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Among participants, 26% carried deleterious germ line variants, and 34% underwent HSCT. Deleterious germ line DDX41 variants were linked to markedly higher severe stage 3-4 acute GVHD incidence (38%) versus deleterious CHEK2 (0%), other HHM variants (12%), or no germ line variants (9%). Posttransplant cyclophosphamide reduced severe acute GVHD risk in DDX41-associated cases (0% vs 53%).",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/allogeneic-hematopoietic-stem-cell-transplant-outcomes-in-adults-with-inherited-myeloid-malignancies/378662/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/allogeneic-hematopoietic-stem-cell-transplant-outcomes-in-adults-with-inherited-myeloid-malignancies/378662.png","ImageObject",300,407,{"name":92,"@type":93},"MrHarris58","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-04","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":52},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What was the main outcome compared in this report?","Question",{"text":112,"@type":113},"The report compared posttransplant outcomes, focusing on the incidence of severe acute graft-versus-host disease (GVHD) after allogeneic HSCT.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Which germ line variants were most associated with severe acute GVHD?",{"text":117,"@type":113},"Deleterious germ line DDX41 variants were associated with a higher incidence of severe acute GVHD (stage 3-4) at 38%.",{"name":119,"@type":110,"acceptedAnswer":120},"How did posttransplant cyclophosphamide affect GVHD risk?",{"text":121,"@type":113},"Posttransplant cyclophosphamide reduced the risk of severe acute GVHD in HSCT recipients with deleterious germ line DDX41-associated myeloid neoplasms (0% vs 53%).","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},378662,1790813846,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":52,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":29,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":144},687212988360,"https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c","STIMULUS REPORT  \nAllogeneic hematopoietic stem cell transplant outcomes in adults with inherited myeloid malignancies  \nCaner Saygin, 1 Gregory Roloff, 1 Christopher N. Hahn,2-4 Rakchha Chhetri,2 Saar Gill,5 Hany Elmariah,6 Chetasi Talati,6 Emma Nunley, 1 Guimin Gao,7 Aelin Kim, 1 Michael Bishop, 1 Satyajit Kosuri, 1 Soma Das,8 Deepak Singhal,2, 9 Parvathy Venugopal,2 Claire C. Homan,2 Anna Brown,2 Hamish S. Scott,2-4 Devendra Hiwase,2,9, 10 and Lucy A. Godley 1, 8  \n1 Section of Hematology/Oncology, The University of Chicago, Chicago, IL; 2Adelaide Medical School, University of Adelaide, Adelaide, SA, Australia; 3 Department of Genetics and Molecular Pathology, SA Pathology, Adelaide, SA, Australia; 4 Centre for Cancer Biology, SA Pathology and University of South Australia, Adelaide, SA, Australia; 5 Division of Hematology-Oncology, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA; 6 Department of Blood & Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, FL; 7 Department of Public Health Sciences, The University of Chicago, Chicago, IL; 8 Department of Human Genetics, The University of Chicago, Chicago, IL; 9 Royal Adelaide Hospital, Central Adelaide Health Network, Adelaide, SA, Australia; and 10South Australian Health and Medical Research Institute, Adelaide, SA, Australia  \nKey Points  \n• Patients with deleterious germ line DDX41 variants experience higher rates of severe acute GVHD after allogeneic stem cell transplant.  \n• Posttransplant cyclophosphamide reduces GVHD rates inpatients with deleterious germ line DDX41 variants.  \nThere is increasing recognition that pathogenic germ line variants drive the development of hematopoietic cancers in many individuals. Currently, patients with hereditary hematologic malignancies (HHMs) receive similar standard therapies and hematopoietic stem cell transplant (HSCT) approaches as those with sporadic disease. We hypothesize that patients with myeloid malignancies and deleterious germ line predisposition variants have different posttransplant outcomes than those without such alleles. We studied 472 patients with myeloid neoplasms, of whom 26% had deleterious germ line variants and 34% underwent HSCT. Deleterious germ line variants in CHEK2 and DDX41 were most commonly seen in American and Australian cohorts, respectively. Patients with deleterious germ line DDX41 variants had a higher incidence of severe (stage 3-4) acute graftversus-host disease (GVHD) (38%) than recipients with deleterious CHEK2 variants (0%), other HHM variants (12%), or patients without such germ line variants (9%) (P = .002) . Importantly, the use of posttransplant cyclophosphamide reduced the risk of severe acute GVHD in patients receiving HSCT for deleterious germ line DDX41-associated myeloid neoplasms (0% vs 53%, P = .03) . Based on these results, we advocate the use of posttransplant cyclophosphamide when individuals with deleterious germ line DDX41 variants undergo allogeneic HSCT for myeloid malignancies, even when transplantation has been performed using wild-type donors.  \nIntroduction  \nRecognition of hereditary hematopoietic malignancies (HHMs) has accelerated recently, 1 with deleterious variants in >20 genes identified as myeloid and lymphoid malignancy drivers.2-4 In those with myelodysplastic syndrome, pathogenic/likely pathogenic (P/LP) germ line variants are found in 25% of pediatric patients5 and in 19% of those aged between 18 and 40 years.6 Moreover, 20% of individuals with ≥2 cancers, 1 being an HM, have a P/LP germ line variant.7 Causative genes vary across the age  \nSubmitted 23 May 2022; accepted 11 August 2022; prepublished online on Blood Advances First Edition 24 August 2022. [https://doi.org/10.1182/](https://doi.org/10.1182/)[ ](https://doi.org/10.1182/)[bloodadvances.2022008172](bloodadvances.2022008172.)[.](bloodadvances.2022008172.)  \nData are available on request from the corresponding author, Lucy A. Godley ([lgodley","cbCaisWAvb8Yw09z","https://ap.wps.com/l/cbCaisWAvb8Yw09z","pdf",265778,"English","# Key Points\n# Introduction\n## Patient Cohort and Rationale\n# Methods and Patient Characteristics\n## Table 1. Characteristics of patients who underwent allogeneic hematopoietic cell transplant","[{\"question\":\"What was the main outcome compared in this report?\",\"answer\":\"The report compared posttransplant outcomes, focusing on the incidence of severe acute graft-versus-host disease (GVHD) after allogeneic HSCT.\"},{\"question\":\"Which germ line variants were most associated with severe acute GVHD?\",\"answer\":\"Deleterious germ line DDX41 variants were associated with a higher incidence of severe acute GVHD (stage 3-4) at 38%.\"},{\"question\":\"How did posttransplant cyclophosphamide affect GVHD risk?\",\"answer\":\"Posttransplant cyclophosphamide reduced the risk of severe acute GVHD in HSCT recipients with deleterious germ line DDX41-associated myeloid neoplasms (0% vs 53%).\"}]","Allogeneic Hematopoietic Stem Cell Transplant Outcomes in Adults with Inherited Myeloid Malignancies | PDF",1790231817,15]