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1.
Molecular Biomarkers in Ocular Graft-versus-Host Disease: A Systematic Review
Bohlen, J., Gomez, C., Zhou, J., Martinez Guasch, F., Wandvik, C., Sunshine, S. B.
Biomolecules. 2024;14(1)
Abstract
Ocular graft-versus-host disease (oGVHD) affects ~50% of post-stem cell transplant patients and is the only form of GVHD diagnosed without a biopsy. As it must be distinguished from other dry eye diseases, there is a need to identify oGVHD biomarkers to improve diagnosis and treatment. We conducted a systematic review of 19 scholarly articles published from 2018 to 2023 including articles focused on adult patients diagnosed with oGVHD following allogeneic hematopoietic stem cell transplant and used biomarkers as the outcome measure. Articles that were not original investigations or were not published in English were excluded. These clinical investigations explored different molecular oGVHD biomarkers and were identified on 3 October 2023 from the Scopus, PubMed, and Embase databases by using search terms including ocular graft-versus-host disease, biomarkers, cytokines, proteomics, genomics, immune response, imaging techniques, and dry-eye-related key terms. The Newcastle-Ottawa scale for case-control studies was used to assess bias. From the 19 articles included, cytokine, proteomic, lipid, and leukocyte profiles were studied in tear film, as well as ocular surface microbiota and fluorescein staining. Our findings suggest that cytokine profiling is the most studied oGVHD biomarker. Additionally, variations correlating these biomarkers with disease state may lead to a more targeted diagnosis and therapeutic approach. Limitations include language bias, publication bias, and sampling bias, as well as a lack of appropriate controls for included studies.
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2.
A Systematic Review and Metasynthesis of Hematopoietic Stem Cell Transplant (HSCT) Patient's Experiences of Long-Term Monitoring Clinics from the Patient's Perspective
Bell, B., Thursby, S., Limbrick, H., Swainston, K.
Journal of patient experience. 2024;11:23743735241229378
Abstract
This study aimed to synthesize all qualitative evidence on the experiences of hematopoietic stem cell transplant (HSCT) patients attending long-term monitoring clinics from their perspective. A systematic search of the literature was undertaken across 8 databases. The Critical Appraisal Skills Program was used to evaluate each study's quality. Confidence in the Evidence from Reviews of Qualitative Research was employed to assess confidence in each finding. Three themes from 4 qualitative studies were identified relating to patients' experiences, "[It's] important to maintain a good relationship with the nurses and doctors," "There's always the thing about the logistics," and "Once you have cancer, you're always thinking do I have it again?". The findings suggest that HSCT patients' experiences of long-term follow-up care clinics are influenced by the patient-provider relationship and the logistical set-up of monitoring practices, and weakly connected with fear of cancer recurrence. Future research is needed to understand the impact of each finding of this review, specifically in relation to patients' country of residence to gain a greater understanding of their monitoring support needs.
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3.
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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4.
The Potential Role of NOD2/CARD15 Genotype as a Prognostic Indicator for Bone Marrow Transplantation Outcomes in Patients With Acute Lymphoblastic Leukemia and Acute Myeloid Leukemia: A Systematic Review
Ahmadinia, L., Rangrej, S. B., Miranda, M., Shailer, C., Ahmed, W., Carvalho, V., Rathore, R.
Cureus. 2024;16(1):e52329
Abstract
Hematopoietic stem-cell transplantation (HSCT) has emerged as a groundbreaking therapeutic option for acute myeloid leukemia (AML) and specific subtypes of acute lymphoblastic leukemia (ALL). The prognostic significance of the NOD2/CARD15 gene has been explored alongside various factors, encompassing diverse patient cohorts and gene variants. Siblings and unrelated donors used for stem cell transplantation exhibit significant associations between their genetic variations and graft-versus-host disease incidence. The transplantation of stem cells for leukemia patients involves numerous considerations, including patient survival, relapse rates, disease stage, donor and recipient ages, and compatibility. This study delved into research on the NOD2/CARD15 gene and its mutations to assess its suitability as a screening tool. A comprehensive literature search encompassing PubMed, ScienceDirect, and Google Scholar articles yielded 4,840 articles. After removing duplicates and applying inclusion and exclusion criteria, we narrowed the search results to 876 articles. Subsequent screening of abstracts and titles resulted in the selection of 230 relevant articles. Further exclusion of 198 articles unrelated to the research question led to the scrutinizing of 32 full-text articles, which were assessed against inclusion and exclusion criteria. Emphasis was placed on articles that specifically investigated the role of NOD2/CARD15 as a predictive factor for HSCT outcomes, ultimately resulting in the inclusion of 19 articles in this study. Single nucleotide polymorphisms (SNPs) such as NOD2 and CARD15 have demonstrated their potential as reliable genetic markers for predicting post-transplantation relapse and disease outcomes. Patients positive for these genetic markers have exhibited reduced overall survival and event-free survival and increased transplant-related mortality. Interventions with interferon-gamma and muramyl tripeptide phosphatidylethanolamine have been considered to mitigate the inflammatory effects of these SNPs, thus enhancing the influence of natural killer cells on abnormal cells and potentially extending patient survival. NOD2/CARD15 typing may aid in identifying patients at higher risk for relapse and improving their clinical outcomes after allogeneic stem cell transplant, particularly in ALL patients. However, no remarkable change was observed in AML patients. Additionally, this study underscores the pivotal roles of adaptive and innate immune responses and their interplay in stem cell transplant immunology.
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5.
Diagnostic and prognostic role of elafin in skin acute graft versus host disease: a systematic review
Bhattarai, A., Shah, S., Yadav, R., Dhakal, G., Neupane, R., Paudel, S., Bhandari, P., Abu Serhan, H., Sah, R., Sah, S., et al
Hematology (Amsterdam, Netherlands). 2024;29(1):2293497
Abstract
BACKGROUND AND OBJECTIVE Graft versus host disease (GVHD) is the common complication seen after allogeneic hematopoietic stem cell transplantation (HSCT) and a pleomorphic syndrome that resembles autoimmune and other immunologic disorders, leading to profound immune dysregulation and organ dysfunction. The most common targets of GVHD are skin, gastrointestinal tract and liver. GVHD is classified as acute graft versus host disease (aGvHD) if it occurs within the first 100 days after HSCT and chronic graft versus host disease(cGVHD) if it occurs after day 100. The skin is most frequently and earliest affected by aGvHD, followed by the gastrointestinal tract and liver. An ideal biomarker would predict the onset and severity of clinical acute GVHD and help to direct management, and this is an area of active research regarding the use of biomarkers for diagnosis and prognosis of acute GVHD. Recently, elafin has been identified as a potential plasma biomarker for aGVHD. METHOD We searched the databases PubMed, Cochrane library, and medRxiv for all studies investigating the Diagnostic or prognostic role of elafin in GVHD. We set the search strategy incorporating the search terms, 'elafin', 'graft versus host', and 'GVHD', and operated using the Boolean operators 'AND', and 'OR'. Thus, retrieved articles were then exported on an Excel® sheet, and duplicates were removed. The systematic review was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. After selecting the study based on inclusion criteria, data on study characteristics and biomarker description was extracted on a pre-determined data extraction table on the Microsoft Excel version. The quality assessment of the included studies was determined using the QUIPS tool. RESULT The search revealed 547 studies and 6 studies that met the eligibility criteria of this review have been included. The major finding of our study is the significant elevation of elafin in skin aGVHD. CONCLUSION Elafin is a significant biomarker for diagnosis and prognosis of skin aGVHD and should be assessed within 2 weeks of the onset of the disease.
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6.
Risk factors for BK virus-associated hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation: A systematic review and meta-analysis
Zhou, X., Zhang, S., Fan, J., Zhu, X., Hu, S.
Clinical transplantation. 2023;:e15121
Abstract
OBJECTIVE AND BACKGROUND BK virus-associated hemorrhagic cystitis (BKV-HC) is an intractable complication leading to higher mortality and prolonged hospitalization among allogeneic hematopoietic stem cell transplantation (allo-HCT) recipients. Therefore, identifying the potential risk factors of BKV-HC after allo-HCT is crucial to improve prognosis and for early prevention. However, the risk factors for BKV-HC remain debatable. Therefore, we conducted a systematic review and meta-analysis to identify the risk factors for BKV-HC, for early prevention of the occurrence of BKV-HC and to improve the quality of life and prognosis of allo-HCT recipients. METHODS We searched relevant studies from PubMed, EMBASE, and the Cochrane Library up to February 2023. The odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) of all risk factors were calculated to evaluate their effects on the occurrence of BKV-HC. RESULTS Overall, 11 studies involving 2556 allo-HCT recipients were included in this meta-analysis. All included studies were retrospective and published between 2013 and 2022. We found that male sex (OR = 1.32; 95% CI, 1.07-1.62; p = .009, I(2) = 34%), haploidentical donor (OR = 1.84; 95% CI, 1.18-2.87; p = .007, I(2) = 23%), myeloablative conditioning (OR = 1.76; 95% CI, 1.36-2.28; p < .0001, I(2) = 45%), acute graft versus host disease (aGVHD) (OR = 2.73; 95% CI, 2.02-3.69; p < .0001, I(2) = 46%), chronic graft versus host disease (cGVHD) (OR = 1.71; 95% CI, 1.12-2.60; p = .01, I(2) = 0%), and cytomegalovirus (CMV) reactivation (OR = 3.13; 95% CI, 1.12-8.78; p = .03, I(2) = 79%) were significantly associated with BKV-HC in the univariable analysis. CONCLUSIONS Our meta-analysis indicated that male sex, haploidentical donor, myeloablative conditioning, aGVHD, cGVHD, and CMV reactivation were potential risk factors for BKV-HC.
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7.
Prognostic Value of Hematogones in Patients With Hematopoietic Disorders After Allogeneic Hematopoietic Stem Cell Transplantation: A Systematic Review and Meta-Analysis
Mori, H., Koyama, D., Sato, Y., Kataoka, Y., Taito, S., Ishio, T., Teshima, T., Yokota, I.
Cureus. 2023;15(10):e47184
Abstract
This systematic review and meta-analysis aimed to determine whether hematogones in patients with hematopoietic disorders after allogeneic hematopoietic stem cell transplantation (allo-HSCT) are associated with clinical outcomes. We searched the MEDLINE, Embase, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and World Health Organization International Clinical Trials Registry Platform databases from their inception to March 2023. The primary outcome in the summary of findings was three-year relapse-free survival (RFS), and secondary outcomes in the summary of findings included three-year relapse, non-relapse mortality (NRM), overall survival (OS), acute and chronic graft-versus-host disease (GVHD), and infection. The certainty of evidence was determined using the grading of recommendation assessment, development, and evaluation approaches. A systematic review and meta-analysis of outcome measures were conducted using a random-effects model. This study protocol was registered in the Open Science Framework. A total of six studies (including 888 patients) were included in the meta-analysis. Hematogones were related to favorable three-year RFS (risk ratio (RR) = 1.84; 95% confidence interval (CI) = 1.01 to 3.34) and favorable NRM (RR = 0.14; 95% CI = 0.04 to 0.51), OS (RR = 1.51; 95% CI = 1.13 to 2.02), and acute GVHD (RR = 0.44; 95% CI = 0.33 to 0.59). The certainty of the evidence was low for RFS, NRM, OS, and acute GVHD. Evidence regarding the association between hematogones, relapse, and infections is uncertain. Hematogones may be a prognostic factor for long-term prognosis and acute adverse events in patients with hematopoietic disorders after allo-HSCT. Further studies are required to address the long-term life-threatening events.
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8.
Diagnostic yield for video capsule endoscopy in gastrointestinal graft- versus -host disease: a systematic review and metaanalysis
Varkey, J., Jonsson, V., Hessman, E., De Lange, T., Hedenström, P., Oltean, M.
Scandinavian journal of gastroenterology. 2023;:1-8
Abstract
BACKGROUND The gastrointestinal tract is the second most involved organ for graft-versus-host disease where involvement of the small intestine is present in 50% of the cases. Therefore, the use of a non-invasive investigation i.e., video capsule endoscopy (VCE) seems ideal in the diagnostic work-up, but this has never been systematically evaluated before. OBJECTIVE The aim of this systematic review was to determine the efficacy and safety of VCE, in comparison with conventional endoscopy in patients who received hematopoietic stem cell transplantation. METHOD Databases searched were PubMed, Scopus, EMBASE, and Cochrane CENTRAL. All databases were searched from their inception date until June 17, 2022. The search identified 792 publications, of which 8 studies were included in our analysis comprising of 232 unique patients. Efficacy was calculated in comparison with the golden standard i.e., histology. Risk of bias assessment was performed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. RESULTS The pooled sensitivity was higher for VCE at 0.77 (95% CI: 0.60-0.89) compared to conventional endoscopy 0.62 (95% CI: 0.47-0.75) but the difference was not statistically significant (p = 0.155, Q = 2.02). Similarly, the pooled specificity was higher for VCE at 0.68 (95% CI: 0.46-0.84) than for conventional endoscopy at 0.58 (95% CI: 0.40-0.74) but not statistically significant (p = 0.457, Q = 0.55). Moreover, concern for adverse events such as intestinal obstruction or perforation was not justified since none of the capsules were retained in the small bowel and no perforations occurred in relation to VCE. A limitation to the study is the retrospective approach seen in 50% of the studies. CONCLUSION The role of video capsule endoscopy in diagnosing or dismissing graft-versus-host disease is not yet established and requires further studies. However, the modality appears safe in this cohort.
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9.
Risk factors for bloodstream infection in paediatric Haematopoietic stem cell transplantation: A systematic review and meta-analysis
Yang, M., Xin, L., Li, H., Lu, X., Pan, X., Lei, S., Li, Y., Zhu, L., Zhu, Q., Jiang, R., et al
The Journal of hospital infection. 2023
Abstract
BACKGROUND Haematopoietic stem cell transplantation (HSCT), a standard treatment for paediatric haematological diseases, is highly associated with bloodstream infections (BSIs), which may increase mortality. AIM: This study aimed to explore the risk factors for BSI in paediatric HSCT recipients. METHODS We searched three English databases and four Chinese databases from inception to March 17, 2022. Eligible studies included randomized controlled trials, cohort studies, and case-control studies that enrolled HSCT recipients aged ≤ 18 years and reported BSI risk factors. Two reviewers independently screened studies, extracted data, and assessed the risk of bias. Using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) we assessed certainty of body of evidence. FINDINGS Fourteen studies involving 4602 persons were included. The incidences of BSI and associated mortality in paediatric HSCT recipients were approximately 10%-50% and 5%-15%, respectively. Meta-analysis of all studies revealed that previous BSI before HSCT (relative effect [RE] 2.28, 95% confidence interval [CI] 1.19-4.34, moderate certainty) and receiving an umbilical cord blood transplant (RE 1.55, 95% CI 1.22-1.97, moderate certainty) were probably associated with an increased risk of BSI. Meta-analysis of studies with low risk of bias reassured that previous BSI before HSCT probably increased the risk of BSI (RE 2.28, 95% CI 1.19-4.34, moderate certainty), and revealed that steroid use (RE 2.72, 95% CI 1.31-5.64, moderate certainty) was likely a risk factor while autologous HSCT was probably a protective factor of BSI (RE 0.65, 95% CI 0.45-0.94, moderate certainty).
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10.
Effects of donor-specific antibodies on engraftment and long-term survival after allogeneic hematopoietic stem cell transplantation-A systematic review and meta-analysis
Huang, Y., Luo, C., Wu, G., Huang, X., Ding, Y., Huang, Z., Chen, J., Li, X., Xu, S.
Bone marrow transplantation. 2023
Abstract
The presence of donor-specific antibodies (DSAs) have been reported to be associated with an increased risk of primary graft failure following allogeneic hematopoietic stem cell transplantation (allo-HSCT), but its effects on the time to engraftment and long-term outcomes remain unclear. We performed a systematic review and meta-analysis of studies investigating the impact of DSAs on engraftment and long-term survival of patients undergoing allo-HSCT. We systematically searched PubMed, Embase, the Cochrane Library, and CBM. Data were analyzed using RevMan5.4. Pooled hazard ratio (HR), standard mean difference (SMD) or odds ratio (OR) and corresponding 95% confidence interval (CI) are calculated for time-to-event data, continuous data, discontinuous data respectively. 17 eligible studies were included, involving 2169 patients main receiving haploidentical SCT (haplo-SCT) or umbilical cord blood transplantation (UCBT). Meta-analysis showed that DSAs-positive patients are associated with significantly higher risk of GF(OR = 12.87, 95%CI, 6.45-25.70; P < 0.00001; OR = 4.76, 95%CI, 2.88-7.87), poorer neutrophil engraftment (HR = 2.20, 95%CI, 1.02-4.73; P = 0.04; HR = 1.83, 95%CI, 1.46-2.30; P < 0.00001), worse OS (HR = 3.19, 95%CI, 1.85-5.50; P < 0.0001; HR = 1.68, 95%CI, 1.04-2.71; P = 0.03), and inferior PFS (HR = 4.25, 95%CI, 1.59-11.40; P = 0.004; HR = 4.83, 95%CI, 1.65-14.12; P = 0.004) in haplo-SCT and UCBT, respectively.