DETECTION OF MINIMAL RESIDUAL DISEASE BY POLYMERASE CHAIN-REACTION INB-CELL MALIGNANCIES

It was the aim of this study to examine the prognostic value of the de tection of minimal residual disease (MRD), with the help of the polyme rase chain reaction (PCR), in patients with non-Hodgkin's lymphoma (NH L) and multiple myeloma (MM) who underwent sequential high-dose therap y with peripheral blood progenitor cell (PBPC) support, and in patient s with acute myeloid leukemia (AML) of the subclass M4Eo who underwent high-dose consolidation therapy. Basis for the application of a PCR a ssay disease entities are the following specific gene rearrangements: the t(14;18) translocation in a high percentage of NHL, the clonal rea rrangement of the Ig heavy chain locus resulting in a unique complemen tary determining region 3 (CDR3) for MM region and the inversion 16 ch aracteristic for the M4Eo subclass of AML, Before the G-CSF supported cytotoxic chemotherapy was given, 65% of the 52 patients with low- and intermediate-grade NHL enrolled into the study had PCR(+) bone marrow (BM) and/or peripheral blood (PB) samples, The majority of patients ( 29 of 52) were autografted with a PCR(+) transplant, The proportion of harvests containing t(14;18)t cells was two-fold less in patients mob ilized in first remission than in those with a history of previous tre atment failure, This was also reflected when examining the B cell cont ents of the harvests measured as CD19(+) cells with a 3.3-fold smaller proportion of CD19(+) cells in leukapheresis (LP) products of patient s mobilized in first remission. Patients who received a PCR(-) transpl ant are in remission and remained PCR(-) in BM and PB samples post-tra nsplantation, Conversion to PCR-negativity in BM and PB samples post-t ransplantation was observed in 11 of 19 patients who were also in remi ssion, In contrast, 6 of 29 patients who were autografted with PCR(+) products relapsed, while 4 of them presented with PCR(-) samples on se veral occasions post-trans plantation. In patients with MM, the assess ment of MRD in PBPC harvests was based on the CDR3 regions of the Ig h eavy chain locus as a marker for clonality, The great majority of LP p roducts (17 out of 19) contained tumor cells, To prove positive enrich ment procedures for the elimination of tumor cells, CD34(+) and CD19() cell fractions obtained from LP samples in an experimental setting v ia preparative flow cytometry were analyzed for MRD resulting in PCR-n egativity for all CD34(+) fractions, The results of the four patients with AML M4Eo and inversion 16 are preliminary, with a tendency of per sistence of PCR-positivity after finishing the high-dose consolidation therapy, In one case, recurrence of disease was accompanied by an inc rease of the signal strength in the PCR assay, Longer follow-up period s are necessary to determine the prognostic value of these PCR finding s in the different disease entities.