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

TitleImpact of Conditioning Intensity and Genomics on Relapse After Allogeneic Transplantation for Patients With Myelodysplastic Syndrome.
Publication TypeJournal Article
Year of Publication2021
AuthorsDillon, 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, H Deeg, J, Hourigan, CS
JournalJCO Precis Oncol
Volume5
Date Published2021
ISSN2473-4284
Abstract

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

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% 11%; = .022) and decreased OS (3-year OS, 55% 79%, = .045). In those testing positive, relapse rates were higher (3-year relapse, 75% 17%; = .003) and RFS was lower (3-year RFS, 13% 49%; = .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.

DOI10.1200/PO.20.00355
Alternate JournalJCO Precis Oncol
PubMed ID34036237
PubMed Central IDPMC8140814
Grant ListP30 CA008748 / CA / NCI NIH HHS / United States
U01 HL069294 / HL / NHLBI NIH HHS / United States
U24 HL138660 / HL / NHLBI NIH HHS / United States