Incomplete Engraftment Is Not Equivalent to Residual Disease: A Two-Year Study of Hematological Malignancies
Delecia R LaFrance, Cindy Vnencak-Jones, Claudio A Mosse, Adam Seegmiller, Annette S Kim. Vanderbilt University Medical Center, Nashville, TN
Background: Evaluating minimal residual disease for hematologic malignancies after allogeneic stem cell transplantation (post-SCT) is complicated by the scarcity of evidence-based recommendations for test selection and interpretation. In an effort to explore the relationship between donor stem-cell engraftment and the presence of disease, we compare bone marrow engraftment (BME) and minimal residual disease (MRD) results from post-SCT patients with a spectrum of hematologic malignancies.
Design: We retrospectively reviewed all bone marrow biopsies collected for adult patients with hematologic malignancies post-SCT from 8/2010 through 2/2012, with additional follow-up until 8/2012, and categorized the data by diagnostic entity. For each case, bone marrow histology, molecular/FISH/flow cytometry MRD results, and BME studies (short tandem repeat [STR] analysis) were compared.
Results: Of the 2764 bone marrow biopsies examined over the two-year period, we identified 341 post-SCT cases: 183 myelodysplastic syndrome/acute myeloid leukemia (MDS/AML), 47 precursor lymphoblastic leukemia (ALL), 37 non-Hodgkin lymphoma (NHL), 35 myeloproliferative neoplasm (MPN), 15 plasma cell myeloma, and 22 other. Taken together, MRD and BME studies were concordant in 56.3% of cases studied (169/300). In 38% of cases (112/292), STR studies identified recipient DNA while MRD studies were negative, a trend evident across the spectrum of hematologic malignancies studied. In fact, in the absence of residual disease, recipient DNA approached as high as 59% for ALL (mean 7.1%), 62% for MDS/AML (mean 6.2%), and 64% for NHL (mean 10.3%). Conversely, in only 5% of cases (15/292) was residual disease detected in the presence of complete engraftment with exceedingly low levels of disease detected in all cases; this was most evident in Philadelphia chromosome positive ALL where BCR/ABL levels were around 0.01%.
Conclusions: BME and MRD studies enumerate separate qualities in the post transplant patient, and should not be interpreted as surrogates for each other. In one-third of cases, there can be significant incomplete engraftment (recipient DNA up to 64%) without any morphologic or molecular evidence of disease, a scenario observed across all hematologic malignancies in this cohort. This data demonstrates that minor variations in BME should not be equated with relapsing disease and that low level MRD can be detected when less sensitive BME studies are negative.
Wednesday, March 6, 2013 9:30 AM
Poster Session V # 243, Wednesday Morning