American Journal of Hematology最新文献

{"title":"Endothelial Activation and Stress Index Serves as a Predictor for Survival in Lymphoma-Associated Hemophagocytic Lymphohistiocytosis: A Retrospective Multicenter Cohort Study of Jiangsu Cooperative Lymphoma Group.","authors":"Yanping Liu,Yimin Ren,Ling Gao,Shanza Ahmed,Xuzhang Lu,Bingzong Li,Chunling Wang,Liang Yu,Miao Sun,Yun Zhuang,Yuqing Miao,Haiwen Ni,Xiaoyan Xie,Xiaofeng Shi,Jingyan Xu,Yunping Zhang,Min Zhao,Min Xu,Wanchuan Zhuang,Weiying Gu,Guoqiang Lin,Haiying Hua,Jianfeng Zhu,Maozhong Xu,Tao Jia,Ping Liu,Lijia Zhai,Tongtong Zhang,Huirong Shan,Qiudan Shen,Lei Fan,Jianyong Li,Wenyu Shi,Yi Miao","doi":"10.1002/ajh.70063","DOIUrl":"https://doi.org/10.1002/ajh.70063","url":null,"abstract":"Lymphoma-associated hemophagocytic lymphohistiocytosis (LA-HLH) is a life-threatening hyperinflammatory syndrome, and hierarchical management based on a prognostic model is important. The endothelial activation and stress index (EASIX) score has demonstrated prognostic utility in recipients of allogeneic stem cell transplantation and chimeric antigen receptor (CAR) T-cell therapy. However, its role in LA-HLH remains unestablished. We conducted a multicenter retrospective analysis of patients with LA-HLH from 28 medical centers to explore the prognostic impacts of EASIX in LA-HLH. EASIX was calculated using baseline lactate dehydrogenase, serum creatinine, and platelet counts. A total of 490 patients with LA-HLH were included and stratified by EASIX quartiles (Q1-Q4). Patients with a higher EASIX score had significantly inferior 2-month survival and overall survival, according to the Kaplan-Meier analysis (log-rank p < 0.001). In multivariable analyses, after adjustment for age, gender, lymphoma type, splenomegaly, bone marrow infiltration, lymphoma status (treatment-naïve versus relapsed/refractory), hemoglobin, absolute neutrophil count, serum ferritin levels, and aspartate aminotransferase, the highest EASIX quartile (Q4) exhibited a 7.01-fold risk of death compared to the lowest quartile (Q1) (Hazard ratio [HR] = 7.01, 95% confidence interval [CI]: 3.98-12.36; p < 0.001). Additionally, the restricted cubic splines (RCS) analysis illustrated an increase in the risk of mortality with an increasing EASIX score. Our findings support EASIX being a robust, universally accessible prognostic marker for LA-HLH, strongly associated with early mortality risk. This index can be used to stratify the risk levels of patients with LA-HLH and predict their survival outcomes.","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"16 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145008785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comorbidities in Mild WAS/XLT Require Lifelong Follow-Up and Consideration of Definitive Treatment.","authors":"Coralie Mallebranche,Charline Miot,Mickael Alligon,Despina Moshous,Benedicte Neven,Vincent Barlogis,Virginie Courteille,Bénédicte Bruno,Marie Ouachée-Chardin,Dalila Adjaoud,Yves Delneste,Olivier Bouaziz,Capucine Picard,Alain Fischer,Nizar Mahlaoui,Isabelle Pellier, ","doi":"10.1002/ajh.70061","DOIUrl":"https://doi.org/10.1002/ajh.70061","url":null,"abstract":"Loss of function mutations in the gene encoding WASP (Wiskott-Aldrich syndrome protein) result in Wiskott-Aldrich syndrome (WAS) and X-linked thrombocytopenia-XLT (WAS/XLT). The clinical severity of the disease can be assessed using the WAS clinical severity score. Typically, patients with a score of 3 or less at 2 years of age are considered to have mild WAS/XLT disease. However, patients with a low score in the first 2 years of life can still experience life-threatening complications, and there are no agreed guidelines for the management of these patients with mild WAS/XLT. We analyzed data on WAS/XLT patients from the French National Reference Centre for Primary Immunodeficiencies registry. At 10 December 2021, data were available for 261 patients, 170 of whom had mild WAS/XLT. The median age of these patients at last follow-up was 15.8 years (range 2.0-60.4). Overall survival at 40 years was 73% in mild WAS patients versus 65% in severe WAS patients (p = 0.43). In the mild WAS population, prior to Hematopoietic Stem Cell Transplantation or gene therapy, 38.2% of patients progressed to a WAS severity score of 4-5 after the age of 2. Remarkably, no deaths were reported in 45 HSCTs performed since 2010, regardless of initial severity, type and HLA compatibility of the transplant, and age at diagnosis, with a median follow-up of 3.2 years (0-11.5) after transplant. As complications can occur throughout life, our study supports definitive treatment for all patients when available, including those with mild forms.","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"25 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145008786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pure Red Cell Aplasia Associated With Thymic Tumors, a Nationwide Retrospective Study.","authors":"Mylène Hemmer,Sylvain Moinard,Olivier Lambotte,Marion Malphettes,Louis Terriou,Bertrand Lioger,Guillaume Le Guenno,Jean-François Viallard,Marc Michel,Hervé Lobbes","doi":"10.1002/ajh.70068","DOIUrl":"https://doi.org/10.1002/ajh.70068","url":null,"abstract":"Pure red cell aplasia (PRCA) is the most frequent autoimmune cytopenia associated with thymic tumors (TTs). In a nationwide retrospective study, we included 41 patients (22 women, median age 62 years). At PRCA diagnosis, the mean hemoglobin level was 6.6 ± 2.1 g/dL, and the reticulocyte count was 6 ± 5 × 109/L. PRCA was diagnosed before TT (8%, median delay 52 months), simultaneously (46%) or after TT (46%, median delay 34 months). Fourteen patients (34%) had definite Good syndrome. Thymectomy without immunosuppressive treatment provided a single sustainable PRCA response. Twenty-two patients (54%) experienced multiple PRCA relapses (Median 2). When PRCA was present at TT diagnosis, the risk of PRCA relapse was higher (p < 0.01), while TT staging, TT relapse, and Good syndrome were not associated with PRCA relapses. Corticosteroids led to a 77% initial response rate with frequent relapses during taper or at discontinuation. Cyclosporine A provided a 71% response rate. Overall response rates and time to response were similar with corticosteroids and cyclosporine A. Sirolimus led to a 50% response rate in refractory cases. Severe infectious events requiring hospitalizations were frequent (44%). After a mean follow-up of 50 months, five patients (12%) died, three of whom died from TT relapse. Good syndrome was not significantly associated with an increased risk of infection, PRCA relapse, or death. Our findings highlight the severe phenotype of the association of TT and PRCA. While most patients achieve PRCA response under immunosuppressive therapy, high infection incidence and thymoma relapse are responsible for severe morbidity.","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"4 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145008705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hemochromatosis Proteins Hemojuvelin and Homeostatic Iron Regulator in Bone Morphogenetic Protein‐Mediated Hepcidin Regulation and Iron Homeostasis","authors":"Xia Xiao, Gillian A. Moschetta, Samit B. Chowdhury, Sydney Phillips, Niraj Ghatpande, Allison L. Fisher, Yongqiang Xue, Jodie L. Babitt","doi":"10.1002/ajh.70055","DOIUrl":"https://doi.org/10.1002/ajh.70055","url":null,"abstract":"The bone morphogenetic protein (BMP)‐SMAD signaling pathway is central to regulating hepcidin, the master regulator of systemic iron homeostasis. We have previously demonstrated that BMP6, BMP2, and, to a lesser extent, BMP5 are the major ligands contributing to hepcidin and iron homeostasis regulation in vivo. Hemojuvelin (HJV) and homeostatic iron regulator (HFE) are hepcidin modulators that are mutated in hereditary hemochromatosis. Although both HJV and HFE regulate hepcidin, at least partly, by functionally interacting with the BMP–SMAD pathway, the mechanisms are incompletely understood. Notably, both HJV and HFE can regulate hepcidin in a BMP6‐independent manner. To understand whether HJV and HFE influence hepcidin regulation by BMP2 and/or BMP5, we investigated the iron phenotype of mice with combined mutations in endothelial <jats:italic>Bmp2/Hjv</jats:italic> and <jats:italic>Bmp5/Hfe.</jats:italic> We found that endothelial <jats:italic>Bmp2/Hjv</jats:italic> double knockout (KO) mice exhibit more severe hepcidin deficiency and iron overload than single endothelial <jats:italic>Bmp2</jats:italic> or <jats:italic>Hjv</jats:italic> KO mice, similar to previous findings in mice with double endothelial <jats:italic>Bmp2/Hfe</jats:italic> KO and <jats:italic>Bmp6/Hjv</jats:italic> KO, or a functional loss of both <jats:italic>Bmp6</jats:italic> and <jats:italic>Hfe</jats:italic>. Moreover, we found that iron completely fails to induce hepcidin in both endothelial <jats:italic>Bmp2/Hjv</jats:italic> and <jats:italic>Bmp2/Hfe</jats:italic> double KO mice. In contrast, a functional loss of BMP5 does not worsen hemochromatosis in <jats:italic>Hfe</jats:italic> KO mice. Together with other published data, these findings suggest a model whereby BMP2 and BMP6 can signal to hepcidin induction independently of HJV and HFE and vice versa. In contrast, BMP5, HJV, and HFE are all required for iron‐mediated hepcidin regulation in the absence of BMP2 and BMP6.","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"40 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145002772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss-Prone HLA Class I Alleles Inform Outcomes of Early Hematopoietic Cell Transplantation in Acquired Aplastic Anemia.","authors":"Yoshitaka Zaimoku,Hirohito Yamazaki,Minoru Kanaya,Nobuhiro Hiramoto,Ken Ishiyama,Katsuto Takenaka,Makoto Murata,Naoyuki Uchida,Noriko Doki,Ryusuke Yamamoto,Testuya Nishida,Koichi Onodera,Shinichiro Machida,Yoshinobu Kanda,Tetsuya Eto,Keisuke Kataoka,Noboru Asada,Mitsuhiro Itagaki,Mamiko Sakata-Yanagimoto,Fumihiko Ishimaru,Makoto Onizuka,Tatsuo Ichinohe,Yoshiko Atsuta,Yasushi Onishi","doi":"10.1002/ajh.70054","DOIUrl":"https://doi.org/10.1002/ajh.70054","url":null,"abstract":"HLA class I allele loss in acquired aplastic anemia (AA) represents an immune escape from the T cell-mediated pathogenesis. We investigated the impact of loss-prone HLA alleles on the hematopoietic cell transplantation (HCT) outcomes using registry data of 875 Japanese patients with acquired AA. HLA associations were evident exclusively among 399 patients who received HCT within 1 year of the diagnosis, consistent with the predominance of HLA loss in this group. A set of five HLA alleles with the highest propensity for loss (HLA-A*02:01, HLA-A*02:06, HLA-A*31:01, HLA-B*40:02, and HLA-B*54:01) was the strongest predictor of post-transplant survival among all possible allele combinations (5-year survival, 80.3% vs. 54.4%; p < 0.0001), partly due to improved engraftment and pre-transplant conditions. Another set (HLA-A*33:03, HLA-B*07:02, HLA-B*44:03, HLA-B*52:01, and HLA-B*54:01)-less frequently lost in AA and underrepresented in Epstein-Barr virus (EBV)-related diseases outside AA-was associated with an increased risk of post-transplant lymphoproliferative disorders (5-year incidence, 10.2% vs. 1.8%; p = 0.00019), suggesting that the loss of protective alleles against EBV during AA pathogenesis may predispose to EBV-driven lymphoproliferations. These associations were determined by recipient, not donor, HLA. Therefore, specific HLA class I alleles and their potential loss significantly influence the HCT outcomes in acquired AA.","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"33 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144995913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Iron Deficiency in HbSC Disease Treated With Repetitive Phlebotomy Is Associated With Fewer Sickle Cell Disease-Related Complications.","authors":"Marissa J M Traets,Aida S Kidane Gembremeskel,Jennifer Eijkelenboom-Bos,Birgitte A van Oirschot,Sigrid van der Veen,Henk Russcher,Wouter W van Solinge,Mandy N Lauw,Erfan Nur,Bart J Biemond,Marjon H Cnossen,Anita W Rijneveld,Richard van Wijk,Eduard J van Beers,Minke A E Rab","doi":"10.1002/ajh.70045","DOIUrl":"https://doi.org/10.1002/ajh.70045","url":null,"abstract":"","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"15 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144962621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk of Relapse Post Reduced Intensity Conditioning Allogeneic Stem Cell Transplant in Patients With High-Risk Myeloid Neoplasms Based on GvHD Prophylaxis: PTCy Vs. TAC/MTX.","authors":"Khalil Hassan,Anmol Baranwal,Al Rabee Kassis,Jade Braun,Gabriel Bartoo,Robert Wolf,Mehrdad Hefazi,Aasiya Matin,Abhishek Mangoankar,Mithun V Shah,Mark R Litzow,William J Hogan,David Dingli,Hassan B Alkhateeb","doi":"10.1002/ajh.70059","DOIUrl":"https://doi.org/10.1002/ajh.70059","url":null,"abstract":"","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"61 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144962622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sensitivity of Pediatric Myelodysplastic Syndromes With Excess of Blasts With UBTF-TD to Venetoclax/Azacitidine.","authors":"Pietro Merli,Riccardo Masetti,Martina Pigazzi,Katia Girardi,Evelina Miele,Silvia Bresolin,Francesco Baccelli,Jack H Peplinski,Marco Becilli,Valeria Paganelli,Luisa Strocchio,Barbara Buldini,Daria Pagliara,Soheil Meshinchi,Franco Locatelli","doi":"10.1002/ajh.70056","DOIUrl":"https://doi.org/10.1002/ajh.70056","url":null,"abstract":"UBTF-TD has been reported in a significant percentage of childhood MDS-EB and has been associated with inferior survival compared to that of patients with the wild-type gene. We treated three consecutive pediatric patients affected by UBTF-TD MDS-EB with venetoclax and azacitidine (ven/aza) in combination as 28-day cycles on a compassionate use basis three consecutive pediatric patients affected by UBTF-TD MDS-EB as a bridge to allogeneic HSCT. Treatment with ven/aza was well-tolerated, and all patients responded to the ven/aza course, achieving CR with flow-cytometry negativity. All three patients were bridged to myeloablative HSCT. All patients are disease-free and graft-versus-host disease-free at last follow-up. Comprehensive biological characterization of the disease showed (i) high expression of the BCL2 gene, paralleled by a low expression of BCL2A1 and MCL1; (ii) overexpression of both HOXA and HOXB; and (iii) a distinct methylation signature of patients with UBTF-TD myeloid neoplasms.","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"14 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144962623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Triple A Plus (AAA⁺) Survival Prediction Model for Essential Thrombocythemia: Analysis Involving 7308 Patients.","authors":"Ayalew Tefferi, Giuseppe G Loscocco, Lior Rokach, Tamar Tadmor, Priyansh Faldu, Guy Melamed, Hilel Alapi, Maymona Abdelmagid, Rania M Abdelaziz, Muhammad Yousuf, Merry Nakhleh, Animesh Pardanani, Kebede H Begna, Mirnal M Patnaik, Natasha Szuber, Alessandra Carobbio, Tiziano Barbui, Kaaren K Reichard, Rong He, Paola Guglielmelli, Naseema Gangat, Alessandro M Vannucchi","doi":"10.1002/ajh.70065","DOIUrl":"10.1002/ajh.70065","url":null,"abstract":"<p><p>Survival prediction models in essential thrombocythemia (ET) include the International Prognostic Scoring System (IPSET) and the more recently introduced triple-A (AAA) prognostic score. The latter enlists age and absolute neutrophil (ANC) and lymphocyte (ALC) counts as risk variables. In the current study, a Mayo Clinic discovery cohort of 658 patients with ET was used to identify AAA-independent risk variables. Accordingly, multivariable analysis-derived HRs (95% CI) were 15.7 (8.4-29.5) for age > 70 years (8 points); 4.2 (2.3-7.5) for age 50 to 70 years (2 points); 1.8 (1.2-2.5) for ANC ≥ 8 × 10⁹/L (1 point); 1.4 (1.03-1.9) for ALC < 1.7 × 10⁹/L (1 point); 1.8 (1.2-2.6) for absolute monocyte count (AMC) ≥ 0.5 × 10⁹/L (1 point); 1.8 (1.2-2.3) for male sex (1 point); 1.8 (1.3-2.4) for arterial hypertension (1 point); and 1.6 (1.2-2.3) for arterial thrombosis (1 point). HR-weighted scoring enabled a 4-tiered risk classification: ultra-low (0-1 points; N = 94; median survival 42.7 years), low (2-4 points; N = 297; 23 years), intermediate (5 points; N = 66; 17.3 years), and high (6-14 points; N = 201; 10.8 years). Time-dependent predictive performance at 20/25 years favored AAA⁺ (AUC 0.92/0.91) vs. AAA (0.86/0.86) vs. IPSET (0.81/0.84). The AAA⁺ risk model was subsequently validated by two external cohorts from Israel (N = 5968) and Italy (N = 682). In the cohort from Israel, disease-specific mortality was assessed by comparing observed survival to an age- and sex-matched reference population, which suggested near-normal life expectancy in ultra-low risk patients. The current study highlights host-related factors as the primary determinants of longevity in ET and provides a composite risk score (AAA⁺) that is based on complete blood count-derived parameters and host-related factors. Predictive performance of the new model was shown to be superior to that of IPSET and AAA.</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":" ","pages":""},"PeriodicalIF":9.9,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144939539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-Institutional Study of ALK-Positive Large B-Cell Lymphoma: Outcomes in the Era of ALK Inhibitors and Biologically Informed Therapies.","authors":"Suheil Albert Atallah-Yunes, Chijioke C Nze, Rebecca L King, Matthew J Rees, Juan Pablo Alderuccio, Marcus Watkins, Brad S Kahl, Neela Easwar, Samuel Yamshon, Aditya Ravindra, Umar Farooq, Allison C Rosenthal, Javier L Munoz, Estela M Rojas-Neira, Amy A Ayers, Muhamad Alhaj Moustafa, Thomas M Habermann, Thomas E Witzig, Stephen M Ansell, Grzegorz S Nowakowski, Jean L Koff, Christopher R Flowers, Yucai Wang","doi":"10.1002/ajh.70058","DOIUrl":"10.1002/ajh.70058","url":null,"abstract":"<p><p>Anaplastic lymphoma kinase-positive large B-cell lymphoma (ALK+ LBCL) is a rare, aggressive subtype of diffuse large B-cell lymphoma with poor outcomes using standard chemotherapy. In this multi-institutional retrospective study, we analyzed 39 cases of ALK+ LBCL identified at six US academic centers from 2002 to 2024, with treatment including conventional cytotoxic regimens in frontline and biologically informed and nonchemotherapy-based strategies in the relapsed setting. Ninety-two percent of patients received frontline anthracycline-based chemotherapy; 43% received intensified regimens, and 15% underwent upfront autologous stem cell transplantation (ASCT). Despite these approaches, outcomes remained poor. At a median follow-up of 5.4 years, median event-free survival (EFS) was 0.6 years (95% CI, 0.4-0.9), and median overall survival (OS) was 1.5 years (95% CI, 1.3-NR). One- and five-year EFS rates were 28% and 17%, while corresponding OS rates were 72% and 42%, respectively. Advanced stage and high IPI scores were associated with inferior outcomes. Twelve patients received ALK inhibitors, with alectinib showing more durable responses than crizotinib. Lenalidomide and immune checkpoint inhibitors also demonstrated activity, including durable complete responses. Five patients underwent allogeneic stem cell transplantation, with three achieving sustained remission. In conclusion, our findings highlight the limited benefit of chemotherapy, even when intensified or followed by ASCT, and support the integration of biologically targeted therapies, which may have contributed to improved OS in our cohort compared to historical outcomes. Prospective, collaborative studies are needed to better understand disease biology and define optimal use of modern therapies in this rare lymphoma.</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":" ","pages":""},"PeriodicalIF":9.9,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144939519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}