scholarly journals Factors Associated with Outcomes Among Refractory/Relapsed TP53-Mutated/Chromosome 17p Deletion Acute B-Cell Lymphoblastic Leukemia (B-ALL) Patients Treated with CD19-Targeted Chimeric Antigen Receptor (CAR)-T Therapy

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3828-3828
Author(s):  
Xian Zhang ◽  
Gailing Zhang ◽  
Wenqian Li ◽  
Yang Zhang ◽  
Tong Wang ◽  
...  
Keyword(s):  
Tp53 Mutation ◽  
Pediatric Patients ◽  
Lymphoblastic Leukemia ◽  
Factors Affecting ◽  
Tp53 Mutations ◽  
Factors Associated ◽  
Car T ◽  
Two Factors ◽  
Chromosome 17P Deletion

Abstract Introduction CD19-targeted chimeric antigen receptor (CAR)-T cell therapy effective for refractory/relapsed (R/R) B-cell acute lymphoblastic leukemia (B-ALL) that results in about 90% of complete remission (CR)/CR with incomplete blood recovery (CRi). According to a published study from our center that analyzed 254 R/R B-ALL patients, we confirmed that TP53 mutation was an independent prognostic factor of efficacy following CD19 CAR-T therapy. What factors affect the prognosis of patients with TP53 mutation/deletion treated with CD19 CAR-T is not clear. Here, we focus on the patients with TP53 mutation/deletion and analyze the factors associated with efficacy following CD19 CAR-T therapy among 64 B-ALL patients with TP53 mutation/chromosome 17p deletion. Patients and Methods From June 2017 to February 2020, we analyzed 64 R/R patients (36 male, 28 female) with TP53 mutation/chromosome 17p deletion who received CD19 CAR T-cells from 5 clinical trials at Hebei Yanda Lu Daopei Hospital (NCT03173417, NCT02546739, NCT03312205 and NCT03671460 registered at https://clinicaltrials.gov; Chictr-onc-17012829 at www.chictr.org.cn). Among them, there were 42 patients with TP53 mutation only, 10 with chromosome 17p deletion, and 12 harboring both the mutation and deletion. There were 27 pediatric patients ≤ 14 years old and the remaining 37 patients were adults (>14 years old). Results After CAR-T therapy, 49/64 (76.6%) patients achieved CR/CRi on Day 30 and 1-year OS among the 64 patients was 39.4%. Other 15 patients who had no response (NR) to CAR-T therapy died within 1 year. Among the 49 patients who achieved CR after CD19 CAR-T, 1-year OS and 1-year relapse-free survival (RFS) were 50.0% and 40.9%, respectively. Thirty-three of the 49 patients subsequently bridged to allogeneic hematopoietic stem cell transplantation (allo-HSCT) with 1-year OS and RFS of 59.5% and 55.8%, respectively. Using univariate analysis of CR rates (Table 1), the pediatric patients demonstrated a lower CR rate compared to the adult patients (63.0% vs. 86.5%, p=0.04). We saw a trend of patients with complex cytogenetics having a relatively low CR rate compared to patients without complex cytogenetics yet no significant difference was observed (69.4% vs.85.7%, p= 0.15). For the TP53 functional mutation group versus the TP53 non-functional mutation group, CR rates were 70.0% vs. 92.8%, respectively (p= 0.15). In addition, patients with more than one TP53 mutations (≥ 2) showed a lower CR rate of 72.3% compared to patients with one TP53 mutation who achieved 100% CR (p= 0.18). Analyzing the data from all 64 patients, we identified three factors that were significantly associated with OS: 1) presence of complex cytogenetics (compared to without complex cytogenetics; p= 0.005), 2) achievement of CR/CRi (compared to NR; p< 0.001), and 3) bridging into allo-HSCT post CAR-T (compared to CAR-T only; p < 0.001). Next, we focused on analyzing the factors affecting the long-term efficacy of the 49 patients who achieved CR (Table 2). Two factors were associated with OS/RFS: 1) presence of complex cytogenetics (compared to no complex cytogenetics; 1-year OS of 60.1% vs. 39.8%, p=0.025; 1-year RFS 52.0% vs. 28.6%, p = 0.004, Figure 1), and 2) bridging into allo-HSCT post CAR-T (compared to CAR-T only; 1-year OS 59.5% vs. 28.1%, p = 0.003; 1-year RFS 55.8% vs. 7.7%, P < 0.001, Figure 2). Four additional factors that showed a trend of worse efficacy were 1) TP53 mutations more than one (≥2) (compared to one TP53 mutation; 1-year 53% vs. 21.4%, p=0.06; 1-year RFS 45.4% vs. 14.3%, p=0.15), 2) presence of TP53 mutations plus additional gene mutations (compared to TP53 mutation alone; 61% vs. 34.5%, p=0.07), 3) patients with extramedullary disease (EMD) (compared to without EMD; 1-year OS 59.6% vs. 20%, p= 0.05; 1-year RFS 47.7% vs. 20%, p=0.15), and 4) low risk evolutionary action score (EAp53) (compared to high risk; 1-year RFS 80% vs. 30.6%, p=0.12). Conclusions This study has uncovered factors that may predict treatment outcomes and duration of remission for patients with TP53 mutation/chromosome 17p deletion who received CD19 CAR-T therapy. Presence of complex cytogenetics and not bridging into allo-HSCT are two factors affecting the long-term efficacy. Further studies are needed to confirm these results, to improve the clinical management and personalization of treatment approaches for B-ALL patients harboring TP53 mutation/chromosome 17p deletion. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Cost-Effectiveness of Chimeric Antigen Receptor T-Cell Therapy in Pediatric Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia

2018 ◽  
Vol 111 (7) ◽  
pp. 719-726 ◽  
Author(s):  
Reith R Sarkar ◽  
Nicholas J Gloude ◽  
Deborah Schiff ◽  
James D Murphy
Keyword(s):  
Cost Effectiveness ◽  
Pediatric Patients ◽  
Remission Rate ◽  
Lymphoblastic Leukemia ◽  
Cost Effective ◽  
Standard Of Care ◽  
Health Utility ◽  
Car T ◽  
Cell Acute Lymphoblastic Leukemia

AbstractBackgroundChimeric antigen receptor T-cell (CAR-T) therapy is a promising new class of cancer therapy but has a high up-front cost. We evaluated the cost-effectiveness of CAR-T therapy among pediatric patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL).MethodsWe built a microsimulation model for pediatric patients with relapsed/refractory B-ALL receiving either CAR-T therapy or standard of care. Outcomes included costs, quality of life (health utility), complications, and survival. We measured cost-effectiveness with the incremental cost-effectiveness ratio (ICER), with ICERs under $100 000 per quality-adjusted life-year (QALY) considered cost effective. One-way and probabilistic sensitivity analyses were used to test model uncertainty.ResultsCompared to standard of care, CAR-T therapy increased overall cost by $528 200 and improved effectiveness by 8.18 QALYs, resulting in an ICER of $64 600/QALY. The model was sensitive to assumptions about long-term CAR-T survival, the complete remission rate of CAR-T patients, and the health utility of long-term survivors. The base model assumed a 76.0% one-year survival with CAR-T, although if this decreased to 57.8%, then CAR-T was no longer cost effective. If the complete remission rate of CAR-T recipients decreased from 81% to 56.2%, or if the health utility of disease-free survivors decreased from 0.94 to 0.66, then CAR-T was no longer cost effective. Probabilistic sensitivity analysis found that CAR-T was cost effective in 94.8% of iterations at a willingness to pay of $100 000/QALY.ConclusionCAR-T therapy may represent a cost-effective option for pediatric relapsed/refractory B-ALL, although longer follow-up of CAR-T survivors is required to confirm validity of these findings.

Monoallelic TP53 inactivation is associated with poor prognosis in chronic lymphocytic leukemia: results from a detailed genetic characterization with long-term follow-up

Blood ◽  
2008 ◽  
Vol 112 (8) ◽  
pp. 3322-3329 ◽  
Author(s):  
Thorsten Zenz ◽  
Alexander Kröber ◽  
Katrin Scherer ◽  
Sonja Häbe ◽  
Andreas Bühler ◽  
...  
Keyword(s):  
Tp53 Mutation ◽  
Direct Sequencing ◽  
Clonal Evolution ◽  
Lymphocytic Leukemia ◽  
Prognostic Impact ◽  
Clone Size ◽  
Tp53 Mutations ◽  
Long Term Follow Up ◽  
Serial Samples

AbstractThe exact prognostic role of TP53 mutations (without 17p deletion) and any impact of the deletion without TP53 mutation in CLL are unclear. We studied 126 well-characterized CLL patients by direct sequencing and DHPLC to detect TP53 mutations (exons 2-11). Most patients with 17p deletions also had TP53 mutations (81%). Mutations in the absence of 17p deletions were found in 4.5%. We found a shorter survival for patients with TP53 mutation (n = 18; P = .002), which was more pronounced when analyzed from the time point of mutation detection (6.8 vs 69 months, P < .001). The survival was equally poor for patients with deletion 17p plus TP53 mutation (7.6 months, n = 13), TP53 mutation only (5.5 months, n = 5), and 17p deletion only (5.4 months, n = 3). The prognostic impact of TP53 mutation (HR 3.71) was shown to be independent of stage, VH status, and 11q and 17p deletion in multivariate analysis. Serial samples showed evidence of clonal evolution and increasing clone size during chemotherapy, suggesting that there may be patients where this treatment is potentially harmful. TP53 mutations are associated with poor sur-vival once they occur in CLL. The de-monstration of clonal evolution under selective pressure supports the biologic significance of TP53 mutations in CLL.

scholarly journals Association of Bacteremic Sepsis With Long-term Neurocognitive Dysfunction in Pediatric Patients With Acute Lymphoblastic Leukemia

2018 ◽  
Vol 172 (11) ◽  
pp. 1092 ◽  
Author(s):  
Yin Ting Cheung ◽  
Aaron Eskind ◽  
Hiroto Inaba ◽  
Melissa M. Hudson ◽  
Ching-Hon Pui ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Pediatric Patients ◽  
Lymphoblastic Leukemia ◽  
Neurocognitive Dysfunction

scholarly journals Landscape of driver mutations and their clinical impacts in pediatric B-cell precursor acute lymphoblastic leukemia

2020 ◽  
Vol 4 (20) ◽  
pp. 5165-5173
Author(s):  
Hiroo Ueno ◽  
Kenichi Yoshida ◽  
Yusuke Shiozawa ◽  
Yasuhito Nannya ◽  
Yuka Iijima-Yamashita ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Tp53 Mutation ◽  
Lymphoblastic Leukemia ◽  
Genetic Alterations ◽  
Cell Precursor ◽  
Tp53 Mutations ◽  
Positive Correlations ◽  
Panel Sequencing

Abstract Recent genetic studies using high-throughput sequencing have disclosed genetic alterations in B-cell precursor acute lymphoblastic leukemia (B-ALL). However, their effects on clinical outcomes have not been fully investigated. To address this, we comprehensively examined genetic alterations and their prognostic impact in a large series of pediatric B-ALL cases. We performed targeted capture sequencing in a total of 1003 pediatric patients with B-ALL from 2 Japanese cohorts. Transcriptome sequencing (n = 116) and/or array-based gene expression analysis (n = 120) were also performed in 203 (84%) of 243 patients who were not categorized into any disease subgroup by panel sequencing or routine reverse transcription polymerase chain reaction analysis for major fusions in B-ALL. Our panel sequencing identified novel recurrent mutations in 2 genes (CCND3 and CIC), and both had positive correlations with ETV6-RUNX1 and hypodiploid ALL, respectively. In addition, positive correlations were also newly reported between TCF3-PBX1 ALL with PHF6 mutations. In multivariate Cox proportional hazards regression models for overall survival, TP53 mutation/deletion, hypodiploid, and MEF2D fusions were selected in both cohorts. For TP53 mutations, the negative effect on overall survival was confirmed in an independent external cohort (n = 466). TP53 mutation was frequently found in IGH-DUX4 (5 of 57 [9%]) ALL, with 4 cases having 17p LOH and negatively affecting overall survival therein, whereas TP53 mutation was not associated with poor outcomes among NCI (National Cancer Institute) standard risk (SR) patients. A conventional treatment approach might be enough, and further treatment intensification might not be necessary, for patients with TP53 mutations if they are categorized into NCI SR.

Sedation practices in pediatric ALL patients.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e21500-e21500
Author(s):  
Bethany D. Nugent ◽  
Peter J. Davis ◽  
Robert Noll ◽  
Jean M. Tersak
Keyword(s):  
Pediatric Patients ◽  
Lymphoblastic Leukemia ◽  
Cancer Control ◽  
Future Research ◽  
Neurocognitive Deficits ◽  
Long Term Effects ◽  
Pediatric All ◽  
Behavior Learning ◽  
Repeated Doses

e21500 Background: The 5-year survival rate for pediatric acute lymphoblastic leukemia (ALL) is greater than 90%. A common late effect of pediatric ALL is neurocognitive deficits, such as lower IQ. In recent years, the use of sedation during lumbar punctures (LPs) for treatment of pediatric ALL is becoming increasingly widespread. These patients are exposed to repeated doses of sedatives. Among the most common Children’s Oncology Group (COG) ALL protocols, approximately 30 LPs are performed over a period of 2-3 years. Studies in animals (both rodents and primates) have revealed that common sedation drugs cause harm to the developing brain and can negatively affect behavior, learning, and memory. Gaps in knowledge exist regarding their use in children, particularly with repeated exposures. For children with ALL, little is known about sedation practices such as how commonly sedation is used; what medications are most common; and who administers the medications. The purpose of this study is to summarize sedation practices at COG institutions for LPs related to treatment of pediatric ALL. Methods: All Responsible Investigators (RIs) of the Cancer Control Committee (a subcommittee of COG) were invited to complete an internet-based survey about sedation practices for ALL patients at their institution. Results: Surveys were sent out to 103 RIs with a 62.1% response rate ( N = 64). A combined 2018 new patients with ALL were seen each year ( M = 31.5, range = 3-110); of these patients, 95.7% received sedation for LPs. While there was considerable variability across institutions in medications used (general anesthesia, Propofol with opioid and/or Versed, Versed and opioid, other), the most common was Propofol alone ( n = 36, 56.3%). Anesthesiologists administered sedation at the majority of institutions ( n = 36, 56.3%) while trained sedationists, oncologists, and nurses administered sedation at other institutions. Conclusions: A substantial number of pediatric patients with ALL receive sedation for LPs. However, there is much variation in the types of medications administered and who is administering these medications. Better understanding of sedation practices in children with ALL may inform future research to investigate which methods of sedation are safest, with a particular emphasis on its long-term effects.

scholarly journals CD19-Directed Fast CART Therapy for Relapsed/Refractory Acute Lymphoblastic Leukemia: From Bench to Bedside

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1340-1340 ◽  
Author(s):  
Cheng Zhang ◽  
Jiaping He ◽  
Li Liu ◽  
Jishi Wang ◽  
Sanbin Wang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Lymphoblastic Leukemia ◽  
Preclinical Study ◽  
Car T Cells ◽  
Car T ◽  
Manufacturing Time ◽  
Grade Iii

Background CAR-T targeting CD19 has been a success in treating B-cell acute lymphoblastic leukemia (B-ALL). However, relapse rate is high and the long term survival in pateints is not satisfactory, which is partly due to the limited expansion and persistence of the conventionally-manufactured CAR-T cells. In addition, long manufacturing time and high cost of CAR-T product further limit the wider applications of CAR-T therapy. To solve these issues, we have developed a new manufacturing platform, FasT CAR-T, which shorten the manufacturing time to one day as compared to the conventional CAR-T manufacturing time of 9-14 days, which is critical for patients with rapidly progressing disease. More importantly, CD19-directed FasT CAR-T has been shown to have superior expansion capability, younger and less exhausted phenotype, and higher potency in eliminating B-ALL both in vitro and in vivo. Based on the preclinical study, we initiated a multi-center clinical study to determine the safety, feasibility and efficacy of CD19-FasT CAR-T in treating patients with CD19+ relapsed/refractory B-ALL. Methods CD19-directed CAR-T was manufactured using the FasT CAR-T platform. Peripheral blood (PB) mononuclear cells were obtained by leukapheresis and T cells were separated. CD19-FasT CAR-T manufacturing were all successful. Conventional CAR-T (C-CAR-T) from healthy donor were also made in parallel for comparison in preclinical study. From Dec. 2018 to July 2019, 10 adult CD19+ R/R ALL patients were recruited and all patients received fludarabine and cyclophosphamide as pre-conditioning followed by a single CAR-T infusion 48-72 hours later. Doses used in this study were: 3 DL1 (5 x 104 CAR+ T/kg), 4 DL2 (1 x 105 CAR+ T/kg), and 3 DL3 (1.5 x 105 CAR+ T/kg). The endpoints of the study were clinical toxicity, feasibility, PK of CAR-T and efficacy. Results: In comparison to conventional CAR-T cells, CD19-FasT CAR-T cells had several key features (Table 1). 1) More robust expansion. Upon antigen stimulation, the FasT CAR-T proliferated 5-30 times stronger than that of C-CAR-T. 2) Higher percentage of CD62L+CD45RO- (Tscm) and CD62L+CD45+ (Tcm) population in FasT CAR-T. 3) Lower expression of PD-1+, LAG3+ and Tim3+ in FasT CAR-T. 4). More potent in eliminating Raji tumor in an in vivo xenograft mouse model. 5) More efficient migration to bone marrow which is likely due to the higher expression of CXCR4 on the FasT CAR-T cells. The trial was conducted during Dec. 2018 to July 2019. The pre-treatment bone marrow (BM) blasts were &lt; 5% in 5 cases, 5%-50% in 3 cases, and &gt;50% in 2 cases (Table 2). All 10 patients achieved complete remission (CR) 4 weeks after FasT CAR-T infusion, and 9 were with negative minimal residual disease (MRD-). CAR-T cells proliferation and persistence in peripheral blood (PB) were monitored by qPCR and flow cytometry. CAR-T cells peaked at Day 10 (range Day 8-13) after infusion. The median persistence period of CAR-T in PB was 56 days ((range 28-212 days) after infusion, and the longest persistence is 7 months and still being monitored at the last follow-up. The median peak of CAR copy number is 90,446/mg DNA (range 4,670-247,507/mg DNA) (Figure). The major adverse event was cytokine release syndrome (CRS) which was observed in 9 patients, including 1 patient with grade IV in DL3 group, 3 grade III, 4 grade II and 1 grade I. The clinical manifestation of CRS mainly included fever and hypotension. The median time to the development of CRS was 5 days (2-10 days), and the peak body temperature was at Day 7 (Day 5- 11) and fever lasted for an average of 5 days (3-8 days). Serum IL-6 level increased and peaked on Day 7 post-infusion, which coincided with fever but slightly preceded the CAR-T expansion peak. Three patients experienced CAR-related encephalopathy syndrome (CRES) after CAR-T infusion, in which 1 was grade III CRES. All patients who developed CRS or CRES recovered after intervention. Conclusion FasT CAR-T have superior expansion capacity with younger and less exhausted phenotype, and more potent cytotoxicity against B-ALL. This first-in-human clinical study in China showed CD19-directed FasT CAR-T therapy is highly effective in treating R/R B-ALL with manageable toxicity. The safety, efficacy and potential long-term clinical benefit of FasT CAR-T therapy will be further evaluated in large multi-center trial. (http://www.chictr.org.cn/listbycreater.aspx:ChiCTR1900023212) Disclosures No relevant conflicts of interest to declare.

scholarly journals TP53 and KRAS Variants at Initial Diagnosis Identify an Ultra-High Risk Group of Pediatric T-Lymphoblastic Leukemia (T-ALL)

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1315-1315
Author(s):  
Tamara Kempter ◽  
Joachim B. Kunz ◽  
Paulina Richter-Pechanska ◽  
Katarzyna Tomska ◽  
Tobias Rausch ◽  
...  
Keyword(s):  
High Risk ◽  
Treatment Response ◽  
Board Of Directors ◽  
Tp53 Mutation ◽  
Lymphoblastic Leukemia ◽  
Initial Diagnosis ◽  
Research Support ◽  
Advisory Committees ◽  
Tp53 Mutations ◽  
First Remission

Abstract Introduction Patients who suffer a relapse of pediatric T-cell acute lymphoblastic leukemia (T-ALL) face a dismal prognosis. Prognostic molecular biomarkers that reliably predict the risk of relapse at the time of first diagnosis are not available. Inactivating mutations in TP53 were previously detected in approximately 10% of relapsed patients (Hof et al. J Clin Oncol. 2011) and are invariably associated with fatal outcome (Richter-Pechanska et al. Blood Cancer J. 2017). Mutations in other genes were identified to be either specific for relapse (NT5C2 and CCDC88A) or to be associated with a poor prognosis in relapse (IL7R, KRAS, NRAS, USP7, CNOT3 and MSH6) (Meyer et al. Nat Genet. 2013; Richter-Pechanska et al. Blood Cancer J. 2017). We hypothesized that subclones bearing such mutations can give rise to relapse and analyzed these 9 genes at initial diagnosis of T-ALL with targeted ultra-deep sequencing. Methods Leukemia samples collected at initial diagnosis of 81 children with T-ALL who later relapsed were analyzed. As a control group, we selected 79 children with T-ALL who remained in first remission for at least three years and were matched with regard to treatment response, treatment, age and sex. Targeted deep sequencing was performed by using the Agilent Haloplex High Sensitivity kit with unique molecular identifiers for reliable detection of mutations with very low allele frequencies (average read depth: 1,012x). Results Overall, we detected 75 mutations among 7 targeted genes in 33 / 81 relapsing and 21 / 79 non-relapsing patients. The average allele frequency (AF) of the identified mutations was 25% (0.8% - 83%; SD ± 18%). More than half of the variants (43/75) showed AFs below 30% and were thus classified as subclonal. Interestingly, 7 pathogenic TP53 mutations (subclonal: n=5, clonal: n=2) with AFs of 4.4% - 49.4% were exclusively discovered in 6 patients who experienced a relapse. While 2 of these patients received an allogeneic stem cell transplantation in first remission because of poor treatment response, the remaining 4 patients were treated by chemotherapy in the high-risk (n=1) or medium-risk (n=3) arm. None of the 79 non-relapsing control patients carried TP53 mutations. Consistent with the hypothesis of clonal evolution as a mechanism of relapse in T-ALL, Sanger Sequencing of the relapse sample of one TP53-positive patient confirmed that the subclone harboring the TP53 mutation A159D at initial diagnosis (AF 5.4%) expanded to a major clone (AF 42%) in relapse. The presence of TP53 mutations in two further TP53-positive patients in at least one available post-remission sample is also compatible with clonal selection. However, in a fourth patient the low allele frequency of the TP53 mutation at relapse indicates that the TP53 subclone persisted but did not expand during the development of relapse. In addition to TP53, we identified pathogenic KRAS mutations to be significantly enriched in relapsing patients (9 / 81) compared to non-relapsing patients (2 / 79) at the time of initial diagnosis (chi-squared test, p= 0.032; Table 1). Conclusion Subclonal and clonal mutations in TP53 and KRAS at initial diagnosis were enriched in T-ALL patients who later relapsed and identified approximately 17% of patients suffering a relapse. We thus propose that (subclonal) mutations of TP53 and KRAS may define a subgroup of high-risk T-ALL patients already at the time of first diagnosis. The identification of such mutations may complement the current risk stratification which depends on treatment response and may determine a new molecularly defined subgroup of T-ALLs that may benefit from intensified treatment strategies. Figure 1 Figure 1. Disclosures Schrappe: SigmaTau: Other: research support; Amgen: Other: research support; Servier: Honoraria; Novartis: Honoraria; JazzPharma: Honoraria; Servier: Honoraria, Other: research support; JazzPharma: Honoraria, Other: research support; SHIRE: Other: research support; Novartis: Honoraria, Other: research support. Cario: Novartis: Other: Lecture Fee. Muckenthaler: Silence Therapeutics: Research Funding. Kulozik: Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BioMedX: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; bluebird bio, Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Consultancy, Honoraria.

scholarly journals A Retrospective Survey among SARS-CoV-1 Infected Healthcare Workers after Three Years Post-Infection

Pathogens ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1078
Author(s):  
Szu-Wei Huang ◽  
Aspiro Nayim Urbina ◽  
Yi-Ming Arthur Chen ◽  
Sheng-Fan Wang
Keyword(s):  
Statistical Analysis ◽  
Post Infection ◽  
Neutralizing Antibodies ◽  
Healthcare Workers ◽  
Blood Samples ◽  
Retrospective Survey ◽  
Factors Affecting ◽  
Factors Associated ◽  
Neutralization Ability

Healthcare workers (HCWs) are on the frontline fighting several infectious diseases including SARS-CoV-1 and COVID-19. Coronavirus neutralizing antibodies (nAbs) were recently reported to last for a certain period. The factors affecting nAbs’ existence remain unclear. Here, we retrospectively analyzed the factors correlating with nAbs’ from SARS-CoV-1 long-term convalescence HCWs in Taiwan. One hundred and thirty SARS-CoV-1 convalescent patients were recruited between August 2006 and March 2007. Blood samples were collected to determine the anti-nucleocapsid (N) and anti-spike (S) antibodies’ existence status and neutralization ability. Neutralization ability was measured using SARS-CoV-1 pseudotyped viruses. Statistical analysis of factors associated with anti-SARS-CoV-1 antibodies’ existence status was determined using SAS software. 46.2% SARS-CoV-1 convalescent patients presented anti-N antibody after three years post-infection. Among sixty participants, ten participants co-presented anti-S antibodies. Eight participants with anti-S antibody displayed neutralization ability to SARS-CoV-1. The gender, age, and disease severity of participants did not affect the anti-N antibody existence status, whereas the anti-S antibody is significantly reduced in participants with old age (>50 years, p = 0.0434) after three years post SARS-CoV-1 infection. This study suggests that age is an important factor correlated with the duration of SARS-CoV-1 protective antibody existence status.

Sign in / Sign up

Export Citation Format

Share Document