Predictive Value of Clonality Assays in Patients With Non-Hodgkin's Lymphoma Undergoing Autologous Bone Marrow Transplant: A Single Institution Study

• Published in: Blood 1998-06, Vol.91 (12), p.4496-4503
• Main Authors: Mach-Pascual, Sara, Legare, Robert D., Lu, Doanh, Kroon, Mary, Neuberg, Donna, Tantravahi, Ramana, Stone, Richard M., Freedman, Arnold S., Nadler, Lee M., Gribben, John G., Gilliland, D. Gary
• Format: Article
• Language: English
• Subjects: Adult; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Biological and medical sciences; Bone marrow, stem cells transplantation. Graft versus host reaction; Cell Differentiation; Female; Graft Survival; Hematopoiesis; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells - pathology; Humans; Lymphoma, Non-Hodgkin - pathology; Lymphoma, Non-Hodgkin - therapy; Medical sciences; Middle Aged; Predictive Value of Tests; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Transplantation, Autologous
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V91.12.4496

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).