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Next‐generation sequencing‐based detection of circulating tumour DNA After allogeneic stem cell transplantation for lymphoma
Author(s) -
Herrera Alex F.,
Kim Haesook T.,
Kong Katherine A.,
Faham Malek,
Sun Heather,
Sohani Aliyah R.,
Alyea Edwin P.,
Carlton Victoria E.,
Chen YiBin,
Cutler Corey S.,
Ho Vincent T.,
Koreth John,
Kotwaliwale Chitra,
Nikiforow Sarah,
Ritz Jerome,
Rodig Scott J.,
Soiffer Robert J.,
Antin Joseph H.,
Armand Philippe
Publication year - 2016
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.14311
Subject(s) - medicine , hematopoietic stem cell transplantation , hazard ratio , lymphoma , minimal residual disease , oncology , transplantation , immunology , gastroenterology , leukemia , confidence interval
Summary Next‐generation sequencing ( NGS )‐based circulating tumour DNA (ct DNA ) detection is a promising monitoring tool for lymphoid malignancies. We evaluated whether the presence of ct DNA was associated with outcome after allogeneic haematopoietic stem cell transplantation ( HSCT ) in lymphoma patients. We studied 88 patients drawn from a phase 3 clinical trial of reduced‐intensity conditioning HSCT in lymphoma. Conventional restaging and collection of peripheral blood samples occurred at pre‐specified time points before and after HSCT and were assayed for ct DNA by sequencing of the immunoglobulin or T‐cell receptor genes. Tumour clonotypes were identified in 87% of patients with adequate tumour samples. Sixteen of 19 (84%) patients with disease progression after HSCT had detectable ct DNA prior to progression at a median of 3·7 months prior to relapse/progression. Patients with detectable ct DNA 3 months after HSCT had inferior progression‐free survival ( PFS ) (2‐year PFS 58% vs. 84% in ct DNA ‐negative patients, P = 0·033). In multivariate models, detectable ct DNA was associated with increased risk of progression/death (Hazard ratio 3·9, P = 0·003) and increased risk of relapse/progression (Hazard ratio 10·8, P = 0·0006). Detectable ct DNA is associated with an increased risk of relapse/progression, but further validation studies are necessary to confirm these findings and determine the clinical utility of NGS ‐based minimal residual disease monitoring in lymphoma patients after HSCT .