eva Eßeling ,&nbsp;Jan-Henrik Mikesch ,&nbsp;Christoph Schliemann ,&nbsp;Hans Theodor Eich ,&nbsp;Georg Lenz ,&nbsp;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 &lt; 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, <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":"2026-01-01","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}

{"title":"Neutropenic enterocolitis in acute myeloid leukemia: A nationwide inpatient cross-sectional study","authors":"Pragya Jain ,&nbsp;Iqra Qazi ,&nbsp;Jacob Thompson ,&nbsp;Nency Ganatra ,&nbsp;Shivam Patel ,&nbsp;Pakeeza Saif ,&nbsp;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 &lt; 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":"2026-01-01","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}

{"title":"Outcomes of two distinct T-cell depletion strategies in haploidentical vs unrelated donor pediatric HSCT: A single-center retrospective analysis","authors":"Luisa Sisinni ,&nbsp;Odelaisy León-Triana ,&nbsp;Mikel Fernandez Artazcoz ,&nbsp;Mauro Guariento ,&nbsp;Iñigo Figueroa Real de Asua ,&nbsp;Yasmina Mozo del Castillo ,&nbsp;Paula Lazaro del Campo ,&nbsp;David Bueno Sanchez ,&nbsp;Carmen Mestre Durán ,&nbsp;Jordi Minguillón Pedreño ,&nbsp;Mercedes Gasior Kabat ,&nbsp;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":"2026-01-01","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}

{"title":"Genomic profiling reveals molecular heterogeneity in patients with Richter transformation (RT) and chronic lymphocytic leukemia (CLL)","authors":"Shulan Tian ,&nbsp;Hanyin Wang ,&nbsp;Sameer A. Parikh ,&nbsp;Yuanhang Liu ,&nbsp;Helen Jin-Lee ,&nbsp;Erik Jessen ,&nbsp;Eric W. Klee ,&nbsp;Yucai Wang ,&nbsp;Fan Leng ,&nbsp;Min Shi ,&nbsp;Cinthya Zepeda-Mendoza ,&nbsp;Rong He ,&nbsp;Saad J. Kenderian ,&nbsp;Linda B. Baughn ,&nbsp;Daniel L. Van Dyke ,&nbsp;Paul J. Hampel ,&nbsp;Neil E. Kay ,&nbsp;Esteban Braggio ,&nbsp;Susan L. Slager ,&nbsp;Huihuang Yan ,&nbsp;Wei Ding","doi":"10.1016/j.leukres.2025.108133","DOIUrl":"10.1016/j.leukres.2025.108133","url":null,"abstract":"<div><div>Richter transformation (RT) represents the development of an aggressive lymphoma in chronic lymphocytic leukemia (CLL). Patients with RT and relapsed CLL have poor outcomes. Yet, the molecular differences between the two entities have not been fully explored. In this pilot study, we conducted RNA-seq and targeted panel sequencing of nodal tissues from 12 patients, including seven with RT and five with CLL. Analysis of RNA-seq data revealed two major clusters, with five RT in cluster C1 and the remaining two RT and all five CLL in C2. Within C2, one of the CLL ultimately developed RT; it showed more similarity to the two RT than to the other CLL in expression profile, suggesting the presence of expression signature for RT prior to the clinical diagnosis. In addition, differentially expressed genes, the majority of which showed higher expression in C1 relative to C2, were enriched in pathways known to be important for CLL pathogenesis or transformation. Deconvolution of the bulk RNA-seq data revealed major differences in cellular composition between the two clusters, notably tumor B cells, macrophages M1, and CD8 + T cells. Furthermore, by targeted sequencing, we identified 51 genes that carried recurrent copy number alterations (CNAs) preferentially occurring in either cluster. Over 80 % of these CNAs occurred in C2, mainly gains of 17q12q25 in CLL. Patients in C1 had shorter overall survival (median 11 months) compared to those in C2 (median 36 months). Together, our findings highlight noticeable differences in transcriptomic and genomic alterations between CLL versus RT.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"160 ","pages":"Article 108133"},"PeriodicalIF":2.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145537567","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}

{"title":"Isavuconazole provides effective and tolerable antifungal prophylaxis for patients with acute myeloid leukemia","authors":"Cameron J. Hunter ,&nbsp;Andrew Chou ,&nbsp;Heidi Roeder ,&nbsp;William Eighmy ,&nbsp;Jan Philipp Bewersdorf ,&nbsp;Lourdes Mendez ,&nbsp;Maximilian Stahl ,&nbsp;Nikolai A. Podoltsev ,&nbsp;Amer M. Zeidan ,&nbsp;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 &lt; 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":"2026-01-01","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}

{"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,&nbsp;Bolin Wan,&nbsp;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 &lt; 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 &lt; 0.001). Median OS was 10.75, 13.5, and 5.65 months, respectively (p &lt; 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":"2026-01-01","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}

{"title":"Interlaboratory cross validation of acute myeloid leukemia fusion genes and mutational targets detected by PCR: Performance of PETHEMA central laboratories","authors":"Margarida Coucelo ,&nbsp;Claudia Sargas ,&nbsp;Rosa Ayala ,&nbsp;María J. Larráyoz ,&nbsp;María Carmen Chillón ,&nbsp;Elena Soria ,&nbsp;Cristina Bilbao ,&nbsp;Esther Prados de la Torre ,&nbsp;Maria Luis Amorim ,&nbsp;Alberto Mirales ,&nbsp;Antonia Cionfrini ,&nbsp;Ana T. Simões ,&nbsp;Ana C. Oliveira ,&nbsp;Rebeca Rodríguez-Veiga ,&nbsp;Pilar Lloret-Madrid ,&nbsp;Yolanda Mendizábal ,&nbsp;Carmen Botella ,&nbsp;Teresa Bernal ,&nbsp;Juan Bergua ,&nbsp;Lorenzo Algarra ,&nbsp;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":"2026-01-01","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}