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Predictive Value of Clonality Assays in Patients With Non-Hodgkin's
Lymphoma Undergoing Autologous Bone Marrow Transplant: A Single
Institution Study
Sara Mach-Pascual,
Robert D. Legare,
Doanh Lu,
Mary Kroon,
Donna Neuberg,
Ramana Tantravahi,
Richard M. Stone,
Arnold S. Freedman,
Lee M. Nadler,
John G. Gribben, and
D. Gary Gilliland
From the 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.
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).
Blood, Vol. 91 No. 12 (June 15), 1998:
pp. 4496-4503
© 1998 by The American Society of Hematology.
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