Zekhethelo A Mkhwanazi, Tawanda M Nyambuya, Edwig Shingenge, Bongani B Nkambule
{"title":"Adaptive immune and platelet activation during the maintenance phase of therapy in adults with B cell acute lymphoblastic leukemia.","authors":"Zekhethelo A Mkhwanazi, Tawanda M Nyambuya, Edwig Shingenge, Bongani B Nkambule","doi":"10.1080/09537104.2026.2636463","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Maintenance therapy is an integral component of treatment for B cell acute lymphoblastic leukemia (B-ALL) and has demonstrated clinical efficacy. However, features of immune activation and an increased thrombotic risk may persist beyond the induction phase of treatment. The mechanisms underlying immune activation during the maintenance phase of B-ALL remain unclear. Therefore, this study aimed to evaluate immune activation and thrombotic risk in adult patients with B-ALL undergoing maintenance therapy.</p><p><strong>Method: </strong>This prospective study was conducted at Windhoek Central Hospital and Katutura State Hospital in Namibia. Adult patients with B-ALL receiving maintenance therapy (<i>n</i> = 16) and eighteen controls (<i>n</i> = 18) were enrolled. Plasma concentrations of D-dimer, thrombin, and platelet factor 4 (PF-4) were quantified using enzyme-linked immunosorbent assay and the surface expression of immune checkpoint and activation markers on CD4<sup>+</sup> T cells, B lymphocytes, and platelets were measured using flow cytometry.</p><p><strong>Results: </strong>Patients with B-ALL demonstrated elevated thrombin (<i>p</i> = .01) and PF4 (<i>p</i> = .02) concentrations compared with healthy controls. In addition, the expression of the activation marker CD69 (<i>p</i> < .001), and immune checkpoints PD-L1 (<i>p</i> < .001) and CTLA-4 (<i>p</i> < .001) were increased on the surface of CD4<sup>+</sup> T cells. While PD-1 expression remained comparable between the groups (<i>p</i> = .90). On B lymphocytes, CD69 expression levels were similar between groups (<i>p</i> = .11). Whereas the levels of PD-L1 (<i>p</i> < .001) and CTLA-4 (<i>p</i> = .02) were elevated. Notably, PD-1 expression was reduced in patients with B-ALL (<i>p</i> = .02). The expression of CD62P was increased in patients with B-ALL when compared with controls (<i>p</i> < .001).</p><p><strong>Conclusion: </strong>Adult patients with B-ALL undergoing maintenance therapy exhibits increased lymphocyte and platelet activation, which may be associated with an elevated thrombotic risk despite normal D-dimer levels.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"37 1","pages":"2636463"},"PeriodicalIF":3.1000,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Platelets","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/09537104.2026.2636463","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2026/3/9 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Maintenance therapy is an integral component of treatment for B cell acute lymphoblastic leukemia (B-ALL) and has demonstrated clinical efficacy. However, features of immune activation and an increased thrombotic risk may persist beyond the induction phase of treatment. The mechanisms underlying immune activation during the maintenance phase of B-ALL remain unclear. Therefore, this study aimed to evaluate immune activation and thrombotic risk in adult patients with B-ALL undergoing maintenance therapy.
Method: This prospective study was conducted at Windhoek Central Hospital and Katutura State Hospital in Namibia. Adult patients with B-ALL receiving maintenance therapy (n = 16) and eighteen controls (n = 18) were enrolled. Plasma concentrations of D-dimer, thrombin, and platelet factor 4 (PF-4) were quantified using enzyme-linked immunosorbent assay and the surface expression of immune checkpoint and activation markers on CD4+ T cells, B lymphocytes, and platelets were measured using flow cytometry.
Results: Patients with B-ALL demonstrated elevated thrombin (p = .01) and PF4 (p = .02) concentrations compared with healthy controls. In addition, the expression of the activation marker CD69 (p < .001), and immune checkpoints PD-L1 (p < .001) and CTLA-4 (p < .001) were increased on the surface of CD4+ T cells. While PD-1 expression remained comparable between the groups (p = .90). On B lymphocytes, CD69 expression levels were similar between groups (p = .11). Whereas the levels of PD-L1 (p < .001) and CTLA-4 (p = .02) were elevated. Notably, PD-1 expression was reduced in patients with B-ALL (p = .02). The expression of CD62P was increased in patients with B-ALL when compared with controls (p < .001).
Conclusion: Adult patients with B-ALL undergoing maintenance therapy exhibits increased lymphocyte and platelet activation, which may be associated with an elevated thrombotic risk despite normal D-dimer levels.
期刊介绍：
Platelets is an international, peer-reviewed journal covering all aspects of platelet- and megakaryocyte-related research.
Platelets provides the opportunity for contributors and readers across scientific disciplines to engage with new information about blood platelets. The journal’s Methods section aims to improve standardization between laboratories and to help researchers replicate difficult methods.
Research areas include:
Platelet function
Biochemistry
Signal transduction
Pharmacology and therapeutics
Interaction with other cells in the blood vessel wall
The contribution of platelets and platelet-derived products to health and disease
The journal publishes original articles, fast-track articles, review articles, systematic reviews, methods papers, short communications, case reports, opinion articles, commentaries, gene of the issue, and letters to the editor.
Platelets operates a single-blind peer review policy. Authors can choose to publish gold open access in this journal.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
