|Title||Impact of Conditioning Intensity and Genomics on Relapse After Allogeneic Transplantation for Patients With Myelodysplastic Syndrome.|
|Publication Type||Journal Article|
|Year of Publication||2021|
|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, H Deeg, J, Hourigan, CS|
|Journal||JCO Precis Oncol|
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.
|Alternate Journal||JCO Precis Oncol|
|PubMed Central ID||PMC8140814|
|Grant List||P30 CA008748 / CA / NCI NIH HHS / United States |
U01 HL069294 / HL / NHLBI NIH HHS / United States
U24 HL138660 / HL / NHLBI NIH HHS / United States