Prognostic value of real-time quantitative PCR (RQ-PCR) in AML with t(8;21)

Abstract

Despite the favorable prognosis of patients with acute myeloid leukemia (AML) with t(8;21)(q22;q22) translocation, relapses still occur in about 30% of the cases but no initial factors can strongly predict the risk of relapse. Several recent studies suggest that monitoring minimal residual disease (MRD) may identify patients at risk of relapse. We prospectively monitored AML1-ETO rearrangement by real-time quantitative PCR (RQ-PCR) in 21 patients uniformly treated in our center. Blood (PB) and bone marrow (BM) samples were collected during and after therapy. At diagnosis, levels of AML1-ETO transcript showed large variations and there was a trend for a higher relapse rate in patients with high pretreatment expression levels (P ¼ 0.065). After induction therapy, absolute transcript levels (below 10 À3 , compared to Kasumi cell line), or a greater than 3 log decrease by comparison to diagnosis levels, were significant predictors of the absence of relapse (P ¼ 0.02 and P ¼ 0.02, respectively). MRD levels after consolidation therapy were also significant indicators of relapse (P ¼ 10 À5 ). Comparison of BM and PB samples showed similar sensitivity for detecting AML1-ETO transcript. In conclusion, RQ-PCR appears to be an early predictive factor of the relapse risk in AML with t(8;21). PB samples can be used adequately to evaluate the level of MRD by this technique.

Clinical significance of flowcytometric minimal residual disease detection in pediatric acute myeloid leukemia patients treated according to the DCOG ANLL97/MRC AML12 protocol

“…Although MRD levels in PB do not reflect MRD levels in BM, MRD information from PB samples still may have prognostic significance. 13,[24][25][26] However, we found no prognostic significance for PB MRD at TP2 with no difference in levels between patients who remained in remission and those who relapsed (data not shown).…”

“…23 In contrast, two adult MRD studies reported comparable MRD levels between BM and PB. 24,25 The reasons for these discrepancies are not clear, but technical variance seems unlikely and differences in biology of the leukemic cells may be an explanation. Although MRD levels in PB do not reflect MRD levels in BM, MRD information from PB samples still may have prognostic significance.…”

Minimal residual disease diagnostics in myeloid malignancies in the post transplant period

“…The value of quantitative PCR for the determination of the minimal residual disease (MRD) load was confirmed in numerous previous studies, [18][19][20] and recent molecular markers such as the NPM1 mutations in AML [21][22][23] and the JAK2V617F in the CMPD [24][25][26][27] might further contribute to the spectrum of follow-up markers in the post transplant period. 6,28 Novel molecular methods-for example, on the basis of quantitative PCR-provide the opportunity of higher sensitivity for chimerism analyses.…”

“…Quantitative PCR monitoring in AML is best validated for the reciprocal gene fusions t(15;17)/PML-RARA, inv(16)/CBFB-MYH11 and t(8;21)/ AML1-ETO with sensitivities ranging from 10 À4 to 10 À6 , 20,[83][84][85] as the score of the aberrant gene expression compared after consolidation therapy and at diagnosis has a significant prognostic impact, 19 and distinct thresholds of transcript copy numbers were determined to correlate with an increased relapse risk. 84,85 The interval between the increase of the respective fusion transcripts and the clinical manifestation of relapse can be as long as 3-6 months.…”

Interactive diagnostics in the indication to allogeneic SCT in AML

“…5 The score of the aberrant gene expression compared after consolidation therapy and at diagnosis was shown to be significantly associated with survival. 124 Persistence 52 or minor decrease of transcript copy numbers 5 predicts an enhanced relapse risk. A threshold of p1% of the initial mutated cell load was determined to correlate with an increased relapse risk in patients with core binding factor leukemias 125 and in another study a transcript number of 410 during follow-up was found to correlate with significantly shortened OS in inv(16) cases.…”