Post Stem Cell Transplantation Monitoring in Acute Myeloid Leukemia by Markers of Minimal Residual Disease and Engraftment
Annette S Kim, Megan K Kressin, Claudio A Mosse, Adam Seegmiller. Vanderbilt University Medical Center, Nashville, TN
Background: Despite the many prognostic markers in acute myeloid leukemia (AML), evidenced-based recommendations for monitoring minimal residual disease (MRD) in the post stem cell transplantation (SCT) setting are scarce. We sought to compare molecular and fluorescence in situ hybridization methods for assessing bone marrow engraftment (BME) and MRD to develop practice recommendations for the post-SCT patient.
Design: Retrospective data was collected and analyzed from a 12 month period beginning 8/11/2010 from adult AML patients who had received an allogeneic SCT and were monitored by subsequent bone marrow biopsies. For each case, all tandem FISH and molecular ancillary studies were analyzed and correlated with the patient's clinical status and bone marrow morphologic findings.
Results: During this 12-month span, a total of 1896 bone marrow biopsies were performed, including 122 cases of post-SCT AML with BME studies (either XY FISH or molecular short tandem repeat (STR) analysis). For the 9 cases in which both BME methods were used, the results were concordant in 89% of cases, with STR was more sensitive in the rest. In 20 cases, both FISH and molecular markers of leukemia were examined with a 75% concordance rate. In the remaining cases, the most sensitive molecular assay was the positive result. Lastly, a comparison between STR BME and FISH MRD markers conducted in 28 cases demonstrated a 68% concordance rate. STR BME was solely positive 29% of cases, and the reverse true in only 3% of cases. In fact, the STR BME could indicate as high as 59% recipient DNA by STR analysis without FISH evidence of MRD. By contrast, when STR BME and other molecular MRD studies were directly compared (25 cases), there was a 76% concordance rate, whereas STR analysis was solely positive in 16%. In each of those cases, recipient DNA was ≤3%. Finally, in 8% of cases, the molecular MRD test was more sensitive, detecting MRD below the level of sensitivity of the STR assay.
Conclusions: In summary, given the high concordance between FISH and molecular assays for BME, we recommend the STR assay due to its greater clinical sensitivity, marginally superior analytical sensitivity, and lower cost. Also, FISH MRD testing was unnecessary when a more sensitive molecular assay was available, including STR analysis which provided a better surrogate for MRD as well as measure of BME in these cases. Lastly, low levels of incomplete engraftment did not necessarily indicate molecular relapse/persistent disease associated with positivity of other molecular markers of disease.
Tuesday, March 20, 2012 9:30 AM
Poster Session III # 223, Tuesday Morning