Allogeneic Hematopoietic Stem Cell Transplant Outcomes in Adults with Inherited Myeloid Malignancies

Autor: 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, Lucy A. Godley
Přispěvatelé: Saygin, Caner, Roloff, Gregory, Hahn, Christopher N, Chhetri, Rakchha, Gill, Saar, Elmariah, Hany, Talati, Chetasi, Nunley, Emma, Gao, Guimin, Kim, Aelin, Bishop, Michael, Kosuri, Satyajit, Das, Soma, Singhal, Deepak, Venugopal, Parvathy, Homan, Claire C, Brown, Anna, Scott, Hamish S, Hiwase, Devendra, Godley, Lucy A
Rok vydání: 2022
Předmět:
Zdroj: Blood. 140:10542-10544
ISSN: 1528-0020
0006-4971
DOI: 10.1182/blood-2022-167098
Popis: There 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 graft-versus-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.
Databáze: OpenAIRE
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