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1.
The indirect effects of CMV reactivation on patients following allogeneic hematopoietic stem cell transplantation: an evidence mapping
Wu, X., Ma, X., Song, T., Liu, J., Sun, Y., Wu, D.
Annals of hematology. 2024
Abstract
Cytomegalovirus (CMV) reactivation following allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a challenging problem, and the impact on the risk of overall mortality (OM) and non-relapse mortality (NRM) in patients following allo-HSCT is still controversial. Utilizing the evidence mapping method, we aimed to assess the effect of CMV infection on outcomes of patients post-transplantation and identify research gaps through systematic reviews (SRs) and clinical studies. PubMed, EMBASE, Web of Science, and Cochrane library databases were searched from inception until 5 July 2022 to identify relevant literature. After systematic literature screening and data extraction, evidence mapping of the effects of CMV reactivation on patients post-allo-HSCT was conducted. Three SRs and 22 clinical studies were included. In one SR, CMV reactivation was associated with an increased risk of mortality (HR 1.46; 95% CI, 1.24-1.72; P ≤ 0.001). In two SRs, CMV reactivation was associated with NRM. One SR reported CMV reactivation was potentially associated with significant protection against relapse in patients with acute myelocytic leukemia (AML), but no significant correlation with graft-versus-host disease (GVHD) was found. Lastly, in one SR CMV reactivation significantly increased the risk of invasive fungal disease (IFD). Most clinical articles reported that CMV reactivation increased the risk of renal dysfunction, poor graft function, re-hospitalization, and bacterial infections. CMV reactivation following allo-HSCT is associated with an increased risk of OM, NRM, IFD, and renal dysfunction, as well as a reduced risk of relapse in patients with AML.
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2.
The clinical value of anal swabs for microbial detection in allogeneic haematopoietic stem cell transplantation
Gao, J., Lin, D., Hou, C., Shen, Y., Li, Y., Wu, D., Xu, Y.
Transplantation and cellular therapy. 2023
Abstract
BACKGROUND The intestinal microbiota plays critical roles in allogeneic haematopoietic stem cell transplantation (allo-HSCT). Rapid and effective microbial detection methods have important guiding value for the selection of intervention strategies for transplant patients. We evaluate the application of anal swab test before transplantation in allo-HSCT patients. STUDY DESIGN A total of 120 allo-HSCT patients who underwent anal swab testing before allo-HSCT were retrospectively analysed and divided into sterile (aseptic growth-negative), G+ (gram-positive bacterial colonization) and G- (gram-negative bacterial colonization) groups. RESULTS 16S rRNA sequencing showed that gram-negative bacteria predominated in the G- group before and after transplantation. Compared with the sterile group, NK cell percentage was higher and T cell percentage was lower after transplantation in the G- group at one month after transplantation. The percentage of CD4+T and CD4+CD8+ T cells was lower, and the percentage of Treg was higher in the G- group. The plasma levels of pro-inflammatory cytokines (TNF-α, IFN-γ, IL-6, and IL-17A) were lower in the G- group at 2 weeks after transplantation than in the sterile group. The cumulative incidence of grade III-IV aGVHD was lower in the G- group than in the sterile group. Gram-negative bacterial colonization before allo-HSCT was associated with low rates of BSI within 100 days posttransplatation, and CMV reactivation after 100 days to 2 years posttransplatation. Moreover, patients in the G- group had a higher rate of 2-year GRFS compared with patients in the sterile group. CONCLUSIONS The detection results using anal swabs were consistent with the gram-negative or positive bacteria abundance of 16S rRNA sequencing results and associated with immune homeostasis and clinical outcomes after allo-HSCT. Anal swab testing may have potential advantages as a simple and effective method for microbial detection in allo-HSCT.
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3.
The impact of pre-transplant anti-HLA antibodies in transplants from HLA-identical sibling donors: A multicenter study
Wei, X., Chang, Y., Zhu, X., Hu, X., Guo, R., Zhang, Y., Ma, X., Han, Y., Wang, Y., Qiu, H., et al
Hla. 2023
Abstract
Few studies have performed comparative analysis of the outcome of hematopoietic stem cell transplantation from HLA-identical sibling donors (ISD-HSCT) in patients with or without anti-HLA Abs. In this study we retrospectively collected data from a multicenter study to analyze the distribution and impact of the pre-existing anti-HLA Abs in ISD-HSCT. Among 402 recipients, 111 were positive for anti-HLA Abs. Gender, time from diagnosis to transplantation and distribution of primary disease might be risk factors for the occurrence of anti-HLA Abs. We found that patients with anti-HLA Abs had delayed neutrophil engraftment and were more vulnerable to experience Cytomegalovirus (CMV) reactivation. The presence of anti-HLA Abs was proved to be an independent risk factor for neutrophil engraftment (HR 1.42 95% CI 1.13-1.80, p = 0.003) and CMV reactivation (HR 2.03 95% CI 1.19-3.46, p = 0.009). We found that anti-HLA Abs have a negative impact on the prognosis in the early period after transplantation from sibling donors and anti-HLA Abs was also an independent risk factor for the overall survival (OS) at 180 days (HR 2.32, 95% CI 1.03-5.27, p = 0.042) among female recipients. In conclusion, anti-HLA Abs have a negative impact on the prognosis early after ISD-HSCT.
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4.
Graft-versus-host disease and relapse/rejection-free survival after allogeneic transplantation for idiopathic severe aplastic anemia: a comprehensive analysis from the SAAWP of the EBMT
Devillier, R., Eikema, D. J., Dufour, C., Aljurf, M., Wu, D., Maschan, A., Kulagin, A., Halkes, C. J. M., Collin, M., Snowden, J., et al
Haematologica. 2023
Abstract
Survival after Allo-HSCT for severe idiopathic aplastic anemia (SAA) has improved in recent years, approaching 75% at 5 years. However, an SAA-adapted composite endpoint, GVHD and relapse/rejection-free survival (GRFS), may more accurately assess patient outcomes beyond survival. We analyzed GRFS to identify risk factors and specific causes of GRFS failure. Our retrospective analysis from the SAAWP of the EBMT included 479 patients with idiopathic SAA who underwent Allo-HSCT in 2 conventional situations: i) upfront Allo-HSCT from a matched related donor (MRD) (upfront cohort), and ii) Allo-HSCT for relapsed or refractory SAA (rel/ref cohort). Relevant events for GRFS calculation included graft failure, grade 3-4 acute GVHD, extensive chronic GVHD, and death. In the upfront cohort (n=209), 5-year GRFS was 77%. Late Allo-HSCT (i.e., >6 months after SAA diagnosis) was the main poor prognostic factor, specifically increasing the risk of death as the cause of GRFS failure (HR: 4.08, 95% CI [1.41-11.83], p=0.010). In the rel/ref cohort (n=270), 5-year GRFS was 61%. Age was the main factor significantly increasing the risk of death (HR: 1.04, 95% CI [1.02-1.06], p.
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5.
Adenovirus infection diagnosed by metagenomic next-generation sequencing after haploidentical hematopoietic stem cell transplantation: A multicenter study in China
Wu, Q., Wu, Y., Zhao, Y., Zhang, Y., Cao, J., Wu, D., Zhou, J., Chen, F.
Transplant infectious disease : an official journal of the Transplantation Society. 2023;:e14054
Abstract
OBJECTIVE This study aims to observe and analyze the clinical characteristics and prognosis of adenovirus (ADV) infection diagnosed by metagenomic next-generation sequencing (mNGS) after haploidentical hematopoietic stem cell transplantation (Haplo-HSCT), which was performed following Beijing Protocol. METHODS The clinical data of patients who developed ADV infection diagnosed by mNGS after Haplo-HSCT between January 2019 and March 2021, recorded in three transplantation centers, were retrospectively analyzed. Potential risk factors for infection and the clinical manifestations of ADV involvement in different end-organs were also studied. Additionally, the patient prognosis regarding the available treatment was observed. RESULTS A total of seven patients were diagnosed with ADV infection by the mNGS technique after Haplo-HSCT of 976 patients enrolled. The risk factors for infection included antithymocyte globulin steroid-refractory graft-versus-host disease (GVHD) history, CD25 monoclonal antibody or ruxolitinib treatment history and <300 cells/μL of CD3+ T cells count in peripheral blood. The clinical manifestations of ADV infection included encephalitis, hepatitis, cystitis, and pneumonia. Six patients were treated with cidofovir (CDV) and intravenous immunoglobulin (IVIg), and one with CDV, ribavirin, IVIg, thymosin Alpha-1 for injection and low-dose donor lymphocyte infusion. One case showed negative ADV DNA results with improved conditions; however, the patient died of the relapse of the primary disease in the later stage. The remaining six died of ADV infection. CONCLUSION mNGS can provide screening for ADV and information on ADV subtypes, helpful to understand tissue tropism. This technique could be useful in diagnosing patients at high risk for ADV infection. ADV infection can involve multiple organs, has difficulty in early diagnosis, and has a poor prognosis. Currently, effective treatments are inadequate.
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6.
Prognostic significance of persisting DNMT3A, ASXL1, and TET2 mutation burden in acute myeloid leukemia patients with allogeneic hematopoietic stem cell transplantation during complete remission
Lai, X., Xiao, J., Wang, T., Hou, C., Chen, J., Wu, D., Xu, Y.
Leukemia & lymphoma. 2023;:1-9
Abstract
We retrospectively analyzed 155 AML patients with DAT mutations at diagnosis who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) at complete remission. Of the 155 AML patients with DAT mutations at diagnosis, 59 (38.1%) patients had persisting DAT mutations pretransplantation. Compared to patients with pretransplant DAT transitions, patients with persisting DAT mutation burden were shown to be older (p = 0.004), and fewer patients had TET2 mutations at diagnosis (p = 0.033). Patients with persistent DAT mutation burden had shorter overall survival (OS) (3-year OS: 59.3% vs. 83.0%, p < 0.001) and disease-free survival (DFS) (3-year DFS: 56.1% vs. 83.0%, p < 0.001) with a higher cumulative incidence of relapse (CIR) (24.6% vs. 17.4%, p = 0.002) than those with DAT transitions. Additionally, multivariate analysis confirmed that persisting DAT mutations were an independent adverse factor for relapse, OS, and DFS. Collectively, persisting DAT mutations prior to allo-HSCT at complete remission for AML correlated with negative outcomes.
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7.
Similar outcomes following non-first-degree and first-degree related donor haploidentical hematopoietic cell transplantation for acute leukemia patients in complete remission: a study from the Global Committee and the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation
Ye, Y., Labopin, M., Chen, J., Gulbas, Z., Zhang, X., Koc, Y., Blaise, D., Ciceri, F., Polge, E., Houhou, M., et al
Journal of Hematology & Oncology. 2023;16(1):25
Abstract
There are situations where non-first-degree (NFD) related donors have to be considered as alternatives to first-degree (FD) related donors for haploidentical hematopoietic cell transplantation (HAPLO). However, the efficacy of these NFD related transplants remains uncertain. All consecutive adult patients (≥ 18 years) with acute myelogenous leukemia (AML) or acute lymphocytic leukemia (ALL) in CR who underwent a first HAPLO between 2010 and 2021 in the European Society for Blood and Marrow Transplantation (EBMT) registry were analyzed. Exact matching and propensity score matching was used. The NFD-to-FD ratio was 1:3. 2703 patients (AML: n = 2047; ALL: n = 656) in CR received a first HAPLO from either NFD (n = 154) or FD (n = 2549) related donors in 177 EBMT centers. 123 NFD and 324 FD HAPLO were included for analysis after matching. Median patient age was 35.6 and 37.2 for the NFD and FD cohorts, respectively. Both cohorts reached good engraftment rates (NFD: 95.7% vs. FD, 95.6%; p = 0.78). The 2-year relapse incidence (NFD, 21.1% vs. FD, 22.6%; p = 0.84) and non-relapse mortality (NRM) (NFD, 13.2% vs. FD, 17.7%; p = 0.33) were not significantly different. The 2-year overall survival (OS) (NFD, 71.8% vs. FD, 68.3%; p = 0.56), leukemia-free survival (LFS) (NFD, 65.7% vs. FD, 59.7%; p = 0.6) and graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS) (NFD, 50.9% vs. FD, 47.8%; p = 0.69) also showed no significant differences. The two cohorts showed no difference in terms of cumulative day 180 grade II-IV, grade III-IV acute GVHD, 2-year cumulative incidences of chronic and extensive chronic GVHD. For HAPLO in patients with acute leukemia, NFD related donors could be equivalent substitutions when FD related donors are not available.
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8.
The efficacy of first salvage therapy determines the outcomes of adult patients with type 1 primary refractory acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation
Yu, Z., Yao, Y., Zhang, Y., Chen, J., Xu, Y., Xue, S., Qiu, H., Tang, X., Han, Y., Chen, S., et al
Annals of hematology. 2023
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9.
Assessment of risk factors for acute graft-versus-host disease post-hematopoietic stem cell transplantation: a retrospective study based on a proportional odds model using a nonlinear mixed-effects model
Xue, L., Song, L., Yu, X., Yang, X., Xia, F., Ding, X., Huang, C., Wu, D., Miao, L.
Therapeutic advances in hematology. 2023;14:20406207231205406
Abstract
BACKGROUND Acute graft-versus-host disease (aGVHD) is a major complication following hematopoietic stem cell transplantation (HSCT). OBJECTIVE This study aimed to explore the risk factors for the incidence of aGVHD in patients post-HSCT. DESIGN This was a retrospective study. METHODS A total of 407 patients were enrolled. The patients' data were recorded from the medical records. The exposure of cyclosporine was estimated based on a population pharmacokinetics model. The occurrence of aGVHD was clinically graded and staged in severity from grades I to IV. A proportional odds model that estimated the cumulative probabilities of aGVHD was used to analyze the data using a nonlinear mixed-effects model. Then, the model parameters and plausibility were evaluated by bootstrap and visual predictive checks. RESULTS The typical probabilities were 18.9% and 17.9% for grade II and grades III-IV, respectively. The incidence of grade II and grade III-IV aGVHD for human leukocyte antigen (HLA) haplo sibling donor patients was higher than that for HLA-matched donor patients. The incidence of grade II and grade III-IV aGVHD decreased with increasing early cyclosporine trough concentration; however, cyclosporine exposure was not associated with the incidence of aGVHD. CONCLUSION HLA matching and early cyclosporine trough concentration were important factors for the occurrence of aGVHD.
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10.
Upregulation of HIF-1α contributes to complement activation in transplantation-associated thrombotic microangiopathy
Qi, J., Pan, T., You, T., Tang, Y., Chu, T., Chen, J., Fan, Y., Hu, S., Yang, F., Ruan, C., et al
British journal of haematology. 2022
Abstract
Transplantation-associated thrombotic microangiopathy (TA-TMA) is a severe complication of haematopoietic stem cell transplantation (HSCT). Complement activation is involved in the development of TA-TMA. However, the underlying mechanism is unclear. Therefore, 21 samples of TA-TMA and 1:1 matched controls were measured for hypoxia-inducible factor-1α (HIF-1α) and complement protein. The mechanism was investigated both in vitro and in vivo. In this study, we found that levels of HIF-1α were significantly higher in TA-TMA patients than that in non-TA-TMA controls. Upregulation of HIF-1α induced an increase in membrane-bound complement C3 and dysfunction of human umbilical vein endothelial cells (HUVECs) in vitro. Increasing HIF-1α in vivo led to C3 and C5b-9 deposition in the glomerular endothelial capillary complex, thrombocytopenia, anaemia, and increased serum lactate dehydrogenase (LDH) levels in wild-type (WT) but not in C3(-/-) mice subjected to HSCT. High platelet aggregation in peripheral blood and CD41-positive microthrombi in the kidney were also found in dimethyloxallyl glycine (DMOG)-treated mice, recapitulating the TA-TMA phenotype seen in patients. Comprehensive analysis, including DNA array, luciferase reporter assay, chromatin immunoprecipitation (ChIP)-seq, and quantitative polymerase chain reaction (PCR), revealed that HIF-1α interacted with the promoter of complement factor H (CFH) to inhibit its transcription. Decreased CFH led to complement activation in endothelial cells.