0
selected
-
1.
Decreased Plasma Level of Cytokeratin 20 (KRT20) Is Indicative of the Emergence and Severity of Acute GvHD Irrespective to the Type of Organ Involvement
Lupsa, N., Szegedi, Á, Gézsi, A., Vuncs, Z., Masszi, T., Mikala, G., Reményi, P., Deola, S., Lakshmanan, A. P., Terranegra, A., et al
Biomedicines. 2022;10(3)
Abstract
Accurate risk prediction of acute graft versus host disease (aGvHD) is currently an unmet clinical need. This study sought to analyze whether three plasma proteins expressed in a largely skin- and gut-restricted manner would be affected by the development of acute cutaneous and gastrointestinal aGvHD. The diagnostic sensitivity, specificity, and prognostic value of plasma cytokeratin-15 (KRT15) cytokeratin-20 (KRT20), and occludin (OCLN) were evaluated in a discovery and a validation cohort using ELISA in comparison with elafin (PI3) and regenerating family member 3 alpha (REG3A), two established markers of skin- and gut aGvHD. The discovery cohort (n = 39) revealed that at the time of diagnosis, plasma KRT20 showed a progressive decrease from unaffected individuals to patients with single-, and patients with multi-organ aGvHD. KRT20 was affected by cutaneous (p = 0.0263) and gastrointestinal aGvHD (p = 0.0242) independently and in an additive manner. Sensitivity and specificity of KRT20 for aGvHD involving both target organs (AUC = 0.852) were comparable to that of PI3 for skin-aGvHD (AUC = 0.708) or that of REG3A for gut-aGvHD (AUC = 0.855). Patient follow-up in the validation cohort (n = 67) corroborated these observations (p < 0.001), and linked low KRT20 to grade 2+ disease (p < 0.001), but failed to confirm low KRT20 as an independent risk factor. These data established a link between low plasma KRT20 levels and moderate to severe aGvHD involving multiple target organs.
-
2.
Investigation of TGFB1 -1347C>T variant as a biomarker after allogeneic hematopoietic stem cell transplantation
Kovy, P., Meggyesi, N., Varga, L., Balassa, K., Bors, A., Gopcsa, L., Paksi, M., Batai, A., Vad, E., Sinko, J., et al
Bone marrow transplantation. 2019
Abstract
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative therapeutic option for malignant hematopoietic diseases. Cytokines including transforming growth factor beta1 (TGFbeta1) play a pivotal role in immune reconstruction, and the development of graft versus host disease (GvHD) or infections. The aim of this study was to investigate the role of TGFB1 gene -1347C>T variant in the outcome of HSCT in a cohort of 409 adult recipient-donor pairs. TGFB1 variant was analysed from genomic DNA with LightCycler hybridisation probe method. In case of myeloablative conditioning, donor TGFB1 genotype correlated with overall survival (60-month OS for CC: 62.1 +/- 4.8%; CT: 46.8 +/- 4.8%; TT: 35.6 +/- 9.3%; p = 0.032), which was independent of age, donor type and GvHD prophylaxis in multivariate analysis (HR:2.35, 95%CI:1.35-4.10, p = 0.003). The cumulative incidence of acute GvHD grade III-IV [CC:10%; CT:17%; TT:24%], and non-relapse mortality was higher in TT-carriers (24-month NRM: CC:24%; CT:26%; TT:46%, p = 0.035). We did not find any association between recipient TGFB1 -1347C>T polymorphism and HSCT outcome. Our results suggest that donor TGFB1 -1347C>T may exert an adverse influence on the outcome of myeloablative conditioning transplantation.
-
3.
Impact of extramedullary disease in patients with newly diagnosed multiple myeloma undergoing autologous stem cell transplantation: A study from the Chronic Malignancies Working Party of the EBMT
Gagelmann, N., Eikema, D. J., Iacobelli, S., Koster, L., Nahi, H., Stoppa, A. M., Masszi, T., Caillot, D., Lenhoff, S., Udvardy, M., et al
Haematologica. 2018
Abstract
We investigated extramedullary disease in newly diagnosed multiple myeloma patients and its impact on outcome following first line autologous stem cell transplantation. We identified 3744 adult myeloma patients who received upfront single (n = 3391) or tandem transplantation (n = 353) between 2005 and 2014 with available data on extramedullary in-volvement at diagnosis. The overall incidence of extramedullary disease was 18.2% (n = 682) and increased per year from 6.5% (2005) to 23.7% (2014). Paraskeletal involvement was found in 543 (14.5%) and extramedullary organ involvement in 139 (3.7%) while the majority of 3062 (81.8%) patients had no extramedullary disease. More patients with extramedul-lary organ involvement had multiple involved sites (≥2;) (p < 0.001). In patients with single sites compared to patients without the disease, upfront transplantation resulted in at least similar 3-year progression-free survival (paraskeletal: p = 0.86, and extramedullary organ: p = 0.88). In single paraskeletal involvement, this translated less clearly into 3-year overall survival (p = 0.07) while single organ involvement was significantly worse (p = 0.001). Multiple organ sites were associated with worse outcome (p < 0.001 and p = 0.01). First line treatment with tandem compared with single transplantation resulted in similar survival in patients with extramedullary disease at diagnosis (p = 0.13, respectively).
-
4.
Sex-specific survival difference in association with HLA-DRB1*04 following allogeneic haematopoietic stem cell transplantation for lymphoid malignancies
Balassa, K., Andrikovics, H., Remenyi, P., Batai, A., Szilvasi, A., Bors, A., Kiss, K. P., Rajczy, K., Inotai, D., Torbagyi, E., et al
Human Immunology. 2017
Abstract
The role of HLA system in allogeneic haematopoietic stem cell transplantation (allo-HSCT) outcome is unarguable. In this study we investigated association of HLA-A,-B and-DRB1 alleles with overall survival (OS) in 186 patients undergoing allo-HSCT for lymphoid malignancies. Analyses confirmed significantly better OS for HLA-DRB1*04 carriers compared with non-carriers (p=0.01). Survival benefit was confined to male patients (in multivariate analyses p=0.034, hazard ratio 0.35, 95% confidence interval 0.13-0.92), whereas in females no difference was noted (p=0.82). Furthermore, donor gender also affected outcome and transplantation from female HLA-DRB1*04 carrier donors resulted in superior survival compared with female non-carrier donors (p=0.01). Combined analyses including recipient/donor gender and HLA-DRB1*04 showed that survival of male patients varied significantly according to donor gender and HLA-DRB1*04 carriership (p=0.04) with best survival among HLA-DRB1*04 carriers transplanted from female donors. Of relevance to our results, HLA-DRB1*04 has been documented as risk allele group for lymphoid malignancies, and studies described a male-specific risk. We believe that our findings provide further supporting evidence for sex-specific alterations secondary to HLA-DRB1*04 or related genes. Further studies are warranted to evaluate whether in contrast to general favour of male donors HLA-DRB1*04 carrier patients with lymphoid malignancies could benefit from transplantation from female donors. Copyright © 2017 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.