Respiratory viral infections (RVIs) are among the leading cause of morbidity and mortality in pediatric hematopoietic stem cell transplant (HCT) and solid organ transplant (SOT) recipients. Transplant recipients remain at high risk for super imposed bacterial and fungal pneumonia, chronic graft dysfunction, and graft failure as a result of RVIs. Recent multicenter retrospective studies and prospective studies utilizing contemporary molecular diagnostic techniques have better delineated the epidemiology and outcomes of RVIs in pediatric transplant recipients and have advanced the development of preventative vaccines and treatment interventions in this population. In this review, we will define the epidemiology and outcomes of RVIs in SOT and HSCT recipients, describe the available assays for diagnosing a suspected RVI, highlight evolving management and vaccination strategies, review the risk of donor derived RVI in SOT recipients, and discuss considerations for delaying transplantation in the presence of an RVI.

BACKGROUND: Endemic mycoses after hematopoietic stem cell transplantation (HSCT) are rarely reported. We aimed to comprehensively review the clinical presentation and outcomes of endemic mycoses in this immunocompromised population.
METHODS: Multiple databases were reviewed from inception through May 31, 2023 using endemic fungi as keywords (e.g., coccidioides, histoplasma, blastomyces, talaromyces, and paracoccidioides). Only hematopoietic transplants were included.
RESULTS: There were 16 publications on endemic mycoses after HSCT that reported nine unique cases of histoplasmosis, seven coccidioidomycosis, and two talaromycosis. No cases of paracoccidioides and blastomycoses were identified. Fifteen cases were allogeneic hematopoietic transplant recipients and three were autologous. Many were male (14/18, 77.8%) and overall median age was 50 (range 21-75) years. Among the 16 patients with coccidiodomycosis or histoplasmosis, fever, cytopenias and disseminated disease were the most common clinical presentations, with median onset of 8 or 12 months after HSCT, respectively. Likewise, the two HSCT patients with talaromycosis presented with disseminated disease at 12 and 48 months after transplantation. The vast majority were not on effective azole prophylaxis at the time of presentation, and many had recent intensification of immunosuppression. Nine of 18 patients died (50%), and all deaths occurred among patients with disseminated endemic mycoses.
CONCLUSIONS: Endemic mycoses among HSCT are uncommon. Onset was late, after discontinuation of azole prophylaxis, or was associated with intensification of immunosuppression. Disseminated disease was a common presentation, manifested by fever and cytopenias. Attributable mortality was high, and emphasizes the need for a high index of clinical suspicion so that prompt diagnosis and treatment is provided.

UNASSIGNED: Chronic lymphocytic leukemia (CLL) can transform into fast growing lymphoma for diffuse large B-cell lymphoma (DLBCL) called Richter\'s syndrome (RS), which is commonly related to an existence of large B-cells with equal or larger size than macrophage nuclei or more than twice those of normal lymphocyte. We conducted a systematic review of the existing literature to assess the clinical efficacy of auto-HCT for patients with RS.
UNASSIGNED: We searched 4 main databases; EMBASE, Google Scholar, Scopus, PubMed and Web of Science and was done on December 26, 2021. All analyses in this study were performed by Stata software and this review was reported in accordance with PRISMA 2020.
UNASSIGNED: Data was extracted from 4 articles; the total number of patients was reported to be 110. Based on the meta-analysis findings, pooled overall survival rate was 56.36% (95%CI= (46.98-65.31). In figure 2, the forest plot of combined results is shown.
UNASSIGNED: Despite the use of common treatment regimens such as chemo immunotherapy and the availability of novel therapies including B-cell receptor inhibitors and rituximab-cyclophosphamide-hydroxydaunorubicin-Oncovin-prednisone (CHOP-R) regimen, the status of disease progression and recovery in RS cases is still not strong enough.

A 46-year-old man with myelodysplastic syndrome/myeloproliferative neoplasm-unclassifiable underwent myeloablative bone marrow transplantation from an HLA-DR-1-antigen-mismatched related donor while receiving tacrolimus and mycophenolate mofetil (MMF) for graft-versus-host disease (GVHD) prophylaxis. However, grade III acute GVHD of the gut occurred on day 20 and was treated with prednisolone (PSL) and oral beclomethasone dipropionate while continuing MMF. Subsequently, he presented with progressive epigastric pain. Endoscopy demonstrated multiple stomach and duodenal deep ulcers. The ulcers were suspected to be GVHD; thus, the PSL dose was increased and infliximab was administered; however, the ulcers exacerbated, resulting in repeated perforations and hemorrhagic shock. Furthemore, MMF was suspected as the cause of refractory ulcers and was discontinued on day 156, which resolved the ulcers after 6 months. MMF-induced gastrointestinal (GI) injury resembles anti-inflammatory drug-related ulcers and upper and lower GI tract GVHD, respectively. MMF-induced GI injury has been reportedly resolved after discontinuing or reducing the MMF dose. Several reports suggested that refractory upper GI ulcers and rectal sparing colitis were associated with MMF toxicities rather than GVHD in hematopoietic stem cell transplantations. Physicians should be aware that MMF can induce severe GI injury.

Vaccination against SARS-COV-2 is considered the most promising approach to curbing the pandemic. Patients with an immunocompromised state, such as those with hematological malignancies and organ transplantation recipients, are considered more susceptible to infection, but these at-risk patients were underrepresented in early clinical trials for vaccination. Although a growing body of studies suggests that the humoral response to COVID-19 vaccination in each of these at-risk groups of patients may be suboptimal in comparison to healthy controls, a clinical and strategic information for the further comparative analysis among these groups is not fully described. The humoral responses after two doses of BNT162b2 vaccination were evaluated in a total of 187 patients either with allogeneic hematopoietic transplantation, with renal transplantation, with anti-CD20 antibody therapy, or with anti-CD38 antibody therapy, and in 66 healthy controls. The early response at one to three months after vaccination was significantly inferior among patients with renal transplantation, patients with anti-CD20 antibody therapy, and patients with anti-CD38 antibody therapy in comparison to healthy control. But the patients with allogeneic hematopoietic transplantation showed early humoral response comparable to healthy control. The late response at 6 months after vaccination was still suboptimal among patients with renal transplantation and patients with anti-CD20 therapy. Among our patient group, renal transplant recipients had the lowest antibody titers after vaccination regardless of timing of vaccination. Patients who had received allogeneic hematopoietic transplantation attained a comparable serological response to the control group especially if they are vaccinated >300 days after transplantation, but the response was suboptimal if the vaccination was within 300 days after transplantation. Our results may provide policy makers with critical information for the further stratification of at-risk groups, helping contribute to a better allocation of resources, including additional booster vaccination.

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BACKGROUND: Defibrotide is approved in European Union for the treatment of severe sinusoidal obstruction syndrome (SOS) after HSCT. However, it has also been used for SOS prophylaxis, moderate SOS and in other complications such as transplant-associated thrombotic microangiopathy (TAM). The objective of this study was to evaluate current uses, effectiveness and safety of defibrotide in patients with HSCT.
METHODS: This multicenter, retrospective study included patients treated with defibrotide for any indication at 28 HSCT centers of the Grupo Español de Trasplante Hematopoyetico (GETH) including the pediatric subgroup Grupo Español de Trasplante de Medula en Niños (GETMON).
RESULTS: Three hundred and eighty eight patients treated with defibrotide between January 2011 and December 2018 were included. 253 patients were children, and 135 patients were adults. In total, 332 transplants were allogeneic, and the remainder were autologous. Main indications for defibrotide use were severe/very severe SOS in 173 patients, SOS prophylaxis in 135 patients, moderate SOS in 41 patients, TAM in six patients and suspected SOS in 33 patients. Overall survival (OS) at day +100 in the SOS prophylaxis group was 89% (95% CI, 87%-91%). In the group of patients with moderate and severe/very severe SOS, the OS at day +100 was 80% (95% CI, 74%-86%) and 62% (95% CI, 59%-65%), respectively (P = .0015). With a longer follow-up, median of 2 years (4 months-7 years), OS was 63% (95% CI, 59%-67%) in the SOS prophylaxis patients. OS for patients with moderate and severe/very severe SOS groups was 53% (95% CI, 47%-61%) and 26% (95% CI, 22%-30%), respectively (P = .006). 191 patients died, and SOS was the main cause of death in 23 patients (12%).
CONCLUSIONS: Defibrotide has an acceptable safety profile with an improved response in severe/very severe SOS compared with historical controls, mainly in pediatric patients. Use of defibrotide for prophylaxis may improve prognosis of patients at high risk of complications due to endothelial damage such as those who receive a second transplant. SOS has an important impact on the HSCT long-term survival, as can be concluded from our study.

Objective: To analyze family-based haplotype frequencies of HLA-A, -B, -C, -DRB1 and -DQB1 genes and their clinical significance. Methods: The data of HLA genotyping in 3568 families undergoing related haploidentical transplantation between 2012 and 2017 at the First Affiliated Hospital of Soochow University were retrospectively evaluated. The HLA genotyping was performed by PCR amplification with sequence-based typing (PCR-SBT) and sequence-specific oligonucleotide probe (PCR-SSOP) methods. The family genetic analysis and haplotype frequencies were also investigated. Results: All the families were divided into 3 groups, including group1 of 1 422 entire families; group2 of 1 310 patients and either of their parents or one of their children; group3 of 836 patients and their HLA≥5/10 matched sibling donors. In the haplotypes with frequencies greater than 0.1% in group1+ group2, the frequency of A*11∶01-B*40∶01-C*03∶04-DRB1*11∶01-DQB1*03∶01, A*02∶07-B*51∶01-C*14∶02-DRB1*09:01-DQB1*03∶03 were significantly different between group1 and group2 (P=0.029, 0.033) . The frequency of A*11∶01-B*46∶01-C*01∶02∶01G-DRB1*09∶01-DQB1*03∶03 was significantly different between group1 and group3 (P=0.035) . The frequency of A*02∶01-B*40∶01-C*07∶02-DRB1*09∶01-DQB1*03∶03 was significantly different between group1 and group2 (P=0.034) , or group1 and group3 (P=0.034) . The frequency of A*24∶02-B*13∶01-C*03∶04-DRB1*12∶02-DQB1*03:01 was significantly different between group2 and group3 (P=0.046) . Conclusion: In this study, we summarize the prevalence of haplotype frequencies in terms of HLA-A, -B, -C, -DRB1 and-DQB1. Based on the database of family haplotype analysis, patients and donor candidates are sorted with matched HLA genotype while unmatched HLA haplotype. Even in patients without entire family information, HLA haplotype analysis assists in choosing the optimal related or unrelated donors.
目的： 研究单倍型移植中HLA-A、-B、-C、-DRB1、-DQB1单倍型频率，并探讨其临床意义。 方法： 回顾性分析2012-2017年在苏州大学附属第一医院拟行亲缘HLA单倍型移植的3 568个家系，同时采用基因测序（PCR-SBT）和寡核苷酸探针杂交（PCR-SSOP）进行HLA基因分型检测，并进行家系单倍型分析。 结果： 全部3 568个家系可分为3种情况：组1为1 422个完整家系，组2为1 310个仅有患者与一个亲代或子代的家系，组3为836个仅有患者与一个HLA≥5/10基因型相同同胞的不完整家系。组1和组2合并统计后建立单倍型总频率表。总频率≥0.1%的单倍型中：A*11∶01-B*40∶01-C*03∶04-DRB1*11∶01-DQB1*03∶01、A*02∶07-B*51∶01-C*14∶02-DRB1*09∶01-DQB1*03∶03的单倍型频率在组1和组2间差异有统计学意义（P值分别为0.029、0.033）；A*11∶01-B*46∶01-C*01∶02∶01G-DRB1*09∶01-DQB1*03∶03的频率在组1和组3间差异有统计学意义（P=0.035）；A*02∶01-B*40∶01-C*07∶02-DRB1*09∶01-DQB1*03∶03的频率在组1和组2、组1和组3间差异均有统计学意义（P值分别为0.034、0.034）；A*24∶02-B*13∶01-C*03∶04-DRB1*12∶02-DQB1*03∶01的频率在组2和组3间差异有统计学意义（P=0.046）。 结论： 本研究建立了HLA-A、-B、-C、-DRB1、-DQB1单倍型频率总表，同时列举完整家系单倍型研究中分析基因型相同但单倍型完全不合，却被拟作为潜在供者移植的临床病例。家系不完整的供受者可通过本表进行单倍型分析，结合家系中其他成员HLA分型检测结果，为选择最佳供者及检索非血缘供者提供参考。.

Bone marrow transplantation is a treatment for various cancers and genetic diseases, and the only case of a cured HIV infection involved the use of this clinical procedure, highlighting the potential use of this therapy for curing many chronic diseases. However, little is known about how chronic viral infection influences lymphocyte reconstitution after bone marrow transplantation. To address this, we infected mice with chronic lymphocytic choriomeningitis virus, and performed bone marrow transplantation to assess lymphocyte reconstitution. Interestingly, we observed that adoptively transferred marrow cells exhibited preferential B cell differentiation in chronically infected mice. Moreover, donor marrow cells that were adoptively transferred into chronically infected mice differentiated into virus-specific CD8 T cells that were able to expand after PD-L1 blockade. Taken together, our data show that chronic viral infection induces a biased differentiation of bone marrow stem cells into B cells, and that exhausted virus-specific CD8 T cells generated de novo in this setting are rescuable by PD-1 blockade. These data contribute to the understanding of how chronic viral infection impacts lymphocyte reconstitution, and may provide valuable information to improve current hematopoietic transplantation regimens in chronically infected hosts.

Relapse is the most frequent cause of treatment failure after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Natural killer (NK) cells and γδ T cells reconstitute early after allo-HSCT, contribute to tumor immunosurveillance via major histocompatibility complex-independent mechanisms and do not induce graft-versus-host disease. Here we performed a quantitative and qualitative analysis of the NK and γδ T cell repertoire in healthy individuals, recipients of HLA-matched sibling or unrelated donor allo-HSCT (MSD/MUD-HSCT) and umbilical cord blood-HSCT (UCB-HSCT). NK cells are present at high frequencies in all allo-HSCT recipients. Immune reconstitution (IR) of vδ2+ cells depended on stem cell source. In MSD/MUD-HSCT recipients, vδ2+ comprise up to 8% of the total lymphocyte pool, whereas vδ2+ T cells are barely detectable in UCB-HSCT recipients. Vδ1+ IR was driven by CMV reactivation and was comparable between MSD/MUD-HSCT and UCB-HSCT. Strategies to augment NK cell mediated tumor responses, similar to IL-15 and antibodies, also induced vδ2+ T cell responses against a variety of different tumor targets. Vδ1+ γδ T cells were induced less by these same stimuli. We also identified elevated expression of the checkpoint inhibitory molecule TIGIT (T cell Ig and ITIM domain), which is also observed on tumor-infiltrating lymphocytes and epidermal γδ T cells. Collectively, these data show multiple strategies that can result in a synergized NK and γδ T cell antitumor response. In the light of recent developments of low-toxicity allo-HSCT platforms, these interventions may contribute to the prevention of early relapse.