We here investigate the occurrence of fluoride intake-associated alterations in patients with hematologic disease on triazol antifungal medication. Clinical, laboratory, and radiology data of overall 43 patients with hematologic malignancies taking voriconazole (n ؍ 20), posaconazole (n ؍ 8), and itraconazole (n ؍ 4), and a hematologic patient control group (n ؍ 11) are described. Bone pain and radiologic evidence of periosti-
Background
Vaccines against SARS-CoV-2 have been rapidly approved. While pivotal studies were conducted in healthy volunteers, little information is available on safety and efficacy of mRNA vaccines in immunocompromised patients, including recipients of allogeneic hematopoietic cell transplantations (allo-HCT).
Objectives
Here, we used a novel assay to analyze patient- and transplant-related factors and their influence on immune responses over an extended period of time (up to 6 months) to the SARS-CoV-2 vaccination in a large and homogenous group of allo-HCT recipients at a single center in Switzerland.
Study Design
We examined longitudinal antibody responses to SARS-CoV-2 vaccination with BNT162b2 (BioNTech/Pfizer) or mRNA-1273 (Moderna) in 110 allo-HCT recipients and 86 healthy controls. Seroprofiling recording IgG, IgA, and IgM reactivities against SARS-CoV-2 antigens (receptor-binding domain (RBD), spike glycoprotein subunits S1 and S2, and nucleocapsid protein (N)) was performed prior to vaccination, prior to the 2
nd
dose, and 1, 3, and 6 months (m) after the 2
nd
dose. Patients were stratified to three groups (A) 3-6m post HCT; (B) 6-12m post HCT; and (C) >12m post HCT.
Results
Individuals early post allo-HCT (3-6 and 6-12m post HCT) developed significantly lower antibody titers after vaccination compared to patients >12m post allo-HCT and healthy controls (p<0.001). Within the cohort of HCT recipients, patients >65 years (p=0.030), those under immunosuppression for prevention or treatment of graft-vs-host disease (GVHD) (p=0.033), and/or with relapsed disease (p=0.014) displayed poor humoral immune response to the vaccine. In contrast, the intensity of the conditioning regimen, underlying disease (myeloid/lymphoid/other), and presence of chronic GVHD had no impact on antibody levels. Antibody titers achieved the highest levels 1m after the 2
nd
dose of the vaccine but substantially waned in all transplanted groups and healthy controls over time.
Conclusions
This analysis of long-term vaccine antibody response is of critical importance to allo-HCT recipients and transplant physicians to guide treatment decisions regarding re-vaccination and social behavior during the SARS-CoV-2 pandemic.
Brentuximab is a well-tolerated, promising new treatment option for advanced CTCL that can be integrated in an allogeneic stem cell transplantation plan by selectively depleting malignant CD30+ cutaneous lymphoma cells.
There are conflicting data on the role of the lectin pathway of complement activation and its recognition molecules in acute rejection and outcome after transplantation. To help resolve this we analyzed polymorphisms and serum levels of lectin pathway components in 710 consecutive kidney transplant recipients enrolled in the nationwide Swiss Transplant Cohort Study, together with all biopsy-proven rejection episodes and 1-year graft and patient survival. Functional mannose-binding lectin (MBL) levels were determined in serum samples, and previously described MBL2, ficolin 2, and MBL-associated serine protease 2 polymorphisms were genotyped. Low MBL serum levels and deficient MBL2 diplotypes were associated with a higher incidence of acute cellular rejection during the first year, in particular in recipients of deceased-donor kidneys. This association remained significant (hazard ratio 1.75, 95% confidence interval 1.18-2.60) in a Cox regression model after adjustment for relevant covariates. In contrast, there was no significant association with rates of antibodymediated rejection, patient death, early graft dysfunction or loss. Thus, results in a prospective multicenter contemporary cohort suggest that MBL2 polymorphisms result in low MBL serum levels and are associated with acute cellular rejection after kidney transplantation. Since MBL deficiency is a relatively frequent trait in the normal population, our findings may lead to individual risk stratification and customized immunosuppression.
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