title: Predictive value of clonality assays in patients with non-Hodgkin's lymphoma undergoing autologous bone marrow transplant: a single institution study.
abstract: Recent studies have documented an increased risk of therapy-related myelodysplastic syndrome or acute myelogenous leukemia (t-MDS/AML) after autologous bone marrow transplant (ABMT) for non-Hodgkin's lymphoma (NHL). To develop methods to identify patients at risk for this complication, we have investigated the predictive value of clonal bone marrow (BM) hematopoiesis for the development of t-MDS/AML, as defined by an X-inactivation based clonality assay at the human androgen receptor locus (HUMARA), in a group of patients undergoing ABMT for NHL from a single institution (Dana-Farber Cancer Institute, Boston, MA). One hundred four female patients were analyzed. At the time of ABMT, the prevalence of polyclonal hematopoiesis was 77% (80/104), of skewed X-inactivation pattern (XIP) was 20% (21/104), and of clonal hematopoiesis was 3% (3/104). To determine the predictive value of clonality for the development of t-MDS/AML, a subgroup of 78 patients with at least 18 months follow-up was analyzed. As defined by the HUMARA assay, 53 of 78 patients had persistent polyclonal hematopoiesis, 15 of 78 had skewed XIP, and 10 of 78 (13.5%) either had clonal hematopoiesis at the time of ABMT or developed clonal hematopoiesis after ABMT. t-MDS/AML developed in 2 of 53 patients with polyclonal hematopoiesis and in 4 of 10 with clonal hematopoiesis. We conclude that a significant proportion of patients have clonal hematopoiesis at the time of ABMT and that clonal hematopoiesis, as detected by the HUMARA assay, is predictive of the development of t-MDS/AML (P = .004).
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Brigham and Women's Hospital, the Dana-Farber Cancer Institute, and the Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 021115, USA.
authors.forename: S
authors.initials: S
authors.lastname: Mach-Pascual
authors.forename: R D
authors.initials: RD
authors.lastname: Legare
authors.forename: D
authors.initials: D
authors.lastname: Lu
authors.forename: M
authors.initials: M
authors.lastname: Kroon
authors.forename: D
authors.initials: D
authors.lastname: Neuberg
authors.forename: R
authors.initials: R
authors.lastname: Tantravahi
authors.forename: R M
authors.initials: RM
authors.lastname: Stone
authors.forename: A S
authors.initials: AS
authors.lastname: Freedman
authors.forename: L M
authors.initials: LM
authors.lastname: Nadler
authors.forename: J G
authors.initials: JG
authors.lastname: Gribben
authors.forename: D G
authors.initials: DG
authors.lastname: Gilliland
mesh_terms: D000328:Adult; D002454:Cell Differentiation; D005260:Female; D006085:Graft Survival; D006410:Hematopoiesis; D019650:Hematopoietic Stem Cell Mobilization; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000473:pathology*; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000473:pathology* / Q000628:therapy*; D008875:Middle Aged; D011237:Predictive Value of Tests; D014182:Transplantation, Autologous