2024年 · 第06卷第01期

Letermovir is a specific inhibitor of cytomegalovirus (CMV) terminase complex. Several studies have reported that letermovir can effectively prevent CMV activation after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We aimed to identify the efficacy and safety of letermovir prophylaxis for CMV infection after allo-HSCT with a systemic review and meta-analysis. A literature search was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. PubMed and Embase databases were searched. A total of 28 studies were included. The incidence of CMV activation at 14 weeks after HSCT was 0.10 (95% confidence interval [CI], 0.06–0.18), which was 0.10 (95% CI, 0.04–0.21) and 0% in adult and children (2 studies were included and both of them were 0%). In addition, the incidence of CMV activation at 14 weeks after allo-HSCT was 0.11 (95% CI, 0.06–0.21) and 0.07 (only 1 study included), respectively, in retrospective and prospective studies. The incidence of CMV activation at 100 and 200 days after HSCT was 0.23 (95% CI, 0.16–0.33) and 0.49 (95% CI, 0.32–0.67), respectively. The incidence of CMV disease at 14 weeks and at 6 months after HSCT was 0.01 (95% CI, 0.01–0.02) and 0.03 (95% CI, 0.01–0.09), respectively. Thus, our systemic review and meta-analysis suggested that letermovir prophylaxis was safe and effective for CMV activation after allo-HSCT.

Amyloid light chain (AL) amyloidosis is a rare plasma cell dyscrasia with dismal prognosis. This study aims to investigate the T-cell immune checkpoint expression patterns in systemic AL amyloidosis and its relationship with clinicobiological traits. We examined the frequencies of V-domain immunoglobulin suppressor of T cell activation⁺ (VISTA⁺), programmed cell death 1⁺ (PD-1⁺), T cell immunoglobulin and mucin-domain-containing-3⁺ (Tim-3⁺), T cell immunoreceptor with Ig and ITIM domains⁺ (TIGIT⁺) T cells in peripheral blood (PB) and bone marrow (BM) from 19 patients with newly diagnosed AL amyloidosis. Patients with AL amyloidosis had significantly higher percentages of VISTA⁺ and PD-1 ⁺ T cells in PB than healthy individuals (HIs), with no statistical differences in BM. The percentages of some double-positive T cells in PB were also considerably higher in AL amyloidosis than those in HIs. Additionally, the patients with renal involvement had more PD-1⁺ and TIGIT⁺ T cells than the patients without, and PD-1⁺CD3⁺%, PD-1⁺CD4⁺%, PD-1⁺Treg% were positively correlated with 24-hour proteinuria levels. Furthermore, the AL amyloidosis patients had higher counts of PD-1⁺ Treg in PB than multiple myeloma (MM) patients, while the MM patients had higher counts of TIGIT⁺ T cells than AL amyloidosis patients. Collectively, this is the first report of elevated proportions of VISTA⁺ and PD-1⁺ T cells in PB of AL amyloidosis patients, indicating an immunosuppressive milieu, and the increased PD-1⁺ and TIGIT⁺ T cells were associated with renal damage. VISTA, PD-1, and TIGIT may be potential targets for reversing T-cell exhaustion in AL amyloidosis.

Waldenstrom macroglobulinemia (WM) is a type of incurable, indolent B-cell lymphoma that is prone to relapse. Over time, treatment strategies have progressed from cytotoxic drugs to rituximab (R)- or bortezomib (V)-based regimens, and have now entered into an era of Bruton tyrosine kinase inhibitor (BTKi)-based regimens. However, the optimal treatment for the relapsed patients is still unclear. Herein, we analyzed the outcomes of the first- and second-line therapies in 377 patients with WM to illustrate the optimal choices for second-line therapy. After a median follow-up of 45.4 months, 89 patients received second-line therapy, and 53 patients were evaluated for response. The major response rates (MRR) of first- and second-line treatment were 65.1% and 67.9% (P = 0.678). The median progression-free survival (PFS) for the second-line therapy (PFS2) was shorter than that for the first-line therapy (PFS1) (56.3 vs 40.7 months, P = 0.03). However, PFS2 in targeted drugs group (R-/V-/BTKi-based regimens) was comparable to PFS1 (60.7 months vs 44.7 months, respectively, P = 0.21). Regarding second-line therapy, patients who underwent sequential treatment escalation—such as transitioning from cytotoxic drugs to R-/V-/BTKi-based regimens or from R-/V-based to BTKi-based regimens (escalation group) —had higher MRR (80.6% vs 47.1%, respectively, P = 0.023) and longer PFS2 (50.4 vs 23.5 months, respectively, P < 0.001) compared to the non-escalation group. Patients in the escalation group also had longer post-relapse overall survival compared with the non-escalation group (median, 50.4 vs 23.5 months, respectively, P = 0.039). Our findings indicate that sequential treatment escalation may improve the survival of patients with WM.

Numerous studies have discussed the therapeutic outcomes of using cell therapy or acupuncture to treat peripheral artery disease (PAD). However, there are no long-term studies on the safety and efficacy of transplanting peripheral blood mononuclear cells (PBMNCs) via acupoints to treat PAD. We first reviewed the short-term and long-term clinical results of PAD patients treated with PBMNCs through intramuscular non-acupoint transplantation (control group; n = 45) or intramuscular acupoint transplantation (acupoint group; n = 45) at a single university hospital general medical center between December 2002 and September 2022. Pain intensity (assessed with the verbal rating scale [VRS] score) in the acupoint group was considerably lower than that in the control group at month 1 (mean ± standard deviation [SD]: 1.29 ± 0.96 vs 1.76 ± 0.82; P = 0.016) and month 3 (mean ± SD: 1.27 ± 0.90 vs 1.61 ± 0.86; P = 0.042). We observed significant improvement of VRS score (P < .001 for all) and ankle-brachial index (ABI; P < .001 for all) from baseline in both groups at months 1, 3, 6, 12, 36, and 60. The 10-year cumulative rate of major amputation–free survival (MAFS) was higher in the acupoint group as compared to the control group (81.9%, 95% confidence interval [CI]: 71.3%-94.1% vs 78.5%, 95% CI: 66.7%–92.3%; P = 0.768). Compared with the routine injection method, intramuscular transplantation of PBMNCs via selected acupoints could significantly decrease the short-term pain intensity in patients with PAD, which remains an option for consideration.

Understanding hematopoietic stem cell (HSC) heterogeneity is crucial for treating malignant blood disorders. Compared with mice, we have limited knowledge of the heterogeneity of human HSCs. Fortunately, non-human primates (NHPs) have become the best animal models for studying human HSCs. Here, we employed a public dataset derived from NHP autologous bone marrow transplantation, and focused on a total of 820 HSC clones with reconstitution capacity of all available five lineages (granulocyte, monocyte, B cell, T cell, and natural killer cell) at two time points (11/12 and/or 42/43 months). Intriguingly, unsupervised clustering on these clones revealed six HSC subtypes, including a lymphoid/myeloid balanced (LM-balanced) subtype and five single-lineage–biased subtypes. We also observed that the subtypes of these HSC clones might change over time, and a given subtype could transition into any one of the other five subtypes, albeit with a certain degree of selectivity. Particularly, each of the six subtypes was more likely to turn into lymphoid-biased rather than myeloid-biased ones. Additionally, our five-lineage classification method exhibited strong correlation with traditional lymphoid/myeloid bias classification method. Specifically, our granulocyte- and monocyte-biased subtypes were predominantly attributed to α-HSCs, while LM-balanced, B cell-biased, and T cell-biased subtypes were primarily associated with β-HSCs. The γ-HSCs were composed of a small subset of B cell-biased and T cell-biased subtypes. In summary, our five-lineage classification identifies more finely tuned HSC subtypes based on lineage output bias. These findings enrich our understanding of HSC heterogeneity in NHPs and provide important insights for human research.

爱泼斯坦-巴尔病毒（EBV）能够感染T和/或自然杀伤（NK）细胞，并在极少数情况下触发持续性EBV复制和难治性EBV相关T/NK淋巴增生性疾病（EBV-T/NK-LPDs），^1,2尤其是当扁桃体NK细胞的功能³和CD8⁺T细胞^4,5都受损了。肿瘤坏死因子样受体(TNFR)是与免疫细胞生理学密切相关的超家族的一部分。突变TNFRSF13B（编码跨膜激活因子和亲环蛋白相互作用因子[TACI]蛋白）先前被报道与常见可变免疫缺陷(CVID)相关，⁶表明TACI缺乏引起的免疫系统复杂失衡。越来越多的证据也表明TACI在T细胞反应中的潜在作用。^7,8在这里，我们报告了一系列新的杂合子TNFRSF13B6例诊断为EBV-T/NK-LPDs患者的突变。在这项工作中，我们试图扩大在EBV相关增殖性疾病患者中筛选的常规基因组，并提供一种新的可能方法来关联遗传易感性、持续性EBV感染和EBV-T/NK-LPDs病因病理学。

嵌合抗原受体T（CAR T）细胞疗法在复发或难治性B细胞急性淋巴细胞白血病（r/r B-ALL）患者中获得了令人印象深刻的缓解率；然而，高复发率仍然是一个迫切需要解决的重大挑战。¹Jing Pan博士和她在中国北京和天津的合作者一直在努力提供见解。他们最近的论文发表在柳叶刀肿瘤学2023年10月17日²进一步阐明了这个问题。在本文中，作者介绍了序贯CD19和CD22 CAR T细胞疗法（NCT04340154）的2期临床试验结果。筛选了年龄范围为1至18岁的儿科患者(n=102)，81名参与者成功入组并接受了CD19 CAR T细胞输注，其中79人继续接受了CD22 CAR T细胞输注，中位间隔为39天。该顺序输注策略(在2次输注之间有间隔)旨在降低2种CAR T产品的协同毒性并避免首次输注后的早期复发。98%的缓解率、78%的18个月无事件生存率（EFS）和96%的18个月总生存率证明了该方法的持久性。不良事件是可控的，没有死亡归因于该治疗。