{"title":"Prognostic impact and clinical value of low levels of flow cytometric MRD at the end of induction in childhood B-lineage acute lymphoblastic leukemia: Results of study ALL-MB 2015","authors":"Alexander Popov, Guenter Henze, Julia Roumiantseva, Oleg Budanov, Ekaterina Mikhailova, Polina Lavrova, Tatiana Verzhbitskaya, Zhan Permikin, Grigory Tsaur, Svetlana Lagoyko, Liudmila Zharikova, Natalia Miakova, Dmitry Litvinov, Larisa Fechina, Galina Novichkova, Alexander Karachunskiy","doi":"10.1002/hem3.70162","DOIUrl":"https://doi.org/10.1002/hem3.70162","url":null,"abstract":"<p>Monitoring of minimal residual disease (MRD) using multicolor flow cytometry (MFC-MRD) or PCR (PCR-MRD) is currently the most powerful tool for assessing response to treatment in childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL).<span><sup>3</sup></span> Both methods are typically used at the end of induction (EOI) to identify patients with slow leukemia elimination.<span><sup>1, 3, 4</sup></span> Traditionally, PCR-MRD is considered more sensitive compared to MFC-MRD, as the reliable positivity threshold is at least one log lower (10<sup>−5</sup> vs. 0.01%).<span><sup>2, 5, 6</sup></span> Recent improvements in the MFC-MRD method now also allow a higher sensitivity with a cut-off value of 0.001%.<span><sup>7, 8</sup></span> The aim of the present study was to investigate whether MFC-MRD positivity at EOI at particularly low levels (between 0.001% and 0.01%) could provide additional clinically valuable information in children with BCP-ALL treated with a reduced intensity protocol.</p><p>Between December 2014 and December 2021, 4925 consecutive pediatric patients (aged 1–18 years) with Ph-negative BCP-ALL in Russia and Belarus were enrolled in the ALL-MB 2015 Moscow-Berlin study (NCT03390387). Patients were categorized into risk groups if they met the criteria listed in Supporting Information S2: Table 1, and then assigned to treatment groups (TG), as shown in Supporting Information S2: Table 2. The therapy courses are shown in Supporting Information S2: Figure 1. Briefly, all patients in the TG A, B, C, D1-2, 1221-SR, and 1221-IR received induction therapy consisting of dexamethasone, vincristine, PEG asparaginase, daunorubicin, and triple intrathecal therapy, followed by three cycles of consolidation (six cycles for TG C) and maintenance therapy (Supporting Information S2: Table 3). Patients who did not achieve remission at EOI (day 36 of therapy) were finally stratified into TG E (Supporting Information S2: Table 2).</p><p>The MFC-MRD monitoring study was initially conducted on patients treated in facilities linked to the MFC laboratories of the Moscow-Berlin Group Flow Network.<span><sup>9</sup></span> In March 2020, the study was extended to all Russian patients who routinely submitted their samples to the central laboratories. The bone marrow samples were taken at the EOI, as previously determined to be the most meaningful time point for the Moscow-Berlin Group protocols.<span><sup>10</sup></span> The characteristics of the MFC-MRD study patients are listed in Supporting Information S2: Table 4.</p><p>MFC-MRD was assessed in two Russian laboratories using a well-harmonized approach.<span><sup>9</sup></span> Both laboratories used the same MFC method, which is described in detail in the Supporting Information. Both laboratories had participated in the AIEOP-BFM-QA system<span><sup>11</sup></span> and in intra-group performance tests.<span><sup>12</sup></span> The high degree of harmonization and the sufficient cellularity o","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 7","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70162","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144551055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
HemaSpherePub Date : 2025-07-03DOI: 10.1002/hem3.70169
William G. Dunn, Isabella Withnell, Muxin Gu, Pedro Quiros, Sruthi Cheloor Kovilakam, Ludovica Marando, Sean Wen, Margarete A. Fabre, Irina Mohorianu, Dragana Vuckovic, George S. Vassiliou
{"title":"CHIC: A machine learning framework for inferring the presence of high-risk clonal hematopoiesis using complete blood count data from 431,531 UK Biobank participants","authors":"William G. Dunn, Isabella Withnell, Muxin Gu, Pedro Quiros, Sruthi Cheloor Kovilakam, Ludovica Marando, Sean Wen, Margarete A. Fabre, Irina Mohorianu, Dragana Vuckovic, George S. Vassiliou","doi":"10.1002/hem3.70169","DOIUrl":"https://doi.org/10.1002/hem3.70169","url":null,"abstract":"<p>Clonal hematopoiesis (CH) is an age-related phenomenon that arises when a hematopoietic stem cell acquires a somatic driver mutation (i.e., one that increases its fitness), leading to clonal expansion of the cell and its progeny.<span><sup>1, 2</sup></span> Large population-based studies have revealed that the most commonly mutated genes in CH are involved in epigenetic regulation (<i>DNMT3A</i>, <i>TET2</i>, and <i>ASXL1</i>), signal transduction (<i>JAK2</i>, <i>GNB1</i>), DNA damage response and apoptosis (<i>TP53</i>, <i>PPM1D</i>), and splicing (<i>SF3B1</i>, <i>SRSF2</i>, and <i>U2AF1</i>).<span><sup>1-6</sup></span> The prevalence of CH increases with advancing age to affect at least 20% of those over 70 years, in whom the phenomenon is almost universally detectable when deep sequencing approaches are employed.<span><sup>1-6</sup></span></p><p>A hallmark of CH is the associated increased risk of incident myeloid neoplasms (MNs), a molecularly heterogeneous group of blood cancers that include acute myeloid leukemia, myelodysplastic syndromes (MDSs), and myeloproliferative neoplasms (MPNs). Recent advances have led to the development of predictive tools that estimate the risk of progression from CH to MN,<span><sup>7, 8</sup></span> such that individuals at high risk can be identified and prioritized for clinical follow-up. As CH precedes the development of MN by several years,<span><sup>1-3, 7, 9, 10</sup></span> this provides a window during which high-risk clones could be intercepted and targeted to avert or delay the development of MN.</p><p>A key impediment to prospective myeloid cancer prevention programs is the lack of a scalable test to identify individuals with CH. At present, CH is identified by next-generation sequencing (NGS) of blood DNA targeted to a panel of genes recurrently mutated in MN. However, NGS is not performed in routine clinical practice and is impractical and costly to perform at scale. An alternative approach is to leverage low-cost, scalable, routine clinical tests to identify the individuals most likely to harbor CH, who can then be prioritized for sequencing. The complete blood count (CBC) is an inexpensive, routine clinical test, and CBC indices such as the red cell distribution width (RDW) and mean cell volume are known to be associated with progression from CH to MN.<span><sup>10</sup></span> We therefore sought to explore whether tree-based machine learning (ML) models could detect individuals with CH based on CBC features, through analysis of paired CBC and whole-exome sequencing (WES) data from 431,531 United Kingdom Biobank (UKB) participants.</p><p>After excluding those with missing CBC data (<i>n</i> = 32,670), missing WES data (<i>n</i> = 36,368), or a prevalent diagnosis of a hematological malignancy (<i>n</i> = 1840), CH variant allele frequency [VAF] ≥2%) was identified in 20,860/431,531 (4.8%) UKB participants, of whom 7637 (36.6%) had large clone CH (VAF ≥10%; Figure 1A, Table S1). Using this ","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 7","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70169","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144551145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"NK-type large granular lymphocyte leukemia comes of age","authors":"Gianpietro Semenzato, Antonella Teramo, Gregorio Barilà, Giulia Calabretto, Elisa Rampazzo, Elena Buson, Renato Zambello","doi":"10.1002/hem3.70161","DOIUrl":"https://doi.org/10.1002/hem3.70161","url":null,"abstract":"<p>NK-large granular lymphocyte leukemia (NK-LGLL) is a lymphoid malignancy driven by constitutive activation of cellular pathways and chronic inflammation, underscoring the central role of the microenvironment in the disease's pathogenesis. Patients with NK-LGLL typically present with an expansion of mature NK cells displaying large granular lymphocyte morphology, a restricted killer Immunoglobulin-like receptor pattern and genetic lesions, including <i>TET2</i>, <i>CCL22</i>, and <i>STAT3</i> mutations. NK-LGLL generally follows an indolent clinical course and rarely progresses to a stage requiring treatment. The rarity of the disease has significantly hampered precise diagnosis, a deeper understanding of its pathogenesis, the assessment of appropriate clinical trials, and even its classification. This review aims to present the latest insights into genetic, biological, and clinical features of this disorder. In particular, recent advances in genetics and epigenetics, along with emerging knowledge into the role of microenvironment, have uncovered new vulnerabilities in leukemic cells. These findings may have a meaningful impact on defining genomic-driven disease subsets and hold promise for improving outcomes in large granular lymphocyte leukemia patients through the development of personalized, innovative therapies.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 6","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70161","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144482200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
HemaSpherePub Date : 2025-06-25DOI: 10.1002/hem3.70174
Helen Rooks, Cecilia Ng, Spyros Oikonomopoulos, Sara El Hoss, Charles Turner, Kar Lok Kong, Syed Mian, Yvonne Daniel, Oyesola O. Ojewunmi, John Brewin, David Rees, Ghulam J. Mufti, Jiannis Ragoussis, John Strouboulis, Stephan Menzel
{"title":"Fetal-hemoglobin-expressing red blood cells (“F cells”) consist of three distinct types as revealed by single-cell transcriptomic analysis of circulating reticulocytes","authors":"Helen Rooks, Cecilia Ng, Spyros Oikonomopoulos, Sara El Hoss, Charles Turner, Kar Lok Kong, Syed Mian, Yvonne Daniel, Oyesola O. Ojewunmi, John Brewin, David Rees, Ghulam J. Mufti, Jiannis Ragoussis, John Strouboulis, Stephan Menzel","doi":"10.1002/hem3.70174","DOIUrl":"https://doi.org/10.1002/hem3.70174","url":null,"abstract":"<p>Human erythropoiesis switches from expressing fetal hemoglobin (HbF, with an α<sub>2</sub>γ<sub>2</sub> chain composition) to adult hemoglobin (HbA-α<sub>2</sub>β<sub>2</sub> and HbA<sub>2</sub>-α<sub>2</sub>δ<sub>2</sub>) around birth. Some red blood cells seem to evade a complete switch, retaining significant amounts of HbF throughout life. These have been termed F cells<span><sup>1</sup></span> and usually constitute between 1% and 7% of circulating erythrocytes. Little is known about when and how this apparent red-cell sublineage<span><sup>2</sup></span> diverges from common erythropoiesis, but F cells have attracted considerable interest for two main reasons. First, they show resistance to the adverse effects of the sickle cell and β-thalassemia mutations by slowing the rate of the polymerization of sickle hemoglobin (HbS) in sickle cell disease (SCD) and reducing the excess of α-globin in β-thalassemia. Therefore, boosting HbF expression is the target of many therapeutic strategies for these conditions. It is also the main mechanism of action of hydroxyurea, a disease-modifying agent in SCD, and to a lesser extent, thalassemia. Second, F cells are potentially useful biomarkers because they become more abundant in acute erythropoietic stress, some malignant hematological disorders, and during bone marrow regeneration.<span><sup>3</sup></span> Thus, their study promises to shed light on how erythropoiesis transitions between normal and abnormal conditions.</p><p><i>Investigating gene expression on a single-cell level</i> offers insight into the biology of heterogeneous cell populations, such as differences between erythroid cells containing high levels of HbF (F cells) and those with little or no HbF (non-F cells). Reticulocytes, as the immediate precursors to mature erythrocytes, also encompass a distinct HbF-containing fraction, “F reticulocytes.”<span><sup>4</sup></span> They still contain significant amounts of messenger RNA (mRNA), allowing us to dissect red blood cell heterogeneity in reticulocytes from three healthy volunteers and one patient with sickle cell anemia (HbSS, ethics board approval IRAS#92493 and 296705). To get initial insight into underlying biology, we also studied BEL-A cells, a human erythroid cell line with a globin expression profile matching adult erythropoiesis.<span><sup>5</sup></span></p><p>We used the BD Rhapsody single-cell multi-omics platform with a panel of 118 genes that excluded α- and β-globin genes (to prevent their transcripts from overwhelming the data) alongside seven erythroid surface protein markers. In brief, after Percoll enrichment from a fresh (<1 h) peripheral-blood sample, reticulocytes (CD71+ erythrocytes) were flow-sorted to >95% purity, then labeled with oligonucleotide-conjugated antibodies for (“AbSeq”) CD71, CD36, CD45, CD44, CD34, CD235a, and CD49d. About 25,000 cells were captured into single-cell cartridge wells and provided with a bead containing oligonucleotide tags for th","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 6","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70174","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144482202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
HemaSpherePub Date : 2025-06-17DOI: 10.1002/hem3.70158
Kyung Taek Hong, Jung Yoon Choi, Hyery Kim, Ho Joon Im, Seung Min Hahn, Chuhl Joo Lyu, Hee Young Ju, Keon Hee Yoo, Eu Jeen Yang, Sung-Soo Yoon, Hyeon Jin Park, Hyoung Soo Choi, Hee Won Chueh, Deok-Hwan Yang, Joon Ho Moon, Jae Min Lee, Jung-Hee Lee, Jeong-A Kim, Jong-Ho Won, Hyoung Jin Kang
{"title":"Comparable outcomes for pediatric acute lymphoblastic leukemia patients receiving conditioning with total body irradiation or chemotherapy: A nationwide, Korean registry-based study","authors":"Kyung Taek Hong, Jung Yoon Choi, Hyery Kim, Ho Joon Im, Seung Min Hahn, Chuhl Joo Lyu, Hee Young Ju, Keon Hee Yoo, Eu Jeen Yang, Sung-Soo Yoon, Hyeon Jin Park, Hyoung Soo Choi, Hee Won Chueh, Deok-Hwan Yang, Joon Ho Moon, Jae Min Lee, Jung-Hee Lee, Jeong-A Kim, Jong-Ho Won, Hyoung Jin Kang","doi":"10.1002/hem3.70158","DOIUrl":"https://doi.org/10.1002/hem3.70158","url":null,"abstract":"<p>Acute lymphoblastic leukemia (ALL) is the predominant malignancy in pediatric patients, and allogeneic hematopoietic stem cell transplantation (HSCT) plays a critical role in high-risk cases. However, real-world nationwide data comparing the outcomes of conditioning regimens are limited. This nationwide registry-based study analyzed data from 270 Korean pediatric patients with high-risk or relapsed ALL who underwent their first allogeneic HSCT with myeloablative conditioning. Among all analyzed patients, 118 received total body irradiation-based conditioning (MAC-TBI) and 152 received chemotherapy-based conditioning (MAC-Chemotherapy), of whom 96.6% underwent busulfan-based regimens. MAC-TBI recipients were older at diagnosis and at HSCT. No significant differences were observed between groups in neutrophil or platelet engraftment times, or infused CD34+ cell doses. Acute graft-versus-host disease (GVHD) incidences (grades II–IV and III–IV) were comparable, although chronic GVHD incidence tended to be lower in the MAC-Chemotherapy group (21.0% vs. 31.1%, P = 0.072). Additionally, the 5-year event-free survival (EFS) rates for MAC-TBI versus MAC-Chemotherapy were 73.7% and 69.8% (P = 0.827), respectively; the 5-year overall survival (OS) rates were 76.3% and 80.2% (P = 0.941), respectively, indicating that conditioning regimen did not significantly impact survival. Pediatric disease risk index, recent HSCT era, haploidentical donor type, and pre-transplant disease status independently influenced EFS and OS, whereas anti-thymocyte globulin administration significantly improved moderate-to-severe chronic GVHD, leukemia-free survival. This nationwide real-world analysis demonstrated comparable outcomes between myeloablative TBI-based and chemotherapy-based conditioning regimens in pediatric patients with ALL. These findings may inform the development of improved treatment strategies for this patient population.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 6","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70158","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144300183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
HemaSpherePub Date : 2025-06-17DOI: 10.1002/hem3.70157
Adama Ladu, Stephen P. Hibbs
{"title":"Examining the secret life of the spleen in sickle cell disease","authors":"Adama Ladu, Stephen P. Hibbs","doi":"10.1002/hem3.70157","DOIUrl":"https://doi.org/10.1002/hem3.70157","url":null,"abstract":"<p>The spleen is a complex and often misunderstood organ, particularly in the context of sickle cell disease (SCD). Although hyposplenism is commonly observed in SCD, it can paradoxically coexist with features of hypersplenism, splenomegaly, and acute splenic sequestration. This apparent contradiction demonstrates the multifaceted nature of splenic function, where different physiological roles may be variably affected by disease. If clinicians could accurately measure splenic function and correlate clinical outcomes in SCD, it could facilitate risk-adapted approaches to infection prophylaxis – and potentially other complications linked to splenic dysfunction.</p><p>In this article, we survey both the established and emerging roles of the spleen and current methods of assessing splenic function. We then discuss why these assessments could be valuable in the management of SCD, particularly in resource-constrained settings, and review the predictive value of current tools.</p><p>The spleen is the largest organ of the lymphatic system and plays an important role in both immune defense and regulation of blood cell quality. One of its primary functions is the phagocytic filtration of the bloodstream, enabling the clearance of pathogens and cellular debris. It also contributes to adaptive immunity through the production of opsonising antibodies, which are particularly important for eliminating encapsulated bacteria (e.g., <i>Streptococcus pneumoniae</i>) and intracellular parasites (e.g., <i>Plasmodium falciparum</i>, <i>Babesia</i> spp).</p><p>Beyond an immune role, the spleen contributes to maintaining the quality of circulating red cells. It removes senescent erythrocytes from the bloodstream and recycles their iron for reuse in erythropoiesis. This filtration function may help explain the association between hyposplenism and vascular complications, such as the increased incidence of thrombotic events observed after splenectomy. The spleen also acts as a physiological reservoir, storing extra blood to release in times of increased demand, such as severe blood loss or intense physical exertion. A striking example of this reservoir function is observed in the Bajau people – commonly known as “sea nomads” – who have markedly enlarged spleens that enable them to dive to depths of up to 200 feet and remain underwater for as long as 13 minutes.<span><sup>1</sup></span></p><p>Emerging research has revealed that the spleen engages in bidirectional communication with other organs.<span><sup>2</sup></span> A notable example is the gut–spleen axis, in which the gut microbiota modulates splenic immune activity, while splenic cytokines reciprocally influence bowel inflammation. Interventions such as probiotics, dietary modification, and fecal microbiota transplantation are under investigation for their potential to modulate this gut-spleen interaction.<span><sup>3</sup></span></p><p>Several modalities can be employed to evaluate splenic function,<span><sup>4</sup","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 6","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70157","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144300184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
HemaSpherePub Date : 2025-06-15DOI: 10.1002/hem3.70159
Patrick Born, David Fandrei, Song Yau Wang, Carmen Perez-Fernandez, Luise Fischer, Jule Ussmann, Enrica Bach, Sandra Hoffmann, Klaus H. Metzeler, Marco Herling, Carmen Herling, Madlen Jentzsch, Andreas Boldt, Sabine Seiffert, Ronny Baber, Heike Weidner, Georg-Nikolaus Franke, Timm Denecke, Osama Sabri, Uwe Platzbecker, Vladan Vucinic, Hans Jonas Meyer, Lars Kurch, Maximilian Merz
{"title":"Prognostic significance of PET/CT for CAR T cell therapy in relapsed/refractory multiple myeloma","authors":"Patrick Born, David Fandrei, Song Yau Wang, Carmen Perez-Fernandez, Luise Fischer, Jule Ussmann, Enrica Bach, Sandra Hoffmann, Klaus H. Metzeler, Marco Herling, Carmen Herling, Madlen Jentzsch, Andreas Boldt, Sabine Seiffert, Ronny Baber, Heike Weidner, Georg-Nikolaus Franke, Timm Denecke, Osama Sabri, Uwe Platzbecker, Vladan Vucinic, Hans Jonas Meyer, Lars Kurch, Maximilian Merz","doi":"10.1002/hem3.70159","DOIUrl":"https://doi.org/10.1002/hem3.70159","url":null,"abstract":"<p>PET/CT plays an important role in staging of multiple myeloma (MM) and detecting extramedullary disease (EMD); however, its role in patients treated with commercially available CAR T cell therapies is unclear. We evaluated 61 patients treated with CAR T cell products. In 53 patients, PET/CT was available before CAR T infusion, and 43 had follow-up PET/CT on day 30. Findings from PET/CT were correlated to (CAR) T single-cell dynamics, fitness and T cell receptor diversity after infusion, and serological markers of tumor burden and inflammation. Patients with bone-independent EMD had inferior median progression-free survival (PFS: 3 vs. 15 months, <i>p</i> = 0.01). Univariate and multivariate analysis showed that EMD but not the number of lesions or metabolic tumor volume (MTV) were associated with inferior PFS. High MTV was connected to higher baseline sBCMA and Interleukin-6 levels, but not associated with hampered CAR T cell expansion or decreased fitness of the bystander T cell compartment. Follow-up PET/CTs identified patients with metabolic complete remissions, which were associated with better PFS. PET/CT identifies patients with high risk of relapse after CAR T cell therapy.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 6","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70159","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144292652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}