Impact of Conditioning Intensity and Genomics on Relapse After Allogeneic Transplantation for Patients With Myelodysplastic Syndrome.

Journal Article (Journal Article)

PURPOSE: Patients with myelodysplastic syndrome (MDS) are at risk of relapse after allogeneic hematopoietic cell transplantation. The utility of ultra-deep genomic testing to predict and the impact of conditioning intensity to prevent MDS relapse are unknown. METHODS: Targeted error-corrected DNA sequencing was performed on preconditioning blood samples from patients with MDS (n = 48) from the Blood and Marrow Transplant Clinical Trials Network 0901 phase III randomized clinical trial, which compared outcomes by allogeneic hematopoietic cell transplantation conditioning intensity in adult patients with < 5% marrow myeloblasts and no leukemic myeloblasts in blood on morphological analysis at the time of pretransplant assessment. Clinical end points (53-month median follow-up) included transplant-related mortality (TRM), relapse, relapse-free survival (RFS), and overall survival (OS). Of the 48 patients examined, 14 experienced TRM, 23 are relapse-free, and 11 relapsed, of which 7 died. RESULTS: Using a previously described set of 10 gene regions, 42% of patients (n = 20) had mutations detectable before random assignment to reduced intensity conditioning (RIC) or myeloablative conditioning (MAC). Testing positive was associated with increased rates of relapse (3-year relapse, 40% v 11%; P = .022) and decreased OS (3-year OS, 55% v 79%, P = .045). In those testing positive, relapse rates were higher (3-year relapse, 75% v 17%; P = .003) and RFS was lower (3-year RFS, 13% v 49%; P = .003) in RIC versus MAC arms. Testing additional genes, including those associated with MDS, did not improve prognostication. CONCLUSION: This study provides evidence that targeted DNA sequencing in patients with MDS before transplant can identify those with highest post-transplant relapse rates. In those testing positive, random assignment to MAC lowered but did not eliminate relapse risk.

Full Text

Duke Authors

Cited Authors

  • Dillon, LW; Gui, G; Logan, BR; Fei, M; Ghannam, J; Li, Y; Licon, A; Alyea, EP; Bashey, A; Devine, SM; Fernandez, HF; Giralt, S; Hamadani, M; Howard, A; Maziarz, RT; Porter, DL; Warlick, ED; Pasquini, MC; Scott, BL; Horwitz, ME; Deeg, HJ; Hourigan, CS

Published Date

  • 2021

Published In

Volume / Issue

  • 5 /

PubMed ID

  • 34036237

Pubmed Central ID

  • PMC8140814

Electronic International Standard Serial Number (EISSN)

  • 2473-4284

Digital Object Identifier (DOI)

  • 10.1200/PO.20.00355

Language

  • eng

Conference Location

  • United States