American Journal of Hematology最新文献

{"title":"Primary Effusion Lymphoma Prognostic Score (PEL-PS): A Validated International Prognostic Score in HIV-Associated Primary Effusion Lymphoma","authors":"Kathryn Lurain,&nbsp;Ramya Ramaswami,&nbsp;Eric Oksenhendler,&nbsp;David Boutboul,&nbsp;Alessia Dalla Pria,&nbsp;Lara Ulrich,&nbsp;Krithika Shanmugasundaram,&nbsp;Thomas S. Uldrick,&nbsp;Mark Bower,&nbsp;Robert Yarchoan,&nbsp;Laurence Gérard,&nbsp;Seth M. Steinberg","doi":"10.1002/ajh.27580","DOIUrl":"10.1002/ajh.27580","url":null,"abstract":"<p>Primary effusion lymphoma (PEL) is an HIV-associated B-cell non-Hodgkin lymphoma (NHL) caused by Kaposi sarcoma herpesvirus (KSHV). There is no validated prognostic model in PEL, and prognosis is thought to be poor compared to other HIV-associated NHL. We derived the PEL-Prognostic score (PEL-PS) from an international real-world training set of 59 patients with HIV-associated PEL who received first-line anthracycline-containing chemotherapy from the HIV and AIDS Malignancy Branch at the National Cancer Institute (NCI) in the United States and the National Center for HIV Malignancy at the Chelsea and Westminster Hospital (CWH) in England from 2000 to 2022. We identified prognostic factors associated with overall survival (OS). In a multivariable Cox model, ECOG ≥ 3 (<i>p</i> = 0.007; hazard ratio [HR] = 4.0 [95% CI: 1.5–11.1]) and hemoglobin &lt; 8 g/dL (<i>p</i> = 0.006; HR = 3.8 [95% CI: 1.5–9.7]) were jointly associated with lower survival probability. The resulting PEL-PS separated patients with no negative prognostic factors (score 0: hemoglobin ≥ 8 g/dL and ECOG ≤ 2, 48.1% of patients) with median OS of 10.6 years versus patients with 1–2 negative prognostic factors (score 1–2: hemoglobin &lt; 8 g/dL and/or ECOG ≥ 3, 51.9% of patients) with median OS of 0.8 years (<i>p</i> &lt; 0.0001). The PEL-PS was then validated in 58 patients with HIV-associated PEL treated with first-line anthracycline-containing chemotherapy at Hôpital Saint-Louis in France over the same period: median OS in patients with PEL-PS 0 was 16.9 years versus 0.6 years in patients with PEL-PS score of 1–2 (<i>p</i> &lt; 0.0001). The PEL-PS identifies patients with good and poor prognosis. Patients with poor prognosis may benefit from novel therapies.</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 3","pages":"393-401"},"PeriodicalIF":10.1,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.27580","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142981660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Level of Clonal Plasma Cells in Hematopoietic Cell Autografts Reflects the Pre-Transplant Bone Marrow Minimal Residual Disease in Multiple Myeloma Patients","authors":"Ondrej Venglar,&nbsp;Eva Radova,&nbsp;David Zihala,&nbsp;Ivana Tvrda,&nbsp;Viktor Kubala,&nbsp;Kamila Kutejova,&nbsp;Ludmila Muronova,&nbsp;Veronika Kapustova,&nbsp;Lucie Broskevicova,&nbsp;Jan Vrana,&nbsp;Tereza Popkova,&nbsp;Jana Mihalyova,&nbsp;Hana Plonkova,&nbsp;Tereza Sevcikova,&nbsp;Michal Kascak,&nbsp;Milan Navratil,&nbsp;Zdenek Koristek,&nbsp;Roman Hajek,&nbsp;Tomas Jelinek","doi":"10.1002/ajh.27590","DOIUrl":"10.1002/ajh.27590","url":null,"abstract":"&lt;p&gt;High-dose melphalan followed by autologous stem cell transplantation (ASCT) remains the standard of care for multiple myeloma (MM) patients. However, hematopoietic cell autografts are often contaminated with aberrant plasma cells (aPC) following CD34+ cell mobilization [&lt;span&gt;1&lt;/span&gt;], making graft MRD (gMRD) assessment potentially valuable. Nevertheless, the clinical significance of gMRD was not fully leveraged so far. It was demonstrated that the gMRD positivity is associated with worse progression-free survival (PFS) and overall survival (OS) [&lt;span&gt;1, 2&lt;/span&gt;]. Recent studies utilizing next generation flow cytometry (NGF) with the limit of detection (LOD) 0.0002% (2 × 10&lt;sup&gt;−6&lt;/sup&gt;) provided similar results, together with predicting worse post-induction response in gMRD positive patients [&lt;span&gt;3-5&lt;/span&gt;]. Therefore, gMRD evaluation holds significant potential for patient benefit. However, there is currently virtually no knowledge about the relationship between gMRD status and pre-ASCT MRD levels in the bone marrow (BM), despite the invasive MRD assessment is increasingly common at this timepoint due to improved first-line therapeutic regimens that induce rapid and deep responses [&lt;span&gt;6&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;To enhance the understanding of gMRD clinical significance, we performed a single-center study involving 99 transplant-eligible MM patients diagnosed between 2019 and 2023. All patients were treated with standard induction therapy, followed by CD34+ cell mobilization, leukapheresis of hematopoietic cell graft, high-dose melphalan, and ASCT (Methods S1–S3). MRD was evaluated in grafts on a day of the first apheresis (gMRD), in BMs one day prior to ASCT (pre-ASCT), and in BMs day +100 after ASCT (post-ASCT) using NGF by EuroFlow protocol (Methods S4, Figure S1).&lt;/p&gt;&lt;p&gt;In total, 44% (44/99) of patients in our cohort were gMRD+ and 56% (55/99) were gMRD-. Both groups were well balanced without any significant differences in terms of age, gender, cytogenetic risk, induction regimens used or number of their cycles (median number of cycles = 4), mobilization regimen, or maintenance status. Notably, patients in the gMRD- group more frequently received anti-CD38 therapy (22% vs. 6.8%), whereas VTd was more common in the gMRD+ group (64% vs. 49%); however, the difference was not statistically significant. ISS I stage was more prevalent in gMRD- group (ISS I, II, III frequency: 47%, 31%, 22%), while ISS II and III were more frequent in gMRD+ cohort (18%, 43%, 39%; &lt;i&gt;p&lt;/i&gt; = 0.009). R-ISS comparison showed similar results (R ISS I, II, III frequency: gMRD- 44%, 51%, 5.5%, gMRD+ 19%, 69%, 12%; &lt;i&gt;p&lt;/i&gt; = 0.033). CD34+ cell yields were significantly higher in gMRD+ group (median, range CD34+ cells × 10&lt;sup&gt;6&lt;/sup&gt;/kg: 13, 9–24 vs. 10, 6–14, &lt;i&gt;p&lt;/i&gt; = 0.013), which might be partially attributed to higher rates of AraC + G-CSF administered in this group (30% vs. 13%), although the difference was not significant (&lt;i&gt;p&lt;/i&gt; = 0.11). Tandem ASCT was mor","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 4","pages":"704-707"},"PeriodicalIF":10.1,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.27590","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142981754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Case of Hodgkin Lymphoma in a Gaucher Disease Patient: Distinguishing Gaucher and Pseudo-Gaucher Cells","authors":"Natalia Scaramellini,&nbsp;Marta Canzi,&nbsp;Elena Cassinerio,&nbsp;Margherita Migone De Amicis,&nbsp;Loredana Pettine,&nbsp;Bruno Fattizzo,&nbsp;Francesca Gaia Rossi,&nbsp;Giorgio Croci,&nbsp;Irene Motta","doi":"10.1002/ajh.27587","DOIUrl":"10.1002/ajh.27587","url":null,"abstract":"&lt;p&gt;A 35-year-old man came to our attention for the suspicion of Gaucher disease (GD). The patient had undergone a bone marrow aspirate and biopsy because of massive splenomegaly (30 cm), severe thrombocytopenia (platelet count 30 000/mm&lt;sup&gt;3&lt;/sup&gt;), and mild anemia [hemoglobin (Hb) 12.1 g/dL] observed in the emergency department, where he presented for acute abdominal pain. Bone marrow biopsy (BMB) revealed foci of fibrosis accompanied by aggregates of CD163+/CD1a− epithelioid histiocytes, featuring a fibrillary, dimly eosinophilic, PASD+ cytoplasm, accounting for 60% of the cellularity. These histological findings were consistent with lysosomal storage disease. GD was then confirmed by beta-glucocerebrosidase activity on dried blood spot (GBA activity 0.4 μmol/L/h, n.v. &gt; 3.5 μmol/L/h) and molecular analysis of the &lt;i&gt;GBA&lt;/i&gt; gene that showed compound heterozygosity c.475C&gt;T/c.1226A&gt;G [p.(Arg159Trp)/p.(Asn409Ser)] mutations. At the time of diagnosis, he also had hyperferritinemia (serum ferritin 1300 ng/mL) with normal transferrin saturation (25%). Substrate reduction therapy with eliglustat was started with hematologic improvement at 1 year: platelet counts 55 000/mm&lt;sup&gt;3&lt;/sup&gt;, Hb 14.1 g/dL, and reduction in the spleen volume (22 cm).&lt;/p&gt;&lt;p&gt;A year and a half later, he complained of night sweats, weight loss of 3 kg over 3 weeks, and fatigue. Blood tests showed slightly microcytic anemia (Hb 10.5 g/dL, mean corpuscular volume 78.7 fL), platelet count three times the previous value (176 000/mm&lt;sup&gt;3&lt;/sup&gt;), even higher values of ferritin (2756 ng/mL), and serologies negative for active infections (HIV CMV, EBV, and Toxoplasma). A total body CT scan showed cervical and thoracic lymphadenopathies up to 4.5 cm and an increase in spleen volume (25 cm). Bone marrow aspirate was negative, while BMB showed foci of Gaucher-type histiocytes, with scattered iron-laden cells, alternated with foci of sclerosis (Figure 1a), with admixed histiocytes, small lymphocytes, eosinophilic granulocytes, and rare scattered, CD30-positive Hodgkin and Reed-Sternberg (HRS) cells (Figure 1b), confirming the clinical suspicion of classical Hodgkin lymphoma (cHL). Interestingly, the diffused and massive macrophage infiltration, which initially masked the rare HRS cells, displayed a double functional phenotype, highlighted through immunohistochemical PD-L1 expression. On the one hand, we observed Gaucher cells with extremely dim PDL-1 intensity [&lt;span&gt;1&lt;/span&gt;]; on the other hand, the tumor microenvironment (TME) of cHL expressed abundant PD-L1 (Figure 1c) [&lt;span&gt;2, 3&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Pseudo-Gaucher cells have been reported in association with a variety of hematological malignancies and are a hallmark of increased cell turnover.&lt;/p&gt;&lt;p&gt;Conversely, in GD, the metabolic defect leads to the accumulation of bioactive glycosphingolipids, which have long been held to drive carcinogenesis. The overall risk for hematological malignancies, particularly B cell neoplasm, is mor","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 4","pages":"697-699"},"PeriodicalIF":10.1,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.27587","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142968303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Recombinant Antibody Against ALK2 Promotes Tissue Iron Redistribution and Contributes to Anemia Resolution in a Mouse Model of Anemia of Inflammation","authors":"Chia-Yu Wang,&nbsp;Emiliano Melgar-Bermudez,&nbsp;Diana Welch,&nbsp;Kevin B. Dagbay,&nbsp;Seemana Bhattacharya,&nbsp;Evan Lema,&nbsp;Tyler Daman,&nbsp;Olivia Sierra,&nbsp;Radina Todorova,&nbsp;Papa Makhtar Drame,&nbsp;Rosa Grenha,&nbsp;Ffolliott M. Fisher,&nbsp;Dena Grayson,&nbsp;Lorena Lerner,&nbsp;Samuel M. Cadena,&nbsp;Jasbir Seehra,&nbsp;Jennifer Lachey","doi":"10.1002/ajh.27578","DOIUrl":"10.1002/ajh.27578","url":null,"abstract":"<p>Patients with chronic inflammation are burdened with anemia of inflammation (AI), where inflammatory cytokines inhibit erythropoiesis, impede erythropoietin production, and limit iron availability by inducing the iron regulator hepcidin. High hepcidin hinders iron absorption and recycling, thereby worsening the impaired erythropoiesis by restricting iron availability. AI management is important as anemia impacts quality of life and potentially affects morbidity and mortality. The bone morphogenetic protein (BMP)-SMAD pathway is crucial for hepcidin regulation. Here, we characterized a research antibody against BMP receptor ALK2, RKER-216, and investigated its mechanism in suppressing hepcidin and improving anemia in acute/chronic inflammation. Additive effects of RKER-216 and recombinant human erythropoietin (rhEPO) on erythropoiesis and iron utilization were also explored. We showed that RKER-216 neutralized ALK2 activity by competing with the binding of BMP6. RKER-216 reduced hepcidin transcription in Hep3B cells, and a subcutaneous dose of RKER-216 at 3 mg/kg suppressed serum hepcidin and increased circulating iron for 3–4 days in wildtype mice. Moreover, RKER-216 decreased hepcidin by inhibiting SMAD1/5/9 signaling in lipopolysaccharide-mediated inflammation and liberated iron from the recycling pathway to alleviate anemia in mice with adenine-induced chronic kidney disease (CKD), a mouse model of AI. Finally, RKER-216 reversed iron-restricted erythropoiesis in CKD mice and supplied the iron requirement for complete resolution of anemia when coupled with rhEPO in addressing AI. Our data support that ALK2 is a key hepcidin regulator and that a neutralizing ALK2 antibody has the potential to restore iron homeostasis as monotherapy or in combination with rhEPO to ameliorate AI.</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 5","pages":"797-812"},"PeriodicalIF":10.1,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.27578","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142940355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Baseline Thrombocytopenia on Early Outcomes in Patients With Acute Venous Thromboembolism","authors":"Ramón Lecumberri,&nbsp;Pedro Ruiz-Artacho,&nbsp;Javier Trujillo-Santos,&nbsp;María Marcos-Jubilar,&nbsp;Montserrat Pérez-Pinar,&nbsp;Isabelle Quéré,&nbsp;Gisela Claver,&nbsp;Juan Gorostidi,&nbsp;Behnood Bikdeli,&nbsp;Manuel Monreal,&nbsp;The RIETE Investigators","doi":"10.1002/ajh.27579","DOIUrl":"10.1002/ajh.27579","url":null,"abstract":"<p>Managing acute venous thromboembolism (VTE) in patients with thrombocytopenia is challenging. We used data from the RIETE registry to investigate the impact of baseline thrombocytopenia on early VTE-related outcomes, depending on the initial presentation as pulmonary embolism (PE) or isolated lower-limb deep vein thrombosis (DVT). From March 2003 to November 2022, 90 418 patients with VTE were included. Thrombocytopenia was categorized as severe (&lt; 50 000/μL, <i>n</i> = 303) or moderate (50 000–99 999/μL, <i>n</i> = 1882). The primary outcome, fatal PE within 15 days after diagnosis, and secondary outcomes, including major bleeding and recurrent VTE, were analyzed using multivariable-adjusted models. Among 52 703 patients with PE, the 15-day case-fatality rates from PE were 5.8% for severe thrombocytopenia, 4.5% for moderate thrombocytopenia, and 1.1% for normal platelet counts. In 37 715 patients with isolated DVT, the cumulative incidence of fatal PE were 0, 0.2%, and 0.05%, respectively. Multivariable analysis revealed a five-fold increase in the risk for fatal PE in severe thrombocytopenia (adjusted HR: 4.89; 95%CI: 2.55–9.39) without significant differences between severe and moderate thrombocytopenia. Thrombocytopenia, either moderate or severe, was also associated with increased risk for both, major bleeding and recurrent VTE at 15 days. Initial presentation with PE substantially worsened prognosis compared to isolated DVT. In conclusion, in patients with acute VTE, thrombocytopenia at baseline was associated with increased risk of early death from PE, a finding that was driven by the subgroup whose initial presentation was PE.</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 3","pages":"375-382"},"PeriodicalIF":10.1,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.27579","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142940034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating Minimal Residual Disease Negativity as a Surrogate Endpoint for Treatment Efficacy in Multiple Myeloma: A Meta-Analysis of Randomized Controlled Trials","authors":"Ioannis Ntanasis-Stathopoulos,&nbsp;Charalampos Filippatos,&nbsp;Anastasios Ntanasis-Stathopoulos,&nbsp;Panagiotis Malandrakis,&nbsp;Efstathios Kastritis,&nbsp;Ourania E. Tsitsilonis,&nbsp;Meletios A. Dimopoulos,&nbsp;Evangelos Terpos,&nbsp;Maria Gavriatopoulou","doi":"10.1002/ajh.27582","DOIUrl":"10.1002/ajh.27582","url":null,"abstract":"<p>This meta-analysis examined the association between minimal residual disease (MRD) negativity and survival outcomes in 15 304 patients with multiple myeloma (MM) enrolled in randomized controlled trials published until June 2, 2024. Overall, there was a significant, negative and strong association between MRD negativity odds ratios and survival hazard ratios (β_PFS = -0.20, <i>p</i> &lt; 0.001, β_OS = -0.12, <i>p</i> = 0.023). These associations remained significant for newly diagnosed patients (β_PFS = -0.35, <i>p</i> &lt; 0.001), and they were consistent but not significant for relapsed/refractory patients (β_PFS = -0.06, <i>p</i> = 0.635). Sustained MRD negativity at 1 year was strongly correlated with prolonged PFS (β_PFS = -0.30, <i>p</i> &lt; 0.001). In conclusion, this comprehensive meta-analysis supports MRD as a surrogate for survival in MM.</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 3","pages":"427-438"},"PeriodicalIF":10.1,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.27582","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142937750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Budesonide, Added to PTCy-Based Regimen, for Prevention of Acute GI GVHD After Allogeneic Stem Cell Transplantation","authors":"Piyanuch Kongtim,&nbsp;Piyatida Chumnumsiriwath,&nbsp;Pongthep Vittayawacharin,&nbsp;Deepa Jeyakumar,&nbsp;Benjamin J. Lee,&nbsp;Jean Doh,&nbsp;Shawn P. Griffin,&nbsp;Richard A. Van Etten,&nbsp;Stefan Ciurea","doi":"10.1002/ajh.27581","DOIUrl":"10.1002/ajh.27581","url":null,"abstract":"<div>\u0000 \u0000 <p>Oral budesonide exerts local effects with negligible systemic glucocorticoid activity, due to rapid first-pass metabolism, therefore, could potentially be efficacious in preventing gastrointestinal (GI) acute GVHD (aGVHD). We explored the use of budesonide, added to posttransplant cyclophosphamide (PTCy), tacrolimus, and mycophenolate mofetil, for prevention of GI aGVHD after allogeneic hematopoietic stem cell transplantation (AHSCT) in a prospective observational study and treated 80 patients with a median age of 53 years (range 19–74). Results were compared with a publicly available CIBMTR dataset of 646 patients who received PTCy-based GVHD prophylaxis (CIBMTR Study # GV17-02) (control). Cumulative incidence (CI) of 3-month grade 2–4 and grade 3–4 aGVHD in the budesonide and control groups were 3.8% vs. 34.4% (<i>p</i> &lt; 0.001) and 1.3% vs. 9.8% (<i>p</i> = 0.029), respectively. One-year GRFS (70.5% vs. 31.5%, <i>p</i> &lt; 0.001), PFS (73.4% vs. 52.8%, <i>p</i> = 0.003), and OS (80.1% vs. 64.2%, <i>p</i> = 0.038) were significantly higher in the budesonide group compared with control group. Propensity score-adjusted analyses showed that the addition of budesonide significantly decreased risk of aGVHD grade 2–4 (HR 0.29, <i>p</i> &lt; 0.001), grade 3–4 (HR 0.12, <i>p</i> = 0.045), and cGVHD (HR 0.22, <i>p</i> &lt; 0.001), which resulted in better GRFS (HR 0.38, <i>p</i> &lt; 0.001), PFS (HR 0.58, <i>p</i> = 0.012), and OS (HR 0.72, <i>p</i> = 0.044). Similar results were found when using propensity score-matched analysis restricted to recipients of haploidentical transplantation. In conclusion, addition of budesonide to PTCy-based GVHD prophylaxis is safe and effective in preventing severe acute GI GVHD with significantly improved GRFS. These results could facilitate transition to peripheral blood grafts for all allogeneic transplant recipients.</p>\u0000 </div>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 3","pages":"383-392"},"PeriodicalIF":10.1,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142935807","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":"Breaking the Bone Marrow Barrier: Peripheral Blood as a Gateway to Measurable Residual Disease Detection in Acute Myelogenous Leukemia","authors":"John T. Butler,&nbsp;William M. Yashar,&nbsp;Ronan Swords","doi":"10.1002/ajh.27586","DOIUrl":"10.1002/ajh.27586","url":null,"abstract":"<p>Acute myeloid leukemia (AML) is a genetically heterogeneous disease with high rates of relapse after initial treatment. Identifying measurable residual disease (MRD) following initial therapy is essential to assess response, predict patient outcomes, and identify those in need of additional intervention. Currently, MRD analysis relies on invasive, serial bone marrow (BM) biopsies, which complicate sample availability and processing time and negatively impact patient experience. Additionally, finding a positive result can generate more questions than answers, causing anxiety for both the patient and the provider. Peripheral blood (PB) evaluation has shown promise in detecting MRD and is now recommended by the European Leukemia Net for AML for certain genetic abnormalities. PB-based sampling allows for more frequent testing intervals and better temporal resolution of malignant expansion while sparing patients additional invasive procedures. In this review, we will discuss the current state of PB testing for MRD evaluation with a focus on next-generation sequencing methodologies that are capable of MRD detection across AML subtypes.</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 4","pages":"638-651"},"PeriodicalIF":10.1,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.27586","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142935108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Limited Benefit of Routine Clinical Follow-Up for Relapse Detection in Diffuse Large B-Cell Lymphoma Patients in Complete Remission Following First-Line Treatment","authors":"Therese Lassen,&nbsp;Torsten H. Nielsen,&nbsp;Annika von Heymann,&nbsp;Lene K. Nielsen,&nbsp;Morten K. Larsen,&nbsp;Anne O. Gang,&nbsp;Christoffer Johansen,&nbsp;Lars M. Pedersen","doi":"10.1002/ajh.27577","DOIUrl":"10.1002/ajh.27577","url":null,"abstract":"<div>\u0000 \u0000 <p>Despite advances in treatment, approximately 15% of patients with diffuse large B-cell lymphoma (DLBCL) who achieve complete remission (CR) after first-line therapy will experience a relapse. However, there is no consensus on the optimal follow-up strategies for detecting relapse after achieving CR. This population-based study, based on the Danish Lymphoma Registry (LYFO), identified a total of 1634 patients diagnosed with DLBCL between 2010 and 2017, including 105 patients who achieved CR following first-line R-CHOP-like therapy and subsequently relapsed. The median follow-up time was 6 years (range 3–8 years). Most cases of relapse were symptomatic (83%), with B symptoms and peripheral lymphadenopathy being the most common. Asymptomatic relapses were identified through physical examination (1%), blood tests (3%), or imaging findings (13%). The proportion of relapses identified outside routine visits was 70%. Only 5% of scheduled routine visits led to a relapse diagnosis, whereas 74% of unscheduled visits initiated by the patient outside routine follow-up resulted in relapse detection. Our findings highlight that systematic, scheduled monitoring of patients in remission after first-line treatment contributes only modestly to the early detection of disease recurrence. Future studies should explore alternative methods of relapse surveillance rather than relying solely on pre-scheduled clinical follow-up.</p>\u0000 </div>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 3","pages":"408-416"},"PeriodicalIF":10.1,"publicationDate":"2025-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142929478","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":"Hyper-CVAD and Sequential Blinatumomab Without and With Inotuzumab in Young Adults With Newly Diagnosed Philadelphia Chromosome-Negative B-Cell Acute Lymphoblastic Leukemia","authors":"Hagop Kantarjian,&nbsp;Nicholas J. Short,&nbsp;Nitin Jain,&nbsp;Fadi G. Haddad,&nbsp;Tapan Kadia,&nbsp;Musa Yilmaz,&nbsp;Alessandra Ferrajoli,&nbsp;Koji Sasaki,&nbsp;Yesid Alvarado,&nbsp;Naveen Pemmaraju,&nbsp;Jayastu Senapati,&nbsp;Rebecca Garris,&nbsp;Farhad Ravandi,&nbsp;Elias Jabbour","doi":"10.1002/ajh.27576","DOIUrl":"10.1002/ajh.27576","url":null,"abstract":"<div>\u0000 \u0000 <p>Adding inotuzumab ozogamicin (InO) to hyper-CVAD and blinatumomab may improve outcomes in newly diagnosed Philadelphia chromosome (Ph)-negative B-cell acute lymphoblastic leukemia (B-ALL). Patients with newly diagnosed B-ALL received up to four cycles of hyper-CVAD followed by four cycles of blinatumomab. Beginning with patient #39, InO 0.3 mg/m² was added on Days 1 and 8 to two cycles of high-dose methotrexate and cytarabine, and two cycles of blinatumomab. The primary endpoint was the relapse-free survival (RFS) rate. Seventy-five patients were treated (median age of 33 years; range, 18–59), of whom 37 (49%) received hyper-CVAD with blinatumomab and InO (cohort 2). Measurable residual disease (MRD) negativity by next-generation sequencing (sensitivity: 1 × 10⁻⁶) was achieved in 79% of patients in cohort 2. The median follow-up was 44 months (range, 13–90) overall, and 26 months (range, 8–39) in cohort 2. For the entire cohort, the estimated 3-year RFS rate was 82% and the 3-year overall survival rate was 90%. These rates were 90% versus 74% (<i>p</i> = 0.06) and 100% versus 82% (<i>p</i> = 0.01) in patients who did or did not receive InO, respectively. No sinusoidal obstruction syndrome was observed. In summary, hyper-CVAD with blinatumomab and InO improved the outcomes of patients with newly diagnosed B-ALL.</p>\u0000 </div>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 3","pages":"402-407"},"PeriodicalIF":10.1,"publicationDate":"2025-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142929324","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}