Serial and quantitative analysis of mixed hematopoietic chimerism by PCR in patients with acute leukemias allows the prediction of relapse after allogeneic BMT

Within a prospective study we analyzed hematopoietic chimerism in serial peripheral blood samples taken from 55 patients with acute leukemias (ALL 21, AML 20, MDS 14) with a median age of 13.5 years at very short time intervals following allogeneic bone marrow transplantation (allo-BMT), The investigation was performed to determine the implications of mixed hematopoietic chimerism (MC) with regard to the clinical outcome in patients with acute leukemias after allo-BMT, Analysis of chimerism was performed by PCR of variable number of tandem repeat (VNTR) sequences with a maximum sensitivity of 0.8%, Thirteen male patients transplanted with the marrow of a female donor were also studied by amplification of a Y-chromosome-specific alphoid repeat (0.1-0.01% sensitivity), VNTR analysis in 55 patients revealed complete chimerism (CC) in 36 cases, MC in 18 follow-ups and autologous recovery in one patient, Quantitative analysis of MC identified 10/18 patients with increasing autologous patterns in whom 9/10 subsequently relapsed, The patient with autologous recovery relapsed as well, Eight of 18 patients with MC showed decreasing amounts of autologous DNA and became CC upon further follow-up, In contrast, only 7/36 patients with CC in the prior analysis of chimerism status relapsed, However, in 4/7 patients the interval between last CC confirmation and relapse was more than 4 months, In 2/7 patients autologous DNA was not detectable in peripheral blood but in bone marrow aspirates, One of these seven patients developed a fulminant relapse within 3 weeks, The probability of relapse-free survival for patients with CC is 0.67 (It = 36), for patients with decreasing MC 1.0 (n = 8) and for patients with increasing MC 0.1 (n = 10), In summary, the results demonstrate that serial and quantitative chimerism analysis at short time intervals by PCR provides a reliable and rapid screening method for the early detection of recurrence of underlying disease and is therefore a prognostic tool to identify patients at highest risk of relapse.