Is Treosulfan-Based Conditioning Attractive as a Reduced-Intensity Conditioning Regimen in Korea?

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT) was not actively performed in elderly acute myeloid leukemia (AML) or myelodysplastic syndrome patients who are at a high-risk based on hematopoietic cell transplantation-specific comorbidity index (HCT-CI). The advent of reduced-intensity conditioning (RIC) regimens has made HSCT applicable in this population. However, the selection of appropriate conditioning is a major concern for the attending physician. The benefits of combination of treosulfan and fludarabine (Treo/Flu) have been confirmed through many clinical studies. Korean data on treosulfan-based conditioning regimen are scarce. METHODS: A retrospective study was conducted to compare the clinical outcomes of allogeneic HSCT using RIC between 13 patients receiving Treo/Flu and 39 receiving busulfan/fludarabine (Bu/Flu). RESULTS: In terms of conditioning-related complications, the frequency of ≥ grade 2 nausea or vomiting was significantly lower and the duration of symptoms was shorter in the Treo/Flu group than in the Bu/Flu group. The incidence of ≥ grade 2 mucositis tended to be lower in the Treo/Flu group. In the analysis of transplant outcomes, all events of acute graft versus host disease (GVHD) and ≥ grade 2 acute GVHD occurred more frequently in the Treo/Flu group. The frequency of Epstein-Barr virus reactivation was significantly higher in the Treo/Flu group (53.8% vs. 23.1%, P = 0.037). Non-relapse mortality (NRM) at 12 months was higher in the Treo/Flu group (30.8% vs. 7.7%, P = 0.035). Significant prognostic factors included disease type, especially secondary AML, disease status and high-risk based on HCT-CI, ≥ grade 2 acute GVHD, and cases requiring ≥ 2 immunosuppressive drugs for treating acute GVHD. In the comparison of survival outcomes according to conditioning regimen, the Bu/Flu group seemed to show better results than the Treo/Flu group (60% vs. 46.2%, P = 0.092 for overall survival; 56.4% vs. 38.5%, P = 0.193 for relapse-free survival). In additional analysis for only HCT-CI high-risk groups, there was no difference in transplant outcomes except that the Treo/Flu group tended to have a higher NRM within one year after transplantation. Survival outcomes of both groups were similar. CONCLUSION: This study suggests that Treo/Flu conditioning may be an alternative to Bu/Flu regimen in elderly patients with high-risk who are not suitable for standard conditioning.

Eight-Month Follow-up After the Third Dose of BNT162b2 Vaccine in Healthcare Workers: The Question of a Fourth Dose.

BACKGROUND: A fourth dose of vaccination is known to help reduce the severity and mortality rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The South Korean vaccination guidelines for the fourth dose do not include healthcare workers (HCWs) as priority candidates. We investigated the necessity of the fourth dose in South Korean HCWs based on an 8-month follow-up period after the third vaccination. METHODS: Changes in the surrogate virus neutralization test (sVNT) inhibition (%) score were measured at one month, four months and eight months after the third vaccination. The sVNT values were analyzed between infected and uninfected groups, and their trajectories were compared. RESULTS: A total of 43 HCWs were enrolled in this study. In total, 28 cases (65.1%) were confirmed to be infected with SARS-CoV-2 (presumed omicron variant), and all had mild symptoms. Meanwhile, 22 cases (78.6%) were infected within four months of the third dose (median, 97.5 days). Eight months after the third dose, the SARS-CoV-2 (presumed omicron variant)-infected group showed significantly higher sVNT inhibition than that in the uninfected group (91.3% vs. 30.7%; P < 0.001). The antibody response due to hybrid immunity, provided by a combination of infection and vaccination, was maintained at sufficient levels for more than four months. CONCLUSION: For HCWs who had coronavirus disease 2019 infection after completing a third vaccination, a sufficient antibody response was maintained until eight months after the third dose. The recommendation of the fourth dose may not be prioritized in subjects with hybrid immunity.

Effects of Omicron Infection and Changes in Serum Antibody Response to Wild-Type, Delta, and Omicron After a Booster Dose With BNT163b2 Vaccine in Korean Healthcare Workers.

BACKGROUND: Although the primary vaccine coverage rate for coronavirus disease 2019 (COVID-19) in South Korea has exceeded 80%, the coronavirus continues to spread, with reports of a rapid decline in vaccine effectiveness. South Korea is administering booster shots despite concerns about the effectiveness of the existing vaccine. METHODS: Neutralizing antibody inhibition scores were evaluated in two cohorts after the booster dose. For the first cohort, neutralizing activity against the wild-type, delta, and omicron variants after the booster dose was evaluated. For the second cohort, we assessed the difference in neutralizing activity between the omicron infected and uninfected groups after booster vaccination. We also compared the effectiveness and adverse events (AEs) between homologous and heterologous booster doses for BNT162b2 or ChAdOx1 vaccines. RESULTS: A total of 105 healthcare workers (HCWs) that were additionally vaccinated with BNT162b2 at Soonchunhyang University Bucheon Hospital were enrolled in this study. Significantly higher surrogate virus neutralization test (sVNT) inhibition (%) was observed for the wild-type and delta variants compared to sVNT (%) for the omicron after the booster dose (97%, 98% vs. 75%; P < 0.001). No significant difference in the neutralizing antibody inhibition score was found between variants in the BNT/BNT/BNT group (n = 48) and the ChA/ChA/BNT group (n = 57). Total AEs were not significantly different between the ChA/ChA/BNT group (85.96%) and the BNT/BNT group (95.83%; P = 0.11). In the second cohort with 58 HCWs, markedly higher sVNT inhibition to omicron was observed in the omicron-infected group (95.13%) compared to the uninfected group (mean of 48.44%; P < 0.001) after four months of the booster dose. In 41 HCWs (39.0%) infected with the omicron variant, no difference in immunogenicity, AEs, or effectiveness between homogeneous and heterogeneous boosters was observed. CONCLUSION: Booster vaccination with BNT162b2 was significantly less effective for the neutralizing antibody responses to omicron variant compared to the wild-type or delta variant in healthy population. Humoral immunogenicity was sustained significantly high after 4 months of booster vaccine in the infected population after booster vaccination. Further studies are needed to understand the characteristics of immunogenicity in these populations.

Comparison of antibody response to coronavirus disease 2019 vaccination between patients with solid or hematologic cancer patients undergoing chemotherapy.

AIM: This study examined the serum antibody response of coronavirus disease 2019 (COVID-19) vaccines in solid and hematologic cancer patients undergoing chemotherapy. Levels of various inflammatory cytokines/chemokines after full vaccination were analyzed. METHODS: Forty-eight patients with solid cancer and 37 with hematologic malignancy who got fully vaccinated either with severe acute respiratory syndrome coronavirus 2 messenger RNA (mRNA) or vector vaccines or their combination were included. After consecutively collecting blood, immunogenicity was assessed by surrogate virus neutralization test (sVNT), and cytokine/chemokines were evaluated by Meso Scale Discovery assay. RESULTS: Seropositivity and protective immune response were lower in patients with hematologic cancer compared to those with solid cancers, regardless of vaccine type. Significantly lower sVNT inhibition was observed in patients with hematologic cancer (mean [SD] 45.30 [40.27] %) than in those with solid cancer (mean [SD] 61.78 [34.79] %) (p = 0.047). Heterologous vector/mRNA vaccination was independently and most markedly associated with a higher sVNT inhibition score (p < 0.05), followed by homologous mRNA vaccination. The mean serum levels of tumor necrosis factor α, macrophage inflammatory protein (MIP)-1α, and MIP-1ß were significantly higher in patients with hematologic cancers compared to those with solid cancers after the full vaccination. In 36 patients who received an additional booster shot, 29 demonstrated increased antibody titer in terms of mean sVNT (%) (40.80 and 75.21, respectively, before and after the additional dose, p < 0.001). CONCLUSION: Hematologic cancer patients receiving chemotherapy tended to respond poorly to both COVID-19 mRNA and vector vaccines and had a significantly lower antibody titer compared to those with solid cancers.

Serum Antibody Response Comparison and Adverse Reaction Analysis in Healthcare Workers Vaccinated with the BNT162b2 or ChAdOx1 COVID-19 Vaccine.

The COVID-19 pandemic is changing rapidly and requires different strategies to maintain immunization. In Korea, different COVID-19 vaccines are recommended and available for various populations, including healthcare workers (HCWs) at high risk of SARS-CoV-2 infection. We plan to evaluate the adverse events (AEs) and immunogenicity of the BNT162b2 and ChAdOx1 vaccines in HCWs at a single center. This cohort study included HCWs fully vaccinated with either BNT162b2 or ChAdOx1. Blood samples were taken eight weeks after the second vaccination with both COVID-19 vaccines and six months after the second vaccination from participants with the BNT162b2 vaccine. The primary endpoint for immunogenicity was the serum neutralizing antibody responses eight weeks after vaccination. The secondary endpoint was the incidence of various AEs within 28 days of each vaccination. Between 16 March and 23 June 2021, 115 participants were enrolled (65 in the ChAdOx1 group and 50 in the BNT162b2 group). Significantly higher surrogate virus neutralization test (sVNT) inhibition was observed in participants vaccinated with two doses of BNT162b2 (mean (SD) 91.4 (9.68)%) than in those vaccinated with ChAdOx1 (mean (SD) 73.3 (22.57)%). The effectiveness of the BNT162b2 vaccine was maintained across all age and gender categories. At six months after the second dose, serum antibody levels declined significantly in the BNT162b2 group. The main adverse events, including fever, myalgia, fatigue, and headache, were significantly higher in the ChAdOx1 group after the first dose, whereas, after the second dose, those AEs were significantly higher in the BNT162b2 group (p < 0.05). Two doses of either the ChAdOx1 or the BNT162b2 COVID-19 vaccine resulted in very high seropositivity among the HCWs at our center. The quality of the antibody response, measured by sVNT inhibition, was significantly better with the BNT162b2 vaccine than with the ChAdOx1 vaccine. There was no significant association between neutralizing antibody response and AE after each vaccination in our cohort.

NaOH-HCl neutralized urine preparation for direct testing of uropathogens by Bruker MS.

BACKGROUND: We evaluated the analytical performance of a NaOH-HCl neutralization protocol for identifying uropathogens directly from urine samples by a Bruker MS system (Bruker Daltonics, German) and sought to establish a protocol for integrating the method with conventional screening. METHODS: Among all urine samples requested for Gram staining, UF-1000i, and urine cultures by physicians, we selected samples that were positive by both Gram staining and UF-1000i testing. Urine was prepared by neutralization using 0.01M NaOH-HCl, and the samples were processed by Bruker MS. For the low detection limit, one strain each of Escherichia coli and Enterococcus faecium was inoculated in sterile deionized water and sterile urine specimens at sequential dilutions. RESULTS: In a total of 1270 urine samples, 125 samples (9.8%) were positive by both Gram staining and UF-1000i. Of 94 samples showing a single morphotype on agar plates, 82 samples had colony counts ≥105  CFU/mL and most uropathogens (95.1%, 78 of 82) had UF-1000i counts ≥106  bacteria/mL. Among them, Bruker MS correctly identified 86.6% (71/82) of all isolates, 89.2% (66/74) of Gram-negative bacteria (GNB), and 62.5% (5/8) of Gram-positive cocci (GPC) with higher average scores for GPC (mean score 2.013) and GNB (mean score 2.110). CONCLUSIONS: Bruker MS with urine preparation by NaOH-HCl neutralization provides a simple, cost-effective, and accurate method for identifying uropathogens directly from urine. Using Bruker MS when single morphotype Gram staining and the UF-1000i count as ≥106  bacteria/mL may improve the efficiency of bacterial identification in routine practice.