Corrigendum: Determining the predictive impact of donor parity on the outcomes of human leukocyte antigen matched hematopoietic stem cell transplants: a retrospective, single-center study.

[This corrects the article DOI: 10.3389/fonc.2024.1339605.].

Immunologic responses to the third and fourth doses of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in cell therapy recipients: a systematic review and meta-analysis.

BACKGROUND: Multiple studies have provided evidence of suboptimal or poor immune responses to SARS-CoV-2 vaccines in recipients of hematopoietic stem cell transplantation (HSCT) and chimeric antigen receptor-T (CAR-T) cell therapy compared to healthy individuals. Given the dynamic nature of SARS-CoV2, characterized by the emergence of many viral variations throughout the general population, there is ongoing discussion regarding the optimal quantity and frequency of additional doses required to sustain protection against SARS-CoV2 especially in this susceptible population. This systematic review and meta-analysis investigated the immune responses of HSCT and CAR-T cell therapy recipients to additional doses of the SARS-CoV-2 vaccines. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, the study involved a comprehensive search across PubMed, Scopus, Web of Science Core Collection, Embase, and Cochrane Biorxiv and medRxiv, focusing on the serological responses to the third and fourth vaccine doses in HSCT and CAR-T cell patients. RESULTS: This study included 32 papers, with 31 qualifying for the meta-analysis. Results showed that after the third dose, the seroconversion rate in HSCT and CAR-T cell therapy recipients who didn't respond to the second dose was 46.10 and 17.26%, respectively. Following the fourth dose, HSCT patients had a seroconversion rate of 27.23%. Moreover, post-third-dose seropositivity rates were 87.14% for HSCT and 32.96% for CAR-T cell therapy recipients. Additionally, the seropositive response to the fourth dose in the HSCT group was 90.04%. CONCLUSION: While a significant portion of HSCT recipients developed antibodies after additional vaccinations, only a minority of CAR-T cell therapy patients showed a similar response. This suggests that alternative vaccination strategies are needed to protect these vulnerable groups effectively. Moreover, few studies have reported cellular responses to additional SARS-CoV-2 vaccinations in these patients. Further studies evaluating cellular responses are required to determine a more precise assessment of immunogenicity strength against SARS-CoV-2 after additional doses.

Rate, Risk Factors, and Outcomes of Invasive Fungal Infections in Patients with Hematologic Malignancies.

Background: Invasive fungal infections (IFIs) are a significant cause of mortality and morbidity in patients with hematological malignancies. Given the considerable prevalence and consequences of IFIs, hence revealing the exact cause of fungal infections, their rate, associated risk factors, and complications could contribute to reducing both financial and life costs, choosing targeted antifungal treatment, and avoiding unnecessary toxic treatments in individuals who are not suffering from mycoses. Materials and Methods: This prospective cross-sectional study was conducted in the first semester of 2019. All patients with hematologic malignancies (HM) admitted to Dr. Shariati Hospital were studied. Only those with probable/proven IFIs defined according to the last update of EORTC/MSG criteria were included in the study. The demographic and clinical data were recorded from the hospital information registration system using a questionnaire. Statistical analysis was performed using SPSS software version 24. Results: Out of 1109 HM patients hospitalized during the study period, 67 (6.04%) IFIs were diagnosed. Of these, 57 (85.04%) were aspergillosis, 7 (10.4%) were mucormycosis, and 3 patients developed other fungal infections. Males constituted 67.2% of the entire IFI population. The mean±SD age of the samples was 43.16 ± 13.8 years. The most common type of malignancy was AML. Lung imaging showed lesions associated with fungal infections in 52 cases (77.6%), with multiple nodules as the most prevalent pattern being observed in 64.2% of cases. Sinus involvement was evidenced in the PNS CT scan of 46 (68.6%) patients. The attributable mortality rate for IFIs was 62.7%. Both the types of IFI and malignancies had no significant relationship with the outcome of patients. Central venous catheter, mucositis, and antibiotic use were the most frequent risk factors. Conclusion:  IFI represents a frequent complication for HM patients with high mortality. Aspergillus species are the predominant etiology in these settings. Considering our results, in high-risk patients, manifestations of warning signs in the sinus and lungs, which would not be cleared despite receiving antibiotics, should raise the possibility of IFIs.

Upregulation of lnc-FOXD2-AS1, CDC45, and CDK1 in patients with primary non-M3 AML is associated with a worse prognosis.

Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy with an unfavorable outcome. The present research aimed to identify novel biological targets for AML diagnosis and treatment. In this study, we performed an in-silico method to identify antisense RNAs (AS-RNAs) and their related co-expression genes. GSE68172 was selected from the AML database of the Gene Expression Omnibus and compared using the GEO2R tool to find DEGs. Antisense RNAs were selected from all the genes that had significant expression and a survival plot was drawn for them in the GEPIA database, FOXD2-AS1 was chosen for further investigation based on predetermined criteria (logFC ≥|1| and P < 0.05) and its noteworthy association between elevated expression level and a marked reduction in the overall survival (OS) in patients diagnosed with AML. The GEPIA database was utilized to investigate FOXD2-AS1-related co-expression and similar genes. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and gene ontology (GO) function analysis of the mentioned gene lists were performed using the DAVID database. The protein-protein interaction (PPI) network was then constructed using the STRING database. Hub genes were screened using Cytoscape software. Pearson correlation analysis was conducted using the GEPIA database to explore the relationship between FOXD2-AS1 and the hub genes. The transcription of the selected coding and non-coding genes, including FOXD2-AS1, CDC45, CDC20, CDK1, and CCNB1, was validated in 150 samples, including 100 primary AML non-M3 blood samples and 50 granulocyte colony stimulating factor (G-CSF)-mobilized healthy donors, using quantitative Real-Time PCR (qRT-PCR). qRT-PCR results displayed significant upregulation of lnc-FOXD2-AS1, CDC45, and CDK1 in primary AML non-M3 blood samples compared to healthy blood samples (P = 0.0032, P = 0.0078, and P = 0.0117, respectively). The expression levels of CDC20 and CCNB1 were not statistically different between the two sets of samples (P = 0.8315 and P = 0.2788, respectively). We identified that AML patients with upregulation of FOXD2-AS1, CDK1, and CDC45 had shorter overall survival (OS) and Relapse-free survival (RFS) compared those with low expression of FOXD2-AS1, CDK1, and CDC45. Furthermore, the receiver operating characteristic (ROC) curve showed the potential biomarkers of lnc -FOXD2-AS1, CDC45, and CDK1 in primary AML non-M3 blood samples. This research proposed that the dysregulation of lnc-FOXD2-AS1, CDC45, and CDK1 can contribute to both disease state and diagnosis as well as treatment. The present study proposes the future evolution of the functional role of lnc-FOXD2-AS1, CDC45, and CDK1 in AML development.

Determining the predictive impact of donor parity on the outcomes of human leukocyte antigen matched hematopoietic stem cell transplants: a retrospective, single-center study.

Introduction: Donor choosing remains to play a pivotal role in allogeneic hematopoietic stem cell transplantation (allo-HSCT). Numerous criteria beyond HLA compatibility impact the selection of a suitable donor. Methods: We evaluated the effect of donor parity on transplant outcomes in a large homogeneously treated population that received an HLA-matched allo-HSCT between 2010 and 2021 at our center. All patients were transplanted from a peripheral blood stem cell source following a myeloablative Busulfan-based conditioning and an identical protocol for graftversus-host disease (GVHD) prophylaxis regimen. Results: A total of 1103 allo-HSCT recipients were included. 188 (17.04%) had transplants from parous female donors, whereas 621 (56.30%) and 294 (26.70%) received transplants from male and nulliparous female donors, respectively. HSCTs from parous female donors compared to male and nulliparous females were associated with a significantly higher incidence of grade III-IV acute (a) GVHD (55.27% vs. 11.34 and 10.84%) and extensive chronic (c) GVHD (64.32% vs. 15.52 and 13.65%), as well as lower relapse incidence (RI). Discussion: This study finds that while parous female donors are associated with higher incidences of grade III-IV aGVHD and extensive cGVHD post-allo-HSCT, the advantages, such as a lower RI, outweigh the risks. The results of our study provide valuable insights for donor selection.

Peer support-based online education, burden of care and quality of life among family caregivers of patients with leukaemia: non-randomised clinical trial.

OBJECTIVE: The responsibility of caring for patients with leukaemia places a heavy burden on family caregivers (FCs) and negatively impacts their quality of life (QoL). This study aimed to investigate the effects of peer support (PS)-based online education programme on the burden of care (BoC) and QoL of FCs of patients with leukaemia. METHODS: This before-after study involved a total of 80 eligible FCs of patients with leukaemia (40 individuals per group). The participants received the necessary information from a researcher and peers through online sessions and WhatsApp group. To collect data, the Zarit Burden Interview and the Caregiver Quality of Life Index-Cancer (CQOLC) had been been completed once before the intervention and once 1 month after the intervention. RESULTS: There was no significant difference between the two groups regarding baseline variables except the mean BoC that was significantly higher in the intervention group (IG) (p<0.001). However, after controlling for the effects of confounding variables, the mean BoC score of participants in IG was significantly lower than that of the control group (p<0.001). Additionally, there was no significant difference between the two groups in terms of CQOLC before (p=0.178) and after (p=0.538) the intervention. CONCLUSION: The PS-based online education programme had a positive impact on reducing the care burden of FCs of patients with leukaemia. This programme can effectively reduce costs, particularly during emergencies and crises such as pandemics, as it eliminates the need for FCs and peers to physically visit hospitals. REGISTRATION: The study was registered at the Iranian Registry of Clinical Trials on 18 July 2021 (IRCT registration number: IRCT20210507051209N1).

No Association of AS3MT Gene Polymorphisms with Susceptibility to Hepatotoxicity in APL Patients Treated with AS2O3: A Single-Center Study.

Background: Arsenic three oxide (As2O3) is the treatment choice for acute promyelocytic leukemia (APL). Little is known about possible risk factors with predictive value for toxicity caused by As2O3. Biomethylation is considered to be a major pathway of detoxification for inorganic arsenics (iAs). Arsenic Methyltransferase (AS3MT) is one of the key enzymes involved in the transfer of a methyl group from S-adenosyl-L-methionine to trivalent arsenical and plays a critical role in arsenic detoxification. Polymorphisms in hAS3MT lead to a change in the catalytic activity of the enzyme and may increase the risk of arsenic-related toxicity. In this study, we investigated the association of the AS3MT polymorphisms (rs11191439, rs3740390, and rs3740393) genes with hepatotoxicity in APL patients treated with As2O3. Materials and Methods: Genotyping was performed in 140 adult patients with APL treated with As2O3 using PCR-RFLP for rs11191439 and tetra-primer ARMS-PCR for rs3740390 and rs3740393. The results of PCR-RFLP and ARMS-PCR were confirmed by direct sequencing of 10 % of DNA samples. The results were analyzed using SNPStats, SPSS, and FinchTV. Hepatotoxicity was graded according to the National Cancer Institute's Common Toxicity Criteria (CTC). Results : Hepatotoxicity was seen in 52 of the 140 patients (37.1%), with grades I and II hepatotoxicity in 40 (28.6%) and grades III and IV hepatotoxicity in 12 (8.5%) patients. The association between the three polymorphisms and hepatotoxicity was evaluated using five genetic models and none of the three studied polymorphisms were significantly associated with hepatotoxicity. Discussion : The results of our study showed that AS3MT rs11191439, rs3740390, and rs3740393 polymorphisms are not associated with hepatotoxicity in APL patients. Genetic polymorphisms in enzymes which are involved in arsenic metabolism have been shown to have ethnicity and race-related differences. To more precisely characterize the association between AS3MT gene polymorphism and hepatotoxicity, future large-scale studies in non-Asian populations and other ethnicities are needed.

The expression changes of PD-L1 and immune response mediators are related to the severity of primary bone tumors.

The expression pattern, diagnostic value, and association of PD-L1, IFN-γ and TGF-ß with bone tumor type, severity, and relapse are determined in this study. 300 human samples from patients with osteosarcoma, Ewing sarcoma, and GCT were enrolled. The PD-L1 gene and protein expression were assessed by qRT-PCR and immunohistochemistry, respectively. ELISA and flow cytometry was used to detect cytokines and CD4/CD8 T cell percentages, respectively. A considerable increase in PD-L1 level was detected in bone tumor tissues at both gene and protein levels that was considerable in osteosarcoma and Ewing sarcoma. A positive correlation was detected regarding the PD-L1 and tumor metastasis and recurrence in osteosarcoma and Ewing sarcoma. The increased IFN-γ level was detected in patients with metastatic, and recurrent osteosarcoma tumors that were in accordance with the level of TGF-ß in these samples. The simultaneous elevation of IFN-γ and TGF-ß was detected in Ewing sarcoma and GCT, also the CD4 + /CD8 + ratio was decreased significantly in patients with osteosarcoma compared to GCT tumors. The elevated levels of PD-L1, TGF- ß, and IFN-γ were associated with bone tumor severity that can provide insights into the possible role of this axis in promoting immune system escape, suppression, and tumor invasion.

Clinical Features and Risk Factors of Relapse and Mortality in Thrombotic Thrombocytopenic Purpura Patients: A Seven-Year Experience.

Background: Thrombotic thrombocytopenic purpura (TTP) is associated with microangiopathic hemolytic anemia, thrombocytopenia, and microvascular thrombosis. No comprehensive report exists on clinical characteristics and risk factors of relapse and mortality in Iranian TTP patients. In this study, we aimed to report clinical features of Iranian TTP patients, to evaluate disease relapse and mortality rate and their associated risk factors. Materials and Methods: This study was a cohort study of patients diagnosed with microangiopathic hemolytic anemia admitted to the Shariati Hospital, Tehran, a referral center for TTP patients, from 2010 to 2017. Demographic, clinical, and laboratory data were recorded and patients were followed for 3 years regarding disease relapse and mortality. Results:  114 patients (80 females, 34 males) with a mean age of 39.3 ± 14.99 years were included.  Hematologic and neurologic symptoms were the most common manifestations. Abnormal laboratory findings at the presentation included thrombocytopenia, anemia, and elevated LDH. All patients were treated with plasma exchange, and 75.5% of them had a response to treatment, while the 3-year relapse and mortality rate was 23.6 and 26.3%.  Lower platelet count was a predictor of disease relapse. Age, hematological, or neurological initial presentation were associated with TTP mortality. Conclusion: Based on the largest study of TTP patients ever in Iran, the demographic and clinical characteristics of Iranian TTP patients are similar to other existing reports. Knowledge of the risk factors for TTP relapse and mortality could be useful to alert hematologists for prompt therapeutic actions when necessary.

Homologous versus Heterologous prime-boost COVID-19 Vaccination in autologous hematopoietic stem cell transplantation recipients: a blinded randomized controlled trial.

Background/Purpose: Optimizing vaccine efficacy is of particular concern in patients undergoing hematopoietic stem cell transplantation (HSCT), which mainly have an inadequate immune response to primary SARS-CoV-2 vaccination. This investigation aimed to explore the potential prime-boost COVID-19 vaccination strategies following autologous (auto-) HSCT. Methods: In a randomized clinical trial, patients who had already received two primary doses of receptor-binding domain (RBD) tetanus toxoid (TT) conjugated SARS-CoV-2 vaccine during three to nine months after auto-HSCT were randomized to receive either a homologous RBD-TT conjugated or heterologous inactivated booster dose four weeks after the primary vaccination course. The primary outcome was comparing the anti-S IgG Immune status ratio (ISR) four weeks after the heterologous versus homologous booster dose. The assessment of safety and reactogenicity adverse events was considered as the secondary outcome. Results: Sixty-one auto-HSCT recipients were recruited and randomly assigned to receive either homologous or heterologous booster doses four weeks after the primary vaccination course. The mean ISR was 3.40 (95% CI: 2.63- 4.16) before the booster dose with a 90.0% seropositive rate. The ISR raised to 5.12 (95% CI: 4.15- 6.08) with a 100% seropositive rate after heterologous (P= 0.0064) and to 3.42 (95% CI: 2.67- 4.17) with a 93.0% seropositivity after the homologous booster doses (P= 0.96). In addition, the heterologous group suffered more AEs following the booster dosage than the homologous group, but this difference was not statistically significant (p = 0.955). In multivariable analysis, the prime-boost vaccination strategy (heterologous versus homologous), the level of ISR before the booster dose, and the length of time between auto-HSCT and booster dose were the positive predictors of serologic response to a booster dose. No serious adverse event is attributed to booster vaccination. Conclusion: In patients who were primed with two SARS-CoV-2 vaccine doses during the first year after auto-HSCT, heterologous prime-boost COVID-19 vaccination with inactivated platform resulted in considerably enhanced serologic response and non-significantly higher reactogenicity adverse events than homologous RBD-TT conjugated prime-boost COVID-19 vaccination strategy.

Vincristine-Induced Seizure from Drug Interactions: A Case Report and Review of Literature.

Vincristine (VCR) as a key drug for the treatment of acute lymphoblastic leukemia (ALL) is associated with neurotoxicity. We present a young man with a history of controlled childhood seizures who was diagnosed with pre-B-cell ALL and developed generalized tonic-clonic seizures following the Cancer and Leukemia Group B (CALGB) 8811 regimen. The patient also received oral itraconazole to prevent fungal infection initiated by chemotherapy. Possible causes of seizure, including electrolyte abnormalities, hypoglycemia, central nervous system infection or inflammation, were ruled out. According to the Naranjo Adverse Drug Reaction Scale, the patient's seizure had been attributed to VCR, possibly secondary to concomitant use of itraconazole and doxorubicin. The patient successfully recovered after discontinuation of VCR and supportive care. Clinicians should be aware of the possibility of vincristine-induced seizure in adult patients, especially with the concomitant use of drugs known to have potential drug-drug interactions.

Three doses of a recombinant conjugated SARS-CoV-2 vaccine early after allogeneic hematopoietic stem cell transplantation: predicting indicators of a high serologic response-a prospective, single-arm study.

Background: Allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients must be vaccinated against SARS-CoV-2 as quickly as possible after transplantation. The difficulty in obtaining recommended SARS-CoV-2 vaccines for allo-HSCT recipients motivated us to utilize an accessible and affordable SARS-CoV-2 vaccine with a recombinant receptor-binding domain (RBD)-tetanus toxoid (TT)-conjugated platform shortly after allo-HSCT in the developing country of Iran. Methods: This prospective, single-arm study aimed to investigate immunogenicity and its predictors following a three-dose SARS-CoV-2 RBD-TT-conjugated vaccine regimen administered at 4-week (± 1-week) intervals in patients within 3-12 months post allo-HSCT. An immune status ratio (ISR) was measured at baseline and 4 weeks (± 1 week) after each vaccine dose using a semiquantitative immunoassay. Using the median ISR as a cut-off point for immune response intensity, we performed a logistic regression analysis to determine the predictive impact of several baseline factors on the intensity of the serologic response following the third vaccination dose. Results: Thirty-six allo-HSCT recipients, with a mean age of 42.42 years and a median time of 133 days between hematopoietic stem cell transplant (allo-HSCT) and the start of vaccination, were analyzed. Our findings, using the generalized estimating equation (GEE) model, indicated that, compared with the baseline ISR of 1.55 [95% confidence interval (CI) 0.94 to 2.17], the ISR increased significantly during the three-dose SARS-CoV-2 vaccination regimen. The ISR reached 2.32 (95% CI 1.84 to 2.79; p = 0.010) after the second dose and 3.87 (95% CI 3.25 to 4.48; p = 0.001) after the third dose of vaccine, reflecting 69.44% and 91.66% seropositivity, respectively. In a multivariate logistic regression analysis, the female sex of the donor [odds ratio (OR) 8.67; p = 0.028] and a higher level donor ISR at allo-HSCT (OR 3.56; p = 0.050) were the two positive predictors of strong immune response following the third vaccine dose. No serious adverse events (i.e., grades 3 and 4) were observed following the vaccination regimen. Conclusions: We concluded that early vaccination of allo-HSCT recipients with a three-dose RBD-TT-conjugated SARS-CoV-2 vaccine is safe and could improve the early post-allo-HSCT immune response. We further believe that the pre-allo-HSCT SARS-CoV-2 immunization of donors may enhance post-allo-HSCT seroconversion in allo-HSCT recipients who receive the entire course of the SARS-CoV-2 vaccine during the first year after allo-HSCT.

Early Vitrectomy: An Effective Treatment for Acute Postcataract Surgery Endophthalmitis.

Background: Endophthalmitis is a rare but a high morbid complication after cataract surgery, and a gold standard treatment is not recommended yet. In this study, we aim to evaluate the effect of early vitrectomy on the visual acuity of patients with postcataract endophthalmitis. Materials and Methods: This study was a single-arm clinical trial on 27 patients with postcataract surgery endophthalmitis. Early vitrectomy was the intervention. Visual acuity as the primary outcome was evaluated and compared at baseline, at discharge, and 1 and 3 months after the intervention. Results: From 27 patients who included in our study, six patients gain favorable visual acuity of 5/10 and above (success rate = 22%), and four of them have no improvement in their visual acuity. Retinal detachment was reported as a complication in just one case. Negative culture was a predictor for success in terms of visual acuity after the surgery. All patients who gain favorable results, presented in the first 15 days after the cataract surgery. Conclusion: The result of our study showed that, considering complete, early vitrectomy for the treatment of postcataract surgery endophthalmitis, especially for those who presented in the first 15 days of cataract surgery and for those who have negative culture is promising.

Comparable Outcomes of Pre- Versus Post-Tyrosine Kinase Inhibitor Era Treatment in Chronic Myeloid Leukemia: A Retrospective Cohort Study With Long-term Follow-up.

Imatinib, a selective BCR-ABL tyrosine kinase inhibitor (TKI), was introduced after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for patients with chronic myeloid leukemia (CML). However, the long-term effects of allo-HSCT in chronic phase CML patients are mostly unknown. We retrospectively analyzed the outcomes of 204 patients with sibling donors who received peripheral stem cells and underwent allo-HSCT of chronic phase I (CP1) in the pre- and post-TKI era at Shariati Hospital in Tehran, Iran, from 1998 to 2017 and followed up till the end of 2021. The median follow-up time for all patients was 8.7 (SD = 0.54) years. Fifteen-year overall survival (OS), disease-free survival (DFS), graft-versus-host disease-free relapse-free survival (GRFS), relapse, and non-relapse mortality (NRM) incidence were 65.70%, 57.83%, 17.56%, 13.17%, and 28.98%, respectively. Using multivariable analyses, the only risk factor increasing the hazard of death was the time between diagnosis to allo-HSCT greater than 1 year compared to this time less than 1 year by 74% [hazard ratio (HR) = 1.74, P = 0.039]. Also, age is a significant risk factor for DFS (HR = 1.03, P = 0.031). Our findings suggested that allo-HSCT is still an important treatment option for CP1 patients, especially those resistant to TKI treatment. TKI consumption can have a desirable effect on NRM after allo-HSCT for CP1 CML.

Evaluation of Safety and Immunogenicity of a Recombinant Receptor-Binding Domain (RBD)-Tetanus Toxoid (TT) Conjugated SARS-CoV-2 Vaccine (PastoCovac) in Recipients of Autologous Hematopoietic Stem Cell Transplantation Compared to the Healthy Controls; A Prospective, Open-Label Clinical Trial.

Background: The urgent need for prompt SARS-CoV-2 immunization of hematopoietic stem cell transplant (HSCT) recipients in an endemic area raises many challenges regarding selecting a vaccine platform appropriate for HSCT recipients being economical for widespread use in developing countries. Methods: The trial is a prospective, single-group, open-label study to investigate the safety and serologic response of two doses of the recombinant receptor-binding domain (RBD)-Tetanus Toxoid (TT) conjugated SARS-CoV-2 vaccine (PastoCovac) early after autologous (auto) HSCT. For this reason, a total of 38 patients who completed the two-dose SARS-CoV-2 RBD-based vaccine between three to nine months after auto-HSCT and had an available anti-spike serologic test at three predefined time points of baseline and after the first and second doses and 50 healthy control individuals were included in the analysis. The primary outcome was defined as an increase in IgG Immune status ratio (ISR) to the cut-off value for the positive result (≥1.1) in the semiquantitative test. Findings: The median time between auto-HSCT and vaccination was 127 days. No participant reported any significant adverse effects (Grade 3). Pain at the injection site was the most common adverse event. The ISR increased significantly (p < 0.001) during the three-time point sampling for both patients and healthy control groups. In patients, the mean ISR increased from 1.39 (95% CI: 1.13−1.65) at baseline to 2.48 (1.93−3.03) and 3.73 (3.13−4.38) following the first and second dosages, respectively. In multivariate analysis, the higher count of lymphocytes [OR: 8.57 (95% CI: 1.51−48.75); p = 0.02] and history of obtaining COVID-19 infection before transplantation [OR: 6.24 (95% CI: 1.17−33.15); p = 0.03] remained the predictors of the stronger immune response following two doses of the RBD-TT conjugated vaccine. Moreover, we found that the immunogenicity of the COVID-19 vaccine shortly after transplantation could be influenced by pre-transplant COVID-19 vaccination. Interpretation: The RBD-TT conjugated SARS-CoV-2 vaccine was safe, highly immunogenic, and affordable early after autologous transplants. Funding: This work was mainly financed by the Hematology-Oncology-Stem Cell Transplantation Research Center (HORCSCT) of Tehran University and the Pasteur Institute of Iran.

Adherence to practice guidelines for the management of febrile neutropenia in patients undergoing hematopoietic stem cell transplantation: An observational study in a referral center in Iran.

INTRODUCTION: Patients undergoing hematopoietic stem cell transplantation (HSCT) are suspected to develop febrile neutropenia (FN) and severe infections. Therefore, appropriate prescription of antibiotics in these patients is crucial to reduce the rates of morbidity, mortality, and antimicrobial resistance. The present study aimed to evaluate the physicians' prescription and adherence to the FN clinical guidelines among patients undergoing HSCT. METHODS: This prospective observational single-center study was conducted during a 15-month period in a tertiary referral hospital in Iran. The patients with at least one episode of FN following HSCT were included in the current study. The physicians' adherence to the Infectious Diseases Society of America (IDSA) and National Comprehensive Cancer Network (NCCN) clinical guidelines for the management of FN was evaluated using prescription data and medical record reviews. RESULTS: Two hundred and fifteen patients with 297 FN episodes were evaluated. The timing of antibiotics and the selection of the initial regimen were considered guideline-based therapy. However, antibiotic dosing and initial regimen modification were not followed in terms of the guideline recommendations in 58.1% of the patients. In particular, vancomycin was inappropriately given in 83.1% of patients. The overall adherence of physicians to the guidelines was 35.8%. CONCLUSION: Non-adherence to clinical guidelines is high particularly in initial regimen modification and administration of vancomycin, which affects hospital stay and patient's outcome. Implementation of guideline-review sessions to raise the awareness of the physicians and to improve the rational use of antimicrobial agents may be crucial.

A Panel of Circulating microRNAs as a Potential Biomarker for the Early Detection of Gastric Cancer.

Background: The high mortality rate of Gastric Cancer (GC) is a consequence of delayed diagnosis. The early diagnosis of GC could increase the five-year survival rate among patients. We aimed to find a panel of microRNAs (miRNA) for the detection of GC in the early stages. Methods: In this case-control study, we selected consistently upregulated miRNAs from the results of 12 high-throughput miRNA profiling studies in GC. In the profiling phase, the differential expressions of 13 candidate miRNAs were analyzed by quantitative reverse-transcription PCR (qRT-PCR) in two pooled RNA samples prepared from the plasma of eight GC patients and eight matched controls. In the validation phase, significantly upregulated miRNAs from the profiling phase were further evaluated in the plasma samples of 97 patients with stage I-IV gastric adenocarcinoma and 100 healthy controls. Results: In the profiling phase, six miRNAs (miR-18a, 21, 25, 92a, 125b and 221) were significantly upregulated in the GC patients compared to the controls (p<0.05). However, in the validation phase, only significant up-regulation of miR-18a, 21 and 125b was confirmed (p<0.05). A panel of miR-18a/21/125b was able to detect GC patients with stage I-IV from the controls (p<0.001; AUC=0.92, sensitivity=86%; specificity=85%). In addition, the panel could distinguish the early-stage GC (I+II) from the control group with an AUC of 0.83, a sensitivity of 83%, and a specificity of 75%. Conclusion: A panel of circulating miR18a/21/125b could be suggested as a potential biomarker for the early detection of GC.

Incidence and Prognostic Impact of WT-1 Gene Exon7 and 9 Mutations in Acute Promyelocytic Leukemia.

Background: Wilms' tumor suppressor gene 1 (WT1) gene mutation has been reported to be a prognostic factor in normal-cytogenetic acute myeloid leukemia (AML) patients. Higher rates of mutation in the WT1 gene have been reported in several tumors including normal-cytogenetic AML patients. Data regarding WT1 mutations in acute promyelocytic leukemia (APL) is very scarce. In this study, we evaluated the incidence and impact of WT1 mutation on the outcome of APL patients. Materials and Methods: A total of 92 patients diagnosed with APL were studied in three distinct groups: early mortality, relapsed, and persistent complete remission. Genomic DNA of bone marrow samples of patients was analyzed. For quantification of expression levels of the WT1 gene, real-time quantitative PCR (rqPCR) was performed by a real-time PCR system. WT1 mutation and its impact on prognosis were considered the primary endpoint of the study. Statistical analysis was performed with STATA. Results: WT1 mutation frequency was 6.25% in the early mortality group (1/16 patients), 13.16% in the relapse group (5/38 patients), and 7.89% in the persistent complete remission group (3/38 patients). 8 mutations were in exon 7 and one mutation in exon 9. WT1 mutation in the relapse group was associated with a trend toward worse disease-free survival (DFS) while overall survival (OS) was not affected by WT1 mutation in univariate analysis. Patients with no mutations in WT1 and FLT3/ITD had better overall survival and disease-free survival compared to patients with mutations in the WT1 gene or FLT3/ITD in the relapse group. Conclusion: The frequency of WT1 gene mutations does not differ significantly between patients with early mortality, relapse, and persistent complete remission. The presence of WT1 mutation is associated with higher relapse and lower survival rates in relapse group patients.

Modified combination of anti-thymocyte globulin (ATG) and post-transplant cyclophosphamide (PTCy) as compared with standard ATG protocol in haploidentical peripheral blood stem cell transplantation for acute leukemia.

In haploidentical peripheral blood stem cell transplantation (haplo-PBSCT), the combination of anti-thymocyte globulin and post-transplant cyclophosphamide (ATG/PTCy) has a synergistic impact in preventing graft-versus-host disease (GvHD). However, little is known about the long-term consequences of the new combination approach. Our goal is to evaluate the efficacy of ATG/PTCy versus a standard ATG regimen by focusing at long-term outcomes in a more homogeneous group of patients. We retrospectively included 118 adult patients up to 60 years with acute leukemia who underwent haplo-PBSCT at our single institution, following the same myeloablative conditioning regimen. From 2010 to 2020, 78 patients received a modified combination of ATG (2.5 mg/kg/day, on days -3, -2, and -1) and PTCy (40 mg/kg/day on days +3 and +4) compared to 40 patients who had a standard ATG-based regimen (2.5 mg/kg/day from days -4 to -1) from 2008 to 2015. The median follow-up time for all patients was 5.36 years, respectively. The cumulative incidence (CI) of neutrophil and platelet engraftment, as well as CMV reactivation, did not differ statistically between the two groups. The CI of the acute GvHD of grades II-IV and III-IV and extensive chronic GvHD were considerably lower in the ATG/PTCy (34.6%, 8.97%, and 13.63%) than in the ATG cohort (57.5%, 30%, and 38.23%) as validated by multivariable modeling. Additionally, compared to the ATG arm, the ATG/PTCy was a hazard factor associated with a higher risk of relapse (HR = 2.23, p = 0.039). The probability of 5-year overall survival, disease-free survival, and GvHD-free relapse-free survival in the ATG/PTCy group (53.34%, 49.77%, and 36.04%) was comparable with the ATG group (47.5%, 42.5%, and 22.5%), respectively. Our finding suggested that a modified ATG/PTCy combination resulted in a lower risk of acute and chronic GvHD and a higher risk of relapse than the standard ATG-based protocol but had no effect on long-term outcomes. However, certain adjustments in the immunosuppression protocol are warranted to improve the outcome.