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https://hdl.handle.net/2440/137747
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Type: | Journal article |
Title: | Allogeneic hematopoietic stem cell transplant outcomes in adults with inherited myeloid malignancies |
Author: | Saygin, C. Roloff, G.W. Hahn, C.N. Chhetri, R. Gill, S.I. Elmariah, H. Talati, C. Nunley, E. Gao, G. Kim, A. Bishop, M.R. Kosuri, S. Das, S. Singhal, D. Venugopal, P. Homan, C.C. Brown, A.L. Scott, H.S. Hiwase, D.K. Godley, L.A. |
Citation: | Blood Advances, 2023; 7(4):549-554 |
Publisher: | American Society of Hematology |
Issue Date: | 2023 |
ISSN: | 2473-9529 2473-9537 |
Statement of Responsibility: | Caner Saygin, Gregory Roloff, Christopher N. Hahn, Rakchha Chhetri, Saar Gill, Hany Elmariah, Chetasi Talati, Emma Nunley, Guimin Gao, Aelin Kim, Michael Bishop, Satyajit Kosuri, Soma Das, Deepak Singhal, Parvathy Venugopal, Claire C. Homan, Anna Brown, Hamish S. Scott, Devendra Hiwase, and Lucy A. Godley |
Abstract: | There is increasing recognition that pathogenic germline 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 germline predisposition variants have different post-transplant outcomes compared to those without such alleles. We studied 472 patients with myeloid neoplasms, of whom 26% had deleterious germline variants (DGVs) and 34% underwent HSCT. DGVs in CHEK2 and DDX41 were most commonly seen in American and Australian cohorts, respectively. Patients with deleterious germline DDX41 variants had a higher incidence of severe (stage 3-4) acute graft versus host disease (GVHD) (38%) compared to recipients with deleterious CHEK2 variants (0%), other HHM variants (12%), or patients without such germline variants (9%) (p= 0.002). Importantly, the use of post-transplant cyclophosphamide reduced the risk of severe acute GVHD in patients receiving HSCT for deleterious germline DDX41-associated myeloid neoplasms (0% vs 53%, p=0.03). Based on these results, we advocate the use of post-transplant cyclophosphamide when individuals with deleterious germline DDX41 variants undergo allogeneic HSCT for myeloid malignancies, even when transplantation has been performed using wild-type donors. |
Keywords: | Hematologic Neoplasms |
Description: | Final version published online 17 February 2023 |
Rights: | © 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved. |
DOI: | 10.1182/bloodadvances.2022008172 |
Published version: | http://dx.doi.org/10.1182/bloodadvances.2022008172 |
Appears in Collections: | Medicine publications |
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hdl_137747.pdf | Published version | 262.42 kB | Adobe PDF | View/Open |
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