{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T18:15:27Z","timestamp":1772129727972,"version":"3.50.1"},"reference-count":51,"publisher":"Springer Science and Business Media LLC","issue":"12","license":[{"start":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T00:00:00Z","timestamp":1764028800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T00:00:00Z","timestamp":1764028800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100007653","name":"Universit\u00e4tsklinikum Jena","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100007653","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Cancer Res Clin Oncol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>Complications such as graft-versus-host disease (GVHD), hepatic sinusoidal obstruction syndrome, and infections compromise the success of allogeneic hematopoietic stem cell transplantation (HSCT) as a treatment modality for malignant or genetic diseases. Identification of beneficial non-human leukocyte antigens (HLA), such as cytokines, is one approach to reduce the rate of unintended events. This study investigated the association between single-nucleotide polymorphisms (SNPs) of the gene of the proinflammatory cytokine interleukin-1 (IL-1) and treatment outcomes after allogeneic HSCT in a pediatric population.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In our single-center study, we retrospectively analyzed a cohort of 270 children and their respective donors. They underwent allogeneic HSCT for the first time, and their conditioning regimen was myeloablative in all cases. We used polymerase chain reaction to genotype the SNPs of IL-1\u03b1 rs1800587 (C\u2009&gt;\u2009T), IL-1\u03b2 rs16944 (C\u2009&gt;\u2009T), and IL-1\u03b2 rs1143627 (C\u2009&gt;\u2009T). The outcome measures included overall survival (OS), event-free survival (EFS), relapse rate (RR), transplant-related mortality (TRM), and the occurrence of acute or chronic GVHD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The distribution of IL-1\u03b1 rs1800587 genotype was as follows: we observed the CC genotype in 124 of 256 recipients (48.4%) and 132 of 270 donors (48.9%). We detected the CT genotype in 115 patients (44.9%) and 114 donors (42.2%) and found the homozygous TT genotype in 17 children (6.6%) and 24 of their donors (8.9%). The distribution of the SNP IL-1\u03b1 rs1800587 is in Hardy-Weinberg equilibrium. The incidence of moderate or severe acute GVHD was significantly decreased in recipients receiving a donor transplant with the TT genotype (4% (TT) versus 25% (CC\/CT);\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.028). We found no significant SNP IL-1\u03b1 rs1800587 (C\u2009&gt;\u2009T) associations for chronic GVHD, RR, TRM, EFS, and OS. For the other genotypes analyzed, IL-1\u03b2 rs11644 (C\u2009&gt;\u2009T) and IL-1\u03b2 rs1143627 (C\u2009&gt;\u2009T), we also found no significant associations for acute and chronic GVHD, RR, TRM, EFS, and OS, neither in donors nor in recipients. The results of the multivariate analysis revealed a hazard ratio of 0.17 (confidence interval 0.0229-1.27), and a trend that IL-1\u03b1 rs1800587 could be an independent risk factor for acute GVHD (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.084).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our study identified the donor IL-1\u03b1 rs1800587 CC\/CT genotype as a possible genetic risk factor for developing moderate to severe acute GVHD (grade II - IV) in pediatric patients who underwent allogeneic HSCT. Once confirmed in further studies, these results may influence the donor selection and prophylaxis to decrease the risk of acute GVHD in children.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00432-025-06380-x","type":"journal-article","created":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T16:13:40Z","timestamp":1764087220000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Association of donor and recipient single-nucleotide polymorphisms of interleukin-1 gene with outcomes after allogeneic hematopoietic stem cell transplantation in childhood"],"prefix":"10.1007","volume":"151","author":[{"given":"Katharina","family":"K\u00e4mpfner","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan","family":"Wittig","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernd","family":"Gruhn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,11,25]]},"reference":[{"key":"6380_CR1","doi-asserted-by":"publisher","first-page":"1504976","DOI":"10.3389\/fimmu.2025.1504976","volume":"16","author":"A Aharon","year":"2025","unstructured":"Aharon A, Avni B, Louzoun D et al (2025) MIF functional polymorphisms are associated with acute GVHD progression and steroid-refractoriness. Front Immunol 16:1504976. https:\/\/doi.org\/10.3389\/fimmu.2025.1504976","journal-title":"Front Immunol"},{"key":"6380_CR2","doi-asserted-by":"publisher","first-page":"1342","DOI":"10.1182\/blood.V84.4.1342.1342","volume":"84","author":"JH Antin","year":"1994","unstructured":"Antin JH, Weinstein HJ, Guinan EC et al (1994) Recombinant human interleukin-1 receptor antagonist in the treatment of steroid-resistant graft-versus-host disease. Blood 84:1342\u20131348","journal-title":"Blood"},{"key":"6380_CR3","doi-asserted-by":"publisher","first-page":"3479","DOI":"10.1182\/blood-2002-03-0985","volume":"100","author":"JH Antin","year":"2002","unstructured":"Antin JH, Weisdorf D, Neuberg D et al (2002) Interleukin-1 Blockade does not prevent acute graft-versus-host disease: results of a randomized, double-blind, placebo-controlled trial of interleukin-1 receptor antagonist in allogeneic bone marrow transplantation. Blood 100:3479\u20133482. https:\/\/doi.org\/10.1182\/blood-2002-03-0985","journal-title":"Blood"},{"key":"6380_CR4","doi-asserted-by":"publisher","unstructured":"Behzadi P, Sameer AS, Nissar S et al (2022) The Interleukin-1 (IL-1) Superfamily Cytokines and Their Single Nucleotide Polymorphisms (SNPs). J Immunol Res 2022:2054431. https:\/\/doi.org\/10.1155\/2022\/2054431","DOI":"10.1155\/2022\/2054431"},{"key":"6380_CR5","doi-asserted-by":"publisher","first-page":"2067","DOI":"10.2147\/OTT.S71420","volume":"7","author":"D Cheng","year":"2014","unstructured":"Cheng D, Hao Y, Zhou W (2014) IL-1alpha \u2013\u2009889\u00a0C\/T polymorphism and cancer susceptibility: a meta-analysis. Onco Targets Ther 7:2067\u20132074. https:\/\/doi.org\/10.2147\/OTT.S71420","journal-title":"Onco Targets Ther"},{"key":"6380_CR6","doi-asserted-by":"publisher","first-page":"807","DOI":"10.1046\/j.1365-2141.2001.02811.x","volume":"113","author":"H Cullup","year":"2001","unstructured":"Cullup H, Dickinson AM, Jackson GH, Taylor PR, Cavet J, Middleton PG (2001) Donor Interleukin 1 receptor antagonist genotype associated with acute graft-versus-host disease in human leucocyte antigen-matched sibling allogeneic transplants. Br J Haematol 113:807\u2013813. https:\/\/doi.org\/10.1046\/j.1365-2141.2001.02811.x","journal-title":"Br J Haematol"},{"key":"6380_CR7","doi-asserted-by":"publisher","first-page":"778","DOI":"10.1046\/j.1365-2141.2003.04510.x","volume":"122","author":"H Cullup","year":"2003","unstructured":"Cullup H, Dickinson AM, Cavet J, Jackson GH, Middleton PG (2003) Polymorphisms of interleukin-1alpha constitute independent risk factors for chronic graft-versus-host disease after allogeneic bone marrow transplantation. Br J Haematol 122:778\u2013787. https:\/\/doi.org\/10.1046\/j.1365-2141.2003.04510.x","journal-title":"Br J Haematol"},{"key":"6380_CR8","doi-asserted-by":"publisher","first-page":"154788","DOI":"10.1016\/j.cyto.2019.154788","volume":"123","author":"GAV da Silva","year":"2019","unstructured":"da Silva GAV, de Mesquita TGR, de Souza Encarnacao HV et al (2019) A polymorphism in the IL1B gene (rs16944 T\/C) is associated with cutaneous leishmaniasis caused by leishmania Guyanensis and plasma cytokine Interleukin receptor antagonist. Cytokine 123:154788. https:\/\/doi.org\/10.1016\/j.cyto.2019.154788","journal-title":"Cytokine"},{"key":"6380_CR9","doi-asserted-by":"publisher","first-page":"3155","DOI":"10.1182\/blood-2016-12-754994","volume":"129","author":"CEM de Mooij","year":"2017","unstructured":"de Mooij CEM, Netea MG, van der Velden W, Blijlevens NMA (2017) Targeting the interleukin-1 pathway in patients with hematological disorders. Blood 129:3155\u20133164. https:\/\/doi.org\/10.1182\/blood-2016-12-754994","journal-title":"Blood"},{"key":"6380_CR49","doi-asserted-by":"publisher","unstructured":"Deng JS, Qin P, Li XX, Du YH (2013) Association between interleukin-1beta C (3953\/4)T polymorphism and chronic periodontitis: evidence from a meta-analysis. Hum Immunol 74:371\u2013378. https:\/\/doi.org\/10.1016\/j.humimm.2012.11.018","DOI":"10.1016\/j.humimm.2012.11.018"},{"key":"6380_CR10","doi-asserted-by":"publisher","first-page":"906","DOI":"10.1038\/ni.3503","volume":"17","author":"NC Di Paolo","year":"2016","unstructured":"Di Paolo NC, Shayakhmetov DM (2016) Interleukin 1alpha and the inflammatory process. Nat Immunol 17:906\u2013913. https:\/\/doi.org\/10.1038\/ni.3503","journal-title":"Nat Immunol"},{"key":"6380_CR11","doi-asserted-by":"publisher","first-page":"1266","DOI":"10.1016\/s0198-8859(01)00324-x","volume":"62","author":"AM Dickinson","year":"2001","unstructured":"Dickinson AM, Cavet J, Cullup H, Wang XN, Sviland L, Middleton PG (2001) GvHD risk assessment in hematopoietic stem cell transplantation: role of cytokine gene polymorphisms and an in vitro human skin explant model. Hum Immunol 62:1266\u20131276. https:\/\/doi.org\/10.1016\/s0198-8859(01)00324-x","journal-title":"Hum Immunol"},{"key":"6380_CR12","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1146\/annurev.immunol.021908.132612","volume":"27","author":"CA Dinarello","year":"2009","unstructured":"Dinarello CA (2009) Immunological and inflammatory functions of the interleukin-1 family. Annu Rev Immunol 27:519\u2013550. https:\/\/doi.org\/10.1146\/annurev.immunol.021908.132612","journal-title":"Annu Rev Immunol"},{"key":"6380_CR13","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1111\/imr.12621","volume":"281","author":"CA Dinarello","year":"2018","unstructured":"Dinarello CA (2018) Overview of the IL-1 family in innate inflammation and acquired immunity. Immunol Rev 281:8\u201327. https:\/\/doi.org\/10.1111\/imr.12621","journal-title":"Immunol Rev"},{"key":"6380_CR14","doi-asserted-by":"publisher","first-page":"480","DOI":"10.1212\/wnl.55.4.480","volume":"55","author":"Y Du","year":"2000","unstructured":"Du Y, Dodel RC, Eastwood BJ et al (2000) Association of an Interleukin 1 alpha polymorphism with alzheimer\u2019s disease. Neurology 55:480\u2013483. https:\/\/doi.org\/10.1212\/wnl.55.4.480","journal-title":"Neurology"},{"key":"6380_CR15","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1097\/MPH.0b013e3182427575","volume":"34","author":"L Elbahlawan","year":"2012","unstructured":"Elbahlawan L, McArthur J, Quasney MW, Pei D, Srivastava K, Dahmer MK, Barfield R (2012) Association of IL-1beta \u2013\u2009511 polymorphism with severe veno-occlusive disease in pediatric-matched allogeneic hematopoietic stem cell transplantation. J Pediatr Hematol Oncol 34:175\u2013179. https:\/\/doi.org\/10.1097\/MPH.0b013e3182427575","journal-title":"J Pediatr Hematol Oncol"},{"key":"6380_CR16","doi-asserted-by":"publisher","first-page":"e26229","DOI":"10.1371\/journal.pone.0026229","volume":"6","author":"JL Espinoza","year":"2011","unstructured":"Espinoza JL, Takami A, Nakata K et al (2011a) A genetic variant in the IL-17 promoter is functionally associated with acute graft-versus-host disease after unrelated bone marrow transplantation. PLoS ONE 6:e26229. https:\/\/doi.org\/10.1371\/journal.pone.0026229","journal-title":"PLoS ONE"},{"key":"6380_CR17","doi-asserted-by":"publisher","first-page":"1455","DOI":"10.1038\/bmt.2010.325","volume":"46","author":"JL Espinoza","year":"2011","unstructured":"Espinoza JL, Takami A, Onizuka M et al (2011b) A single nucleotide polymorphism of IL-17 gene in the recipient is associated with acute GVHD after HLA-matched unrelated BMT. Bone Marrow Transpl 46:1455\u20131463. https:\/\/doi.org\/10.1038\/bmt.2010.325","journal-title":"Bone Marrow Transpl"},{"key":"6380_CR18","doi-asserted-by":"publisher","first-page":"945","DOI":"10.1016\/j.bbmt.2005.09.004","volume":"11","author":"AH Filipovich","year":"2005","unstructured":"Filipovich AH, Weisdorf D, Pavletic S et al (2005) National institutes of health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transpl 11:945\u2013956. https:\/\/doi.org\/10.1016\/j.bbmt.2005.09.004","journal-title":"Biol Blood Marrow Transpl"},{"key":"6380_CR19","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1080\/01621459.1999.10474144","volume":"94","author":"JP Fine","year":"1999","unstructured":"Fine JP, Gray RJ (1999) A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc 94:496\u2013509","journal-title":"J Am Stat Assoc"},{"key":"6380_CR20","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1097\/00007890-197410000-00001","volume":"18","author":"H Glucksberg","year":"1974","unstructured":"Glucksberg H, Storb R, Fefer A et al (1974) Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors. Transplantation 18:295\u2013304. https:\/\/doi.org\/10.1097\/00007890-197410000-00001","journal-title":"Transplantation"},{"key":"6380_CR21","doi-asserted-by":"publisher","first-page":"1141","DOI":"10.1214\/aos\/1176350951","volume":"16","author":"RJ Gray","year":"1988","unstructured":"Gray RJ (1988) A class of K-Sample tests for comparing the cumulative incidence of a competing risk. Annals Stat 16:1141\u20131154","journal-title":"Annals Stat"},{"key":"6380_CR22","doi-asserted-by":"publisher","first-page":"1571","DOI":"10.1016\/j.bbmt.2009.08.001","volume":"15","author":"B Gruhn","year":"2009","unstructured":"Gruhn B, Intek J, Pfaffendorf N et al (2009) Polymorphism of interleukin-23 receptor gene but not of NOD2\/CARD15 is associated with graft-versus-host disease after hematopoietic stem cell transplantation in children. Biol Blood Marrow Transpl 15:1571\u20131577. https:\/\/doi.org\/10.1016\/j.bbmt.2009.08.001","journal-title":"Biol Blood Marrow Transpl"},{"key":"6380_CR23","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1016\/j.bbmt.2015.09.001","volume":"22","author":"AC Harris","year":"2016","unstructured":"Harris AC, Young R, Devine S et al (2016) International, multicenter standardization of acute Graft-versus-Host disease clinical data collection: A report from the Mount Sinai acute GVHD international consortium. Biol Blood Marrow Transpl 22:4\u201310. https:\/\/doi.org\/10.1016\/j.bbmt.2015.09.001","journal-title":"Biol Blood Marrow Transpl"},{"key":"6380_CR24","doi-asserted-by":"publisher","first-page":"e0204914","DOI":"10.1371\/journal.pone.0204914","volume":"13","author":"S Hierlmeier","year":"2018","unstructured":"Hierlmeier S, Eyrich M, Wolfl M, Schlegel PG, Wiegering V (2018) Early and late complications following hematopoietic stem cell transplantation in pediatric patients - A retrospective analysis over 11 years. PLoS ONE 13:e0204914. https:\/\/doi.org\/10.1371\/journal.pone.0204914","journal-title":"PLoS ONE"},{"key":"6380_CR25","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1182\/blood-2003-10-3543","volume":"104","author":"E Holler","year":"2004","unstructured":"Holler E, Rogler G, Herfarth H et al (2004) Both donor and recipient NOD2\/CARD15 mutations associate with transplant-related mortality and GvHD following allogeneic stem cell transplantation. Blood 104:889\u2013894. https:\/\/doi.org\/10.1182\/blood-2003-10-3543","journal-title":"Blood"},{"key":"6380_CR26","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1016\/j.bbmt.2014.12.001","volume":"21","author":"MH Jagasia","year":"2015","unstructured":"Jagasia MH, Greinix HT, Arora M et al (2015) National institutes of health consensus development project on criteria for clinical trials in chronic Graft-versus-Host disease: I. The 2014 diagnosis and staging working group report. Biol Blood Marrow Transpl 21:389\u2013401e381. https:\/\/doi.org\/10.1016\/j.bbmt.2014.12.001","journal-title":"Biol Blood Marrow Transpl"},{"key":"6380_CR27","doi-asserted-by":"publisher","first-page":"1899","DOI":"10.1084\/jem.20130084","volume":"210","author":"D Jankovic","year":"2013","unstructured":"Jankovic D, Ganesan J, Bscheider M et al (2013) The Nlrp3 inflammasome regulates acute graft-versus-host disease. J Exp Med 210:1899\u20131910. https:\/\/doi.org\/10.1084\/jem.20130084","journal-title":"J Exp Med"},{"key":"6380_CR28","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1111\/imr.12620","volume":"281","author":"K Khazim","year":"2018","unstructured":"Khazim K, Azulay EE, Kristal B, Cohen I (2018) Interleukin 1 gene polymorphism and susceptibility to disease. Immunol Rev 281:40\u201356. https:\/\/doi.org\/10.1111\/imr.12620","journal-title":"Immunol Rev"},{"key":"6380_CR29","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1016\/j.jtct.2021.03.033","volume":"27","author":"CL Kitko","year":"2021","unstructured":"Kitko CL, Pidala J, Schoemans HM et al (2021) National institutes of health consensus development project on criteria for clinical trials in chronic Graft-versus-Host disease: IIa. The 2020 clinical implementation and early diagnosis working group report. Transpl Cell Ther 27:545\u2013557. https:\/\/doi.org\/10.1016\/j.jtct.2021.03.033","journal-title":"Transpl Cell Ther"},{"key":"6380_CR50","doi-asserted-by":"publisher","unstructured":"Kiyohara C, Horiuchi T, Takayama K, Nakanishi Y (2010) IL1B rs1143634 polymorphism, cigarette smoking, alcohol use, and lung cancer risk in a Japanese population. J Thorac Oncol 5:299\u2013304. https:\/\/doi.org\/10.1097\/JTO.0b013e3181c8cae3","DOI":"10.1097\/JTO.0b013e3181c8cae3"},{"key":"6380_CR30","doi-asserted-by":"publisher","unstructured":"Landvik NE, Tekpli X, Anmarkrud KH, Haugen A, Zienolddiny S (2012) Molecular characterization of a cancer-related single nucleotide polymorphism in the pro-inflammatory interleukin-1B gene. Mol Carcinog 51 Suppl 1E168\u2013175. https:\/\/doi.org\/10.1002\/mc.21910","DOI":"10.1002\/mc.21910"},{"key":"6380_CR31","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1046\/j.1365-2141.2003.04314.x","volume":"121","author":"ML MacMillan","year":"2003","unstructured":"MacMillan ML, Radloff GA, DeFor TE, Weisdorf DJ, Davies SM (2003) Interleukin-1 genotype and outcome of unrelated donor bone marrow transplantation. Br J Haematol 121:597\u2013604. https:\/\/doi.org\/10.1046\/j.1365-2141.2003.04314.x","journal-title":"Br J Haematol"},{"key":"6380_CR32","doi-asserted-by":"publisher","first-page":"626","DOI":"10.1097\/00007890-199609150-00015","volume":"62","author":"PL McCarthy Jr","year":"1996","unstructured":"McCarthy PL Jr., Williams L, Harris-Bacile M et al (1996) A clinical phase I\/II study of Recombinant human interleukin-1 receptor in glucocorticoid-resistant graft-versus-host disease. Transplantation 62:626\u2013631. https:\/\/doi.org\/10.1097\/00007890-199609150-00015","journal-title":"Transplantation"},{"key":"6380_CR33","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1111\/j.1365-2141.2007.06552.x","volume":"137","author":"PA Mehta","year":"2007","unstructured":"Mehta PA, Eapen M, Klein JP et al (2007) Interleukin-1 alpha genotype and outcome of unrelated donor Haematopoietic stem cell transplantation for chronic myeloid leukaemia. Br J Haematol 137:152\u2013157. https:\/\/doi.org\/10.1111\/j.1365-2141.2007.06552.x","journal-title":"Br J Haematol"},{"key":"6380_CR34","doi-asserted-by":"publisher","first-page":"3625","DOI":"10.1182\/blood-2009-09-243840","volume":"115","author":"Y Nguyen","year":"2010","unstructured":"Nguyen Y, Al-Lehibi A, Gorbe E et al (2010) Insufficient evidence for association of NOD2\/CARD15 or other inflammatory bowel disease-associated markers on GVHD incidence or other adverse outcomes in T-replete, unrelated donor transplantation. Blood 115:3625\u20133631. https:\/\/doi.org\/10.1182\/blood-2009-09-243840","journal-title":"Blood"},{"key":"6380_CR35","doi-asserted-by":"publisher","first-page":"718","DOI":"10.1006\/geno.2002.6751","volume":"79","author":"MJ Nicklin","year":"2002","unstructured":"Nicklin MJ, Barton JL, Nguyen M, FitzGerald MG, Duff GW, Kornman K (2002) A sequence-based map of the nine genes of the human interleukin-1 cluster. Genomics 79:718\u2013725. https:\/\/doi.org\/10.1006\/geno.2002.6751","journal-title":"Genomics"},{"key":"6380_CR36","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1002\/1531-8249(200003)47:3<365::AID-ANA13>3.0.CO;2-G","volume":"47","author":"JA Nicoll","year":"2000","unstructured":"Nicoll JA, Mrak RE, Graham DI et al (2000) Association of interleukin-1 gene polymorphisms with alzheimer\u2019s disease. Ann Neurol 47:365\u2013368","journal-title":"Ann Neurol"},{"key":"6380_CR37","doi-asserted-by":"publisher","first-page":"4861","DOI":"10.1007\/s11033-013-2585-4","volume":"40","author":"MR Noori-Daloii","year":"2013","unstructured":"Noori-Daloii MR, Jalilian N, Izadi P, Sobhani M, Rabii-Gilani Z, Yekaninejad MS (2013) Cytokine gene polymorphism and graft-versus-host disease: a survey in Iranian bone marrow transplanted patients. Mol Biol Rep 40:4861\u20134867. https:\/\/doi.org\/10.1007\/s11033-013-2585-4","journal-title":"Mol Biol Rep"},{"key":"6380_CR38","doi-asserted-by":"publisher","first-page":"1557","DOI":"10.1086\/315889","volume":"182","author":"RC Read","year":"2000","unstructured":"Read RC, Camp NJ, di Giovine FS et al (2000) An interleukin-1 genotype is associated with fatal outcome of meningococcal disease. J Infect Dis 182:1557\u20131560. https:\/\/doi.org\/10.1086\/315889","journal-title":"J Infect Dis"},{"key":"6380_CR39","doi-asserted-by":"publisher","first-page":"3355","DOI":"10.4049\/jimmunol.1400983","volume":"193","author":"K Reinhardt","year":"2014","unstructured":"Reinhardt K, Foell D, Vogl T et al (2014) Monocyte-induced development of Th17 cells and the release of S100 proteins are involved in the pathogenesis of graft-versus-host disease. J Immunol 193:3355\u20133365. https:\/\/doi.org\/10.4049\/jimmunol.1400983","journal-title":"J Immunol"},{"key":"6380_CR40","doi-asserted-by":"publisher","first-page":"1395","DOI":"10.4049\/jimmunol.1601342","volume":"198","author":"P Rider","year":"2017","unstructured":"Rider P, Voronov E, Dinarello CA, Apte RN, Cohen I (2017) Alarmins: feel the stress. J Immunol 198:1395\u20131402. https:\/\/doi.org\/10.4049\/jimmunol.1601342","journal-title":"J Immunol"},{"key":"6380_CR41","doi-asserted-by":"publisher","first-page":"1703","DOI":"10.1182\/blood-2014-12-567834","volume":"125","author":"S Sarantopoulos","year":"2015","unstructured":"Sarantopoulos S, Ritz J (2015) Aberrant B-cell homeostasis in chronic GVHD. Blood 125:1703\u20131707. https:\/\/doi.org\/10.1182\/blood-2014-12-567834","journal-title":"Blood"},{"key":"6380_CR42","doi-asserted-by":"publisher","first-page":"648","DOI":"10.1038\/nm.3517","volume":"20","author":"L Schwab","year":"2014","unstructured":"Schwab L, Goroncy L, Palaniyandi S et al (2014) Neutrophil granulocytes recruited upon translocation of intestinal bacteria enhance graft-versus-host disease via tissue damage. Nat Med 20:648\u2013654. https:\/\/doi.org\/10.1038\/nm.3517","journal-title":"Nat Med"},{"key":"6380_CR43","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1038\/sj.bmt.1705727","volume":"40","author":"L Scrucca","year":"2007","unstructured":"Scrucca L, Santucci A, Aversa F (2007) Competing risk analysis using R: an easy guide for clinicians. Bone Marrow Transpl 40:381\u2013387. https:\/\/doi.org\/10.1038\/sj.bmt.1705727","journal-title":"Bone Marrow Transpl"},{"key":"6380_CR44","doi-asserted-by":"publisher","first-page":"1388","DOI":"10.1038\/bmt.2009.359","volume":"45","author":"L Scrucca","year":"2010","unstructured":"Scrucca L, Santucci A, Aversa F (2010) Regression modeling of competing risk using R: an in depth guide for clinicians. Bone Marrow Transpl 45:1388\u20131395. https:\/\/doi.org\/10.1038\/bmt.2009.359","journal-title":"Bone Marrow Transpl"},{"key":"6380_CR51","doi-asserted-by":"publisher","unstructured":"Smith AJ, Humphries SE (2009) Cytokine and cytokine receptor gene polymorphisms and their functionality. Cytokine Growth Factor Rev 20:43\u201359. https:\/\/doi.org\/10.1016\/j.cytogfr.2008.11.006","DOI":"10.1016\/j.cytogfr.2008.11.006"},{"key":"6380_CR45","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1182\/blood-2014-01-514752","volume":"124","author":"G Socie","year":"2014","unstructured":"Socie G, Ritz J (2014) Current issues in chronic graft-versus-host disease. Blood 124:374\u2013384. https:\/\/doi.org\/10.1182\/blood-2014-01-514752","journal-title":"Blood"},{"key":"6380_CR46","doi-asserted-by":"publisher","first-page":"2435","DOI":"10.1182\/blood-2014-07-590232","volume":"125","author":"A Varelias","year":"2015","unstructured":"Varelias A, Gartlan KH, Kreijveld E et al (2015) Lung parenchyma-derived IL-6 promotes IL-17A-dependent acute lung injury after allogeneic stem cell transplantation. Blood 125:2435\u20132444. https:\/\/doi.org\/10.1182\/blood-2014-07-590232","journal-title":"Blood"},{"key":"6380_CR47","doi-asserted-by":"publisher","first-page":"2434","DOI":"10.1073\/pnas.0308705101","volume":"101","author":"A Werman","year":"2004","unstructured":"Werman A, Werman-Venkert R, White R et al (2004) The precursor form of IL-1alpha is an intracrine Proinflammatory activator of transcription. Proc Natl Acad Sci U S A 101:2434\u20132439. https:\/\/doi.org\/10.1073\/pnas.0308705101","journal-title":"Proc Natl Acad Sci U S A"},{"key":"6380_CR48","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1182\/blood.2019004271","volume":"136","author":"R Zeiser","year":"2020","unstructured":"Zeiser R (2020) Introduction to a review series on pathophysiology and treatment of acute GVHD. Blood 136:375\u2013376. https:\/\/doi.org\/10.1182\/blood.2019004271","journal-title":"Blood"}],"container-title":["Journal of Cancer Research and Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00432-025-06380-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00432-025-06380-x\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00432-025-06380-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T19:39:10Z","timestamp":1765654750000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00432-025-06380-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,25]]},"references-count":51,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["6380"],"URL":"https:\/\/doi.org\/10.1007\/s00432-025-06380-x","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-7696683\/v1","asserted-by":"object"}]},"ISSN":["1432-1335"],"issn-type":[{"value":"1432-1335","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,25]]},"assertion":[{"value":"23 September 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 November 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 November 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no potential conflicts of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"All procedures were in accordance with the ethical standards of the institutional research committee. The study was conducted in accordance with the 1964 Declaration of Helsinki and its subsequent amendments, or with comparable ethical standards. The study was approved by the Ethics Committee of the Jena University Hospital (2021\u20132084). All patients and\/or their parents or legal guardians gave written informed consent.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}],"article-number":"331"}}