Papadopoulou Anastasia, Koukoulias Kiriakos, Alvanou Maria, Papadopoulos Vassilios K, Bousiou Zoe, Kalaitzidou Vasiliki, Kika Fotini S, Papalexandri Apostolia, Mallouri Despina, Batsis Ioannis, Sakellari Ioanna, Anagnostopoulos Achilles, Yannaki Evangelia
Hematology Department-Hematopoietic Cell Transplantation Unit, Gene and Cell Therapy Center "George Papanikolaou" Hospital Thessaloniki Greece.
Department of Genetics, Development and Molecular Biology, School of Biology Aristotle University of Thessaloniki Thessaloniki Greece.
EJHaem. 2021 Jun 1;2(3):428-439. doi: 10.1002/jha2.175. eCollection 2021 Aug.
Despite routine post-transplant viral monitoring and pre-emptive therapy, viral infections remain a major cause of allogeneic hematopoietic cell transplantation-related morbidity and mortality.
We here aimed to prospectively assess the kinetics and the magnitude of cytomegalovirus-(CMV), Epstein Barr virus-(EBV), and BK virus-(BKV)-specific T cell responses post-transplant and evaluate their role in guiding therapeutic decisions by patient risk-stratification.
The tri-virus-specific immune recovery was assessed by Elispot, in 50 consecutively transplanted patients, on days +20, +30, +60, +100, +150, +200 post-transplant and in case of reactivation, weekly for 1 month.
The great majority of the patients experienced at least one reactivation, while over 40% of them developed multiple reactivations from more than one of the tested viruses, especially those transplanted from matched or mismatched unrelated donors. The early reconstitution of virus-specific immunity (day +20), favorably correlated with transplant outcomes. Εxpanding levels of CMV-, EBV-, and BKV-specific T cells (VSTs) post-reactivation coincided with decreasing viral load and control of infection. Certain cut-offs of absolute VST numbers or net VST cell expansion post-reactivation were determined, above which, patients with CMV or BKV reactivation had >90% probability of complete response (CR).
Immune monitoring of virus-specific T-cell reconstitution post-transplant may allow risk-stratification of virus reactivating patients and enable patient-tailored treatment. The identification of individuals with high probability of CR will minimize unnecessary overtreatment and drug-associated toxicity while allowing candidates for pre-emptive intervention with adoptive transfer of VSTs to be appropriately selected.
尽管进行了常规的移植后病毒监测和抢先治疗，但病毒感染仍然是异基因造血细胞移植相关发病和死亡的主要原因。
我们旨在前瞻性评估移植后巨细胞病毒（CMV）、EB病毒（EBV）和BK病毒（BKV）特异性T细胞反应的动力学和强度，并通过患者风险分层评估其在指导治疗决策中的作用。
通过酶联免疫斑点法（Elispot）对50例连续移植患者在移植后第20、30、60、100、150、200天评估三病毒特异性免疫恢复情况，若出现病毒再激活，则在1个月内每周评估一次。
绝大多数患者至少经历了一次再激活，其中超过40%的患者出现了来自一种以上检测病毒的多次再激活，尤其是那些接受匹配或不匹配无关供体移植的患者。病毒特异性免疫的早期重建（第20天）与移植结果呈正相关。再激活后巨细胞病毒、EB病毒和BKV特异性T细胞（VST）水平的升高与病毒载量的降低和感染的控制相一致。确定了再激活后绝对VST数量或净VST细胞扩增的某些临界值，高于这些临界值，巨细胞病毒或BKV再激活的患者完全缓解（CR）的概率>90%。
移植后对病毒特异性T细胞重建进行免疫监测可以对病毒再激活患者进行风险分层，并实现个体化治疗。识别CR可能性高的个体将最大限度地减少不必要的过度治疗和药物相关毒性，同时允许适当选择可通过VST过继转移进行抢先干预的候选者。
