Hematological Oncology最新文献

{"title":"Hypogammaglobulinemia at Diagnosis is Associated With Inferior Survival and Higher Risk of Infections in Diffuse Large B Cell Lymphoma","authors":"Åsa Lindberg,&nbsp;Åsa Johansson,&nbsp;Fredrik Kahn,&nbsp;Göran Jönsson,&nbsp;Mats Jerkeman","doi":"10.1002/hon.70014","DOIUrl":"https://doi.org/10.1002/hon.70014","url":null,"abstract":"<div>\u0000 \u0000 <p>There are some evidences that hypogammaglobulinemia in newly diagnosed diffuse large B cell lymphoma (DLBCL) is a predictor for inferior outcome, but the risk for infection-related admissions specifically related to hypogammaglobulinemia is not known. The aim was to explore if hypogammaglobulinemia in untreated DLBCL in a Swedish cohort was associated with inferior outcome, and to assess the relationship between low immunoglobulin (Ig) levels and infections. Using data from the Swedish Lymphoma Register, we retrospectively identified patients above18 years diagnosed with DLBCL, receiving anthracycline-based curative therapy during 2000–2015 in Southern Sweden with Ig-levels tested at baseline. Data on Ig levels and infections were collected from medical records. Five hundred eighty-five patients were included, median age was 69 years. Hypogammaglobulinemia was detected at baseline in 24%, the most common Ig deficiency was IgG (18%), followed by IgA (10%) and IgM (8%). Hypogammaglobulinemia was associated with inferior overall survival (HR 1.4, 95% CI 1.0–1.8, <i>p</i>-value 0.018), but not when adjusted for International Prognostic Index (IPI). Low levels of Ig were associated with more infections during lymphoma treatment (<i>p</i>-value 0.013), also when adjusted for IPI (<i>p</i>-value &lt; 0.001). Among patients with IgG deficiency, 47% had ≥ 1 infections versus 35% in patients with normal IgG (HR 1.2, <i>p</i> = 0.025). In conclusion, hypogammaglobulinemia was a frequent finding in patients with newly diagnosed DLBCL, with clinical impact in terms of treatment complications and outcome.</p>\u0000 </div>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142763953","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":"Safety and Efficacy of Tinostamustine in a Subpopulation of Patients With Relapsed/Refractory Hodgkin Lymphoma From a Phase I Trial","authors":"Anna Sureda,&nbsp;Antonio Pinto,&nbsp;Hervé Ghesquières,&nbsp;Franck Morschhauser,&nbsp;Olivier Tournilhac,&nbsp;Pim Mutsaers,&nbsp;Josée M. Zijlstra,&nbsp;Rosaria De Filippi,&nbsp;Kasia Hilgier,&nbsp;Nick Manamley,&nbsp;Tomas Janik,&nbsp;Pier Luigi Zinzani","doi":"10.1002/hon.70000","DOIUrl":"https://doi.org/10.1002/hon.70000","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>A significant unmet need remains for patients with Hodgkin lymphoma (HL) who fail to respond to first-line treatment or experience an early relapse. Tinostamustine, a novel alkylating deacetylase inhibitor, inhibits tumor cell growth and slows disease progression in models of hematological malignancies and solid tumors. This was a Phase I, multicenter, open-label, two-stage trial investigating the safety and efficacy of tinostamustine in patients ≥ 18 years with relapsed/refractory (R/R) hematological malignancies, including HL. Stage 1 involved dose-escalation to determine the maximum tolerated dose (MTD) of tinostamustine, optimal infusion time and recommended Phase II dose (RP2D). Stage 2 confirmed the safety and efficacy of the RP2D in expansion cohorts of selected R/R hematological malignancies. Ten patients with heavily pre-treated HL entered dose-escalation, with nine patients experiencing treatment-emergent adverse events (TEAEs) considered to be related to study treatment—primarily hematological toxicities. MTD was 100 mg/m² tinostamustine over 60 min and signals of efficacy were observed for patients with HL. In Stage 2, all 20 patients with HL experienced ≥ 1 TEAE, which were principally hematological or gastrointestinal. There were no tinostamustine-related deaths in either stage of the study. Overall response rate in Stage 2 was 37% (2 complete responses, 5 partial responses; 95% confidence interval [CI]: 16%, 62%) and median progression-free survival 3.8 months (95% CI: 2.2–9.4 months). Tinostamustine is a promising new therapeutic approach for the treatment of patients with R/R classical HL with limited options. This study demonstrates a predictable and manageable safety profile with signals of efficacy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <p><b>Trial Registration:</b> ClinicalTrials.gov identifier: NCT02576496</p>\u0000 </section>\u0000 </div>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70000","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142759828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PET2-Adapted Therapy in Patients With Advanced-Stage Hodgkin Lymphoma Treated With Frontline ABVD: Searching for the Baby in the Bathwater","authors":"Antonio Pinto,&nbsp;Annarosa Cuccaro,&nbsp;Matteo Bonanni,&nbsp;Alberto Fresa,&nbsp;Rosaria De Filippi,&nbsp;Gaetano Corazzelli","doi":"10.1002/hon.70004","DOIUrl":"10.1002/hon.70004","url":null,"abstract":"","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142754978","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":"Molecular Features of Diffuse Large B-Cell Lymphoma Associated With Primary Treatment Resistance","authors":"Allison M. Bock,&nbsp;Kerstin Wenzl,&nbsp;Joseph P. Novak,&nbsp;Matthew E. Stokes,&nbsp;Melissa A. Hopper,&nbsp;Jordan E. Krull,&nbsp;Abigail R. Dropik,&nbsp;Vivek Sarangi,&nbsp;Maria Ortiz,&nbsp;Nicholas Stong,&nbsp;C. Chris Huang,&nbsp;Matthew J. Maurer,&nbsp;Rebecca L. King,&nbsp;Umar Farooq,&nbsp;Yucai Wang,&nbsp;Thomas E. Witzig,&nbsp;Stephen M. Ansell,&nbsp;Thomas M. Habermann,&nbsp;James R. Cerhan,&nbsp;Anita K. Gandhi,&nbsp;Grzegorz Nowakowski,&nbsp;Anne J. Novak","doi":"10.1002/hon.70006","DOIUrl":"10.1002/hon.70006","url":null,"abstract":"<p>Diffuse large B-cell lymphoma (DLBCL) patients that fail to achieve a complete metabolic response with frontline immunochemotherapy have a poor prognosis. Genomic profiling has led to a broader understanding of the molecular drivers in DLBCL, but it is unknown how well current classifiers identify patients that will experience primary treatment resistance (PTR). Using whole exome and RNA sequencing data from newly diagnosed DLBCL patients, we evaluated the genomic landscape of PTR and compared it to that of non-PTR DLBCL. We found a significant increase in the frequency of <i>TP53</i> (34% vs. 15%, <i>p</i> = 0.005) and <i>ARID1A</i> mutations (21% vs. 7%, <i>p</i> = 0.007) in PTR cases, with pathway analysis further demonstrating a downregulation of TP53 and an increase in chromatin modifying pathways. These results suggest that <i>TP53</i> and <i>ARID1A</i> may be key mediators of PTR and important pathways contributing to the poor outcomes. We found that the current molecular classifiers were unable to identify PTR cases at diagnosis. However, our newly identified high-risk signature identified 46% of PTR cases at diagnosis. Overall, these results contribute to our understanding of the genomic landscape of patients with primary treatment resistance.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142754976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic Role of Pretreatment Tumor Burden and Dissemination Features From 2-[18F]FDG PET/CT in Advanced Mantle Cell Lymphoma","authors":"Domenico Albano,&nbsp;Nicola Bianchetti,&nbsp;Anna Talin,&nbsp;Francesco Dondi,&nbsp;Alessandro Re,&nbsp;Alessandra Tucci,&nbsp;Francesco Bertagna","doi":"10.1002/hon.70009","DOIUrl":"10.1002/hon.70009","url":null,"abstract":"<p>Mantle cell lymphoma (MCL) is an aggressive non-Hodgkin lymphoma with poor prognosis. The usefulness of fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (2-[¹⁸F]FDG PET/CT) and its parameters in the evaluation of treatment response and prognosis is not yet clear. The aim of this study was to investigate the prognostic role of tumor burden and tumor dissemination features derived by 2-[¹⁸F]FDG PET/CT in advanced MCL. We retrospectively included 120 patients with advanced MCL who underwent baseline 2- 2-[¹⁸F]FDG PET/CT and end-of-treatment (eot) PET/CT. The baseline-PET images were analyzed visually and semi-quantitatively by measuring the maximum standardized uptake value body weight (SUVbw), lean body mass (SUVlbm), body surface area (SUVbsa), metabolic tumor volume (MTV), total lesion glycolysis (TLG) and dissemination features (Dmax and Dmax-bsa). EotPET/CT was judged according to the Lugano classification. Progression-free survival (PFS) and overall survival (OS) were plotted according to the Kaplan–Meier method. At a median follow-up of 59 months, relapse/progression occurred in 68 patients while death in 38 patients with a median PFS and OS of 27.2 and 57.6 months, respectively. MIPI score, Bulky disease, Ki-67 index, metabolic response, pretreatment MTV and TLG were significantly associated with PFS at univariate analysis, but only metabolic response, MTV and TLG were confirmed to be independent prognostic factors. Considering OS, only dissemination features were demonstrated to be prognostic features. In conclusions, metabolic response and metabolic tumor burden parameters (MTV and TLG) are strongest predictor of PFS, while dissemination features may have a significant role for predicting OS.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142754980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ibrutinib With Bendamustine and Rituximab for Treatment of Patients With Relapsed/Refractory Aggressive B-Cell Lymphoma","authors":"Meirav Kedmi,&nbsp;Elena Ribakovsy,&nbsp;Ohad Benjamini,&nbsp;Ginette Schiby,&nbsp;Iris Barshack,&nbsp;Stephen Raskin,&nbsp;Yael Eshet,&nbsp;Ramit Mehr,&nbsp;Netanel Horowitz,&nbsp;Ronit Gurion,&nbsp;Neta Goldschmidt,&nbsp;Chava Perry,&nbsp;Itai Levi,&nbsp;Ariel Aviv,&nbsp;Katrin Herzog-Tzarfati,&nbsp;Arnon Nagler,&nbsp;Abraham Avigdor","doi":"10.1002/hon.70001","DOIUrl":"https://doi.org/10.1002/hon.70001","url":null,"abstract":"<div>\u0000 \u0000 <p>Therapy for relapsed or refractory (R/R) aggressive B-cell non-Hodgkin lymphoma (aB-NHL) post autologous stem cell transplantation (ASCT) or in elderly patients can be challenging. In this single-center, single-arm, phase II clinical study, we investigated the efficacy of ibrutinib (560 mg once daily) in combination with bendamustine and rituximab (IBR) given for six 28-day cycles in their standard dose, to patients with R/R aB-NHL who were either transplant ineligible in first or second relapse or post-ASCT for second relapse. The primary endpoint was overall response rate (ORR). Fifty-six patients (54% male, median age 69.7 years) were included. ORR was 49.1% among 55 patients treated with ≥ 1 cycle of IBR and 69.4% among 36 patients treated with ≥ 3 cycles. Patients with relapsed disease had significantly higher ORR compared to those with refractory disease (72.3% vs. 37.8%, <i>p</i> = 0.024). Median overall survival (OS) was 11.6 months (95% CI, 7.1–22.3) and median progression-free survival was 5.3 months (95% CI, 2.5–7.4). Patients with complete and partial responses had significantly longer median OS compared to those with stable and progressive disease (28.1 vs. 5.2 months, <i>p</i> &lt; 0.0001). Adverse events included thrombocytopenia (19.6%), anemia (16.1%), neutropenia (7.1%), fatigue (35.7%), diarrhea (28.6%) and nausea (28.6%). At the first efficacy evaluation 8 patients were referred to transplantation, and 3 more were referred during follow-up. These data indicate that the IBR regimen is a safe and effective treatment option that can also be used for bridging to transplantation in patients with R/R aB-NHL.<b>Trial Registration:</b> ClinicalTrials.gov: NCT02747732</p>\u0000 </div>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"42 6","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142685360","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":"Liposomal Doxorubicin, Vinblastine and Dacarbazine Plus Consolidation Radiotherapy of Residual Nodal Masses for Frontline Treatment in Older Adults With Advanced Stage Classic Hodgkin Lymphoma: Improved Outcome in a Multi-Center Real-Life Study","authors":"M. Picardi,&nbsp;A. Vincenzi,&nbsp;C. Giordano,&nbsp;L. De Fazio,&nbsp;N. Pugliese,&nbsp;A. Scarpa,&nbsp;E. Vigliar,&nbsp;G. Troncone,&nbsp;D. Russo,&nbsp;M. Mascolo,&nbsp;G. Esposito,&nbsp;M. Prastaro,&nbsp;C. Santoro,&nbsp;R. Esposito,&nbsp;C. G. Tocchetti,&nbsp;C. Mainolfi,&nbsp;R. Fonti,&nbsp;S. Del Vecchio,&nbsp;M. Carchia,&nbsp;C. Quagliano,&nbsp;A. Salemme,&nbsp;V. Damiano,&nbsp;R. Bianco,&nbsp;F. Trastulli,&nbsp;F. Ronconi,&nbsp;M. Annunziata,&nbsp;F. Pane","doi":"10.1002/hon.70003","DOIUrl":"10.1002/hon.70003","url":null,"abstract":"<p>In elderly patients with high-risk classic Hodgkin lymphoma (c-HL), we evaluated the impact of a new modality treatment without bleomycin, that is, liposomal doxorubicin (NPLD)-based regimen plus consolidation radiotherapy of residual nodal masses (RNMs), on overall survival (OS) and progression free survival (PFS). In this retrospective study (2013–2023) conducted in tertiary hospitals in the bay of Naples (Italy), 50 older adults (median age, 69 years; range, 60–89) with advanced stage c-HL received frontline treatment with MVD ± irradiation. MVD consisted of 25 mg/m² of NPLD along with standard Vinblastine and Dacarbazine for a total of 6 cycles (twelve iv administrations, every 2 weeks) followed by radiation of RNMs with size ≥ 2.5 cm at computed tomography. Patients underwent MVD with a median dose intensity of 92%. At 2-deoxy-2[F-18] fluoro-D-glucose positron emission tomography (FDG-PET), 90% of patients (45/50 patients; one failed to perform final FDG-PET due to early death) reached complete responses. Altogether, 17 patients (34%) received consolidation radiotherapy of RNMs with Deauville score ≥ 3. At 5-year median follow-up, the OS and PFS of the entire population were 87.5% (95% confidence interval [CI], 78.7–97.4) and 81.6% (95% CI, 71.4–93.2), respectively. Eleven patients (22%) experienced grade ≥ 3 adverse events, and 4 of them required hospitalization. Our data suggest that in older adults with high-risk c-HL NPLD-driven strategy (without bleomycin) plus consolidation radiotherapy (if needed) may be a promising up-front option, to test in phase II clinical trials for improving survival incidence.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"42 6","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CAT rs1001179 Single Nucleotide Polymorphism Identifies an Aggressive Clinical Behavior in Chronic Lymphocytic Leukemia","authors":"Marilisa Galasso,&nbsp;Vittoria Salaorni,&nbsp;Riccardo Moia,&nbsp;Valentina Mozzo,&nbsp;Ester Lovato,&nbsp;Chiara Cosentino,&nbsp;Omar Perbellini,&nbsp;Simona Gambino,&nbsp;Ornella Lovato,&nbsp;Maria Elena Carazzolo,&nbsp;Isacco Ferrarini,&nbsp;Francesca M. Quaglia,&nbsp;Massimo Donadelli,&nbsp;Maria G. Romanelli,&nbsp;Carlo Visco,&nbsp;Mauro Krampera,&nbsp;Gianluca Gaidano,&nbsp;Maria T. Scupoli","doi":"10.1002/hon.70002","DOIUrl":"10.1002/hon.70002","url":null,"abstract":"<p>Chronic lymphocytic leukemia (CLL) is characterized by an extremely variable clinical course. Although several parameters have been shown to be associated with clinical outcomes in patients with CLL, there remains substantial intragroup clinical heterogeneity in otherwise molecularly and staging homogeneous CLL subgroups. We have recently shown that high catalase (CAT) expression identifies patients with an aggressive clinical course and that higher <i>CAT</i> expression is associated with the presence of the rs1001179 single nucleotide polymorphism (SNP) T allele in the <i>CAT</i> promoter. Herein, we genotyped CLL patients for <i>CAT</i> rs1001179 SNP in an exploratory study (<i>n</i> = 235) and in a sequential independent validation study (<i>n</i> = 531). Time-to-event modeling analyses for time-to-first-treatment (TTFT) from the two patients' cohorts showed that TT genotype was associated with a shorter TTFT, independently of other currently used prognostic parameters in CLL. Moreover, the TT genotype identifies CLL patients with a faster clinical progression even within subgroups of patients with low-risk biological and clinical hallmarks. In conclusion, our data show that the TT genotype identifies CLL patients with a shorter TTFT, pointing to this SNP as a possible prognostic factor, which can improve patients' risk stratification leading to better patient management and personalized therapeutic choices.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"42 6","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142618773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Isocitrate dehydrogenase 2 mutation promotes cytarabine resistance in acute myeloid leukemia by Warburg effect","authors":"Jinrong Yang,&nbsp;Zixu Wang,&nbsp;Kun Wu,&nbsp;Bo Nie,&nbsp;Liyin Li,&nbsp;Jingyan Ruan,&nbsp;Qiang Zhou,&nbsp;Yun Zeng,&nbsp;Mingxia Shi","doi":"10.1002/hon.3316","DOIUrl":"10.1002/hon.3316","url":null,"abstract":"<p>Mutation of isocitrate dehydrogenase 2 (IDH2) is a key factor in promoting cytarabine (Ara-C) resistance in acute myeloid leukemia (AML), however the underly mechanism remains unclear. Acute myeloid leukemia cells, were cultured with either IDH2 knockdown (KD-IDH2) or overexpression (OE-IDH2) to elucidate the role of IDH2 in these leukemic cell lines. Additionally, mutant cell lines were engineered to replicate clinically relevant IDH2 mutations. To investigate cellular responses, the glycolytic inhibitor 2-deoxy-D-glucose (2-DG) was administered to the cells. Cell proliferation was quantified using a Cell Counting Kit-8 (CCK-8), while apoptosis was evaluated through propidium iodide staining followed by flow cytometry. Glycolytic metabolism levels were measured using a specific reagent kit, and Western blotting was employed to determine the expression levels of glycolysis-related proteins. Transcriptome sequencing was conducted to elucidate the mechanisms by which IDH2 mutations influence glycolysis. Furthermore, both in vitro cell experiments and in vivo subcutaneous transplantation tumor models in nude mice were utilized to validate these mechanisms. OE-IDH2 in AML cells, enhances resistance to the Ara-C, promotes cell proliferation and glycolysis, and inhibits apoptosis. KD-IDH2 exhibits opposite effects. Both IDH2 mutations and OE-IDH2 produce similar effects on these cellular processes. The increase in glycolysis levels following IDH2 mutation may contribute to the reduced efficacy of Enasidenib in inhibiting the proliferation of IDH-mutant AML cells. Transcriptome sequencing results indicate an enrichment of the PI3K/Akt signaling pathway in IDH2-mutant AML cells. BEZ235 significantly inhibits the expression of phosphorylated PI3K (p-PI3K), phosphorylated Akt (p-Akt), mTOR, glycolytic metabolism, and Ara-C resistance both in vitro and in vivo. Overexpression and mutation of IDH2 coordinate with the Warburg effect through the PI3K/Akt/mTOR pathway to promote Ara-C resistance in AML.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"42 6","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.3316","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142618774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Allogeneic transplantation for adult T-cell leukemia/lymphoma in adolescent and young adults and young patients: A nationwide retrospective study by the ATL working group of the Japan society for transplantation and cellular therapy","authors":"Hidehiro Itonaga,&nbsp;Takuya Fukushima,&nbsp;Koji Kato,&nbsp;Nobuaki Nakano,&nbsp;Takeharu Kato,&nbsp;Takashi Tanaka,&nbsp;Tetsuya Eto,&nbsp;Yasuo Mori,&nbsp;Toshiro Kawakita,&nbsp;Naoyuki Uchida,&nbsp;Machiko Fujioka,&nbsp;Hirohisa Nakamae,&nbsp;Masao Ogata,&nbsp;Satoko Morishima,&nbsp;Takahiro Fukuda,&nbsp;Yoshinobu Kanda,&nbsp;Yoshiko Atsuta,&nbsp;Shigeo Fuji,&nbsp;Makoto Yoshimitsu","doi":"10.1002/hon.3315","DOIUrl":"10.1002/hon.3315","url":null,"abstract":"<p>Allogeneic hematopoietic stem cell transplantation (allo-HSCT) provides durable remission for patients with adult T-cell leukemia/lymphoma (ATL); however, few studies have focused on post-transplant outcomes in ATL patients ≤49 years. To clarify prognostic factors in ATL among patients &lt;40 years (adolescents and young adult [AYA]; <i>n</i> = 73) and 40–49 years (Young; <i>n</i> = 330), we conducted a nationwide retrospective study. Estimated 3-year overall survival (OS) rates were 61.8% and 43.1% in AYA and Young patients, respectively (<i>p</i> = 0.005). In the multivariate analysis, Young patients showed worse OS (Hazard ratio (HR) [95% confidential interval] 1.62 [1.10–2.39], <i>p</i> = 0.015), chronic graft-versus-host disease (GVHD)-free and relapse-free survival (CRFS) (HR 1.54 [1.10–2.14], <i>p</i> = 0.011), and GVHD-free and relapse-free survival (GRFS) (HR 1.40 [1.04–1.88], <i>p</i> = 0.026) than AYA patients. No significant differences were observed in OS, CRFS, or GRFS between the myeloablative conditioning (MAC) and reduced-intensity conditioning (RIC) regimens; however, non-relapse mortality was significantly lower in patients with the RIC regimen than those with the MAC regimen (HR 0.46 [0.24–0.86], <i>p</i> = 0.015). In summary, OS was worse in Young patients than in AYA patients in the allo-HSCT setting for ATL. Furthermore, the RIC regimen has potential as an alternative treatment option for ATL patients ≤49 years.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"42 6","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375294","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}