Division of Hematology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
Research Laboratory, 3rd Department of Medicine, Faculty of Medicine, Semmelweis University, Budapest, Hungary.
Transplant Cell Ther. 2022 Dec;28(12):830.e1-830.e7. doi: 10.1016/j.jtct.2022.08.028. Epub 2022 Sep 2.
Autologous hematopoietic stem cell transplantation (HSCT) is often complicated by hemostatic and thrombotic events associated with endothelial cell injury. Thrombotic complications are affected by a disturbed balance between platelets, circulating von Willebrand factor (VWF), and its specific protease, ADAMTS13. HSCT-associated endothelial dysfunction, impaired hemostasis, and inflammation are interrelated processes, and research on the complex interplay of conditioning regimens from engraftment to bone marrow regeneration remains intensive. This prospective observational study comparing lymphoma and multiple myeloma (MM) patients who underwent autologous HSCT explored how platelet count, VWF level, ADAMTS13 activity, and C-reactive protein (CRP) level as potential markers (1) vary in response to therapy, (2) differ between the 2 groups, and (3) correlate with the remission state at 100 days after HSCT. We correlated the quantitative changes in platelet count and levels of VWF, ADAMTS13, and CRP with one another during HSCT and in the remission state in 45 patients with lymphoma and 59 patients with MM who underwent autologous HSCT between 2010 and 2013 at the University of Debrecen. Samples were collected at the start of conditioning chemotherapy, on the day of stem cell transplantation, and at 5, 11, and 100 days following HSCT. CRP levels peaked when platelet counts dropped to a minimum, and these changes were much more pronounced in the lymphoma group. VWF level was the highest, with lower ADAMTS13 activity, at platelet engraftment in both patient groups equally. Diagnostic evidence indicative of thrombotic complications was not found. In the lymphoma group, VWF level prior to conditioning had statistically significant correlations with platelet count, CRP level, and hemoglobin concentration at the time of bone marrow regeneration (P < .001) and during the remission state (P = .034). In the MM group, platelet count before conditioning was correlated with platelet count (P < .001) and white blood cell count (P = .012) at the time of bone marrow regeneration. The statistically significant correlation of the markers at the time of bone marrow regeneration with the preconditioning VWF levels in lymphoma and with the preconditioning platelet counts in MM might indicate the clinical significance of the bone marrow niches of arterioles and megakaryocytes, respectively, where the stem cells are located and regulated. Because preconditioning VWF levels are associated with remission after HSCT in lymphoma patients, VWF should be screened before conditioning, along with the markers used in HSCT protocols, to optimize personalized treatment and reduce therapeutic risks.
自体造血干细胞移植(HSCT)常伴有与内皮细胞损伤相关的止血和血栓形成事件。血栓并发症受血小板、循环 von Willebrand 因子(VWF)及其特异性蛋白酶 ADAMTS13 之间平衡的影响。HSCT 相关的内皮功能障碍、止血受损和炎症是相互关联的过程,关于从植入到骨髓再生的调理方案的复杂相互作用的研究仍然很深入。这项前瞻性观察研究比较了接受自体 HSCT 的淋巴瘤和多发性骨髓瘤(MM)患者,探讨了血小板计数、VWF 水平、ADAMTS13 活性和 C 反应蛋白(CRP)水平作为潜在标志物(1)如何随治疗而变化,(2)在两组之间有何差异,以及(3)与 HSCT 后 100 天的缓解状态有何关联。我们在 2010 年至 2013 年期间,在德布勒森大学,对 45 例接受自体 HSCT 的淋巴瘤患者和 59 例 MM 患者进行了相关性研究,比较了这些患者在 HSCT 期间和缓解状态下血小板计数、VWF、ADAMTS13 和 CRP 水平的定量变化。在接受调理化疗时、干细胞移植当天以及 HSCT 后 5、11 和 100 天采集样本。当血小板计数降至最低时,CRP 水平达到峰值,且在淋巴瘤组中更为明显。两组患者的血小板植入时 VWF 水平最高,ADAMTS13 活性最低。在淋巴瘤组中,在骨髓再生时(P<0.001)和缓解状态时(P=0.034),调理前 VWF 水平与血小板计数、CRP 水平和血红蛋白浓度具有统计学显著相关性。在 MM 组中,调理前的血小板计数与骨髓再生时的血小板计数(P<0.001)和白细胞计数(P=0.012)相关。在淋巴瘤和 MM 中,骨髓再生时标志物与调理前 VWF 水平和血小板计数的统计学显著相关性可能分别表明了位于和受调节的动静脉和巨核细胞骨髓龛的临床意义。由于在淋巴瘤患者中,HSCT 后的缓解与调理前的 VWF 水平相关,因此在调理前,应与 HSCT 方案中使用的标志物一起筛选 VWF,以优化个体化治疗并降低治疗风险。