The recent development of qPCR‐based chimerism assays increased dramatically the sensitivity of the method, but prospective studies on their clinical utility in relapse prediction are still lacking. We designed a prospective, non‐interventional study to compare qPCR‐based chimerism monitoring in peripheral blood (PB) or bone marrow (BM) in patients undergoing myeloablative allo‐HSCT. The study group comprised 30 patients with high risk AML, and the control group 15 patients with lymphomas. BM evaluations were performed at 6 time‐points (TPs) during the first year after HSCT, whereas PB chimerism monitoring was performed also at least at an additional TP in‐between each BM evaluation (17 total TPs). Altogether, we analyzed 409 samples (PB, n=310; BM, n=99). Pairwise comparison of PB and BM samples collected at the same TP demonstrated a moderate correlation between the two measurements (R2=0.7) with a significantly higher host chimerism in BM compared to PB (p=0.016). In the study group, 20 patients were evaluable for engraftment and 7 relapsed (median time to relapse: 73 days; range, 61‐93). The most predictive model for relapse was obtained by considering as threshold 0.13% for PB, and the value of 0.2% for BM, and by scoring as positive the cases with an increasing mixed chimerism (IMC) exceeding the threshold. Amongst the 7 study group patients who relapsed, IMC preceded relapse in PB in 4 cases (57.1%) and in BM in 2 cases (28.6%). Time from IMC to relapse was on average 17 days for PB and 33 days for BM. False positive IMC in non‐relapsed patients were 30.8% for PB and 53.8% for BM. The present study is the first to our knowledge to prospectively address qPCR‐based chimerism monitoring in high‐risk AML patients undergoing allo‐HSCT. PB resulted superior to BM for chimerism monitoring with this high‐sensitivity technique, allowing also shorter interval monitoring due to its reduced invasiveness.
QUANTITATIVE PCR-BASED CHIMERISM MONITORING IN BONE MARROW OR PERIPHERAL BLOOD TO PREDICT LEUKAEMIA RELAPSE IN HIGH-RISK PATIENTS: FINAL RESULTS OF THE KIM-PB PROSPECTIVE STUDY
Ambrosi, A;Ciceri, F;Vago, L
2018-01-01
Abstract
The recent development of qPCR‐based chimerism assays increased dramatically the sensitivity of the method, but prospective studies on their clinical utility in relapse prediction are still lacking. We designed a prospective, non‐interventional study to compare qPCR‐based chimerism monitoring in peripheral blood (PB) or bone marrow (BM) in patients undergoing myeloablative allo‐HSCT. The study group comprised 30 patients with high risk AML, and the control group 15 patients with lymphomas. BM evaluations were performed at 6 time‐points (TPs) during the first year after HSCT, whereas PB chimerism monitoring was performed also at least at an additional TP in‐between each BM evaluation (17 total TPs). Altogether, we analyzed 409 samples (PB, n=310; BM, n=99). Pairwise comparison of PB and BM samples collected at the same TP demonstrated a moderate correlation between the two measurements (R2=0.7) with a significantly higher host chimerism in BM compared to PB (p=0.016). In the study group, 20 patients were evaluable for engraftment and 7 relapsed (median time to relapse: 73 days; range, 61‐93). The most predictive model for relapse was obtained by considering as threshold 0.13% for PB, and the value of 0.2% for BM, and by scoring as positive the cases with an increasing mixed chimerism (IMC) exceeding the threshold. Amongst the 7 study group patients who relapsed, IMC preceded relapse in PB in 4 cases (57.1%) and in BM in 2 cases (28.6%). Time from IMC to relapse was on average 17 days for PB and 33 days for BM. False positive IMC in non‐relapsed patients were 30.8% for PB and 53.8% for BM. The present study is the first to our knowledge to prospectively address qPCR‐based chimerism monitoring in high‐risk AML patients undergoing allo‐HSCT. PB resulted superior to BM for chimerism monitoring with this high‐sensitivity technique, allowing also shorter interval monitoring due to its reduced invasiveness.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
