Assessment of residual disease in acute leukemia by means of polymerase chain reaction

Along a 5-year period in a single institution, specific molecular markers w ere prospectively looked for in consecutive patients with acute leukemia, b y means of polymerase chain reaction (PCR): In patients with acute lymphobl astic leukemia (ALL), the BCR/ABL and TEL-AML1 fusion transcripts as well a s clonotypic immunoglobulin gene rearrangements were investigated, whereas in patients with acute myelogenous leukemia (AML) the PML-RAR alpha, AML1-E TO and CBF beta-MYH11 fusion proteins were assessed. Specific molecular mar kers were identified in 15/ 75 patients: Four with ALL (three with clonotyp ic IgG rearrangements and one with BCR/ABL) and 11 with AML (nine with the PML/RAR alpha fusion protein - M3 AML -, and two with the AML1/ETO fusion,p rotein - M2 AML -). During follow-up periods ranging from 1 to 60 months, s even patients cleared the residual disease assessed by PCR (RD-PCR), wherea s eight patients had either persistence of RD-PCR or a molecular relapse. F or patients without or with RD-PCR, the 30-month survival (SV) was 86% and 14%, respectively, whereas median SV was > 60 and two months, also respecti vely (p < 0.01). Six of eight patients with detectable RD-PCR died, all of them within three months after the detection of the RD-PGR, whereas two of the patients that relapsed were rescued with treatment and entered a second molecular remission. Two of the three molecular relapses were detected wit hout an overt morphological relapse, it is concluded that PCR is a valuable method for assessing residual disease and that early diagnosis of relapses may lead into effective salvage treatment in some instances.