Molecular monitoring of response to imatinib (Glivec®) in CML patients pretreated with interferon alpha. Low levels of residual disease are associated with continuous remission
A significant proportion of chronic myeloid leukemia (CML) patients achieve a major cytogenetic remission (MCR) to imatinib therapy after failing interferon (IFN) α-based protocols. We sought to determine levels of residual disease in patients with MCR using various molecular methods and to establis...
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| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
10 September 2003
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| In: |
Leukemia
Year: 2003, Volume: 17, Issue: 9, Pages: 1687-1694 |
| ISSN: | 1476-5551 |
| DOI: | 10.1038/sj.leu.2403033 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/sj.leu.2403033 Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/2403033 
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| Author Notes: | P. Paschka, M.C. Müller, K. Merx, S. Kreil, C. Schoch, T. Lahaye, A. Weisser, A. Petzold, H. König, U. Berger, H. Gschaidmeier, R. Hehlmann and A. Hochhaus |
| Summary: | A significant proportion of chronic myeloid leukemia (CML) patients achieve a major cytogenetic remission (MCR) to imatinib therapy after failing interferon (IFN) α-based protocols. We sought to determine levels of residual disease in patients with MCR using various molecular methods and to establish a relation between residual BCR-ABL transcript levels and rate of relapse in complete cytogenetic remission (CCR). Response was measured by conventional cytogenetic analysis, hypermetaphase and interphase fluorescence in situ hybridization (HM-FISH, IP-FISH) of bone marrow (BM) cells, qualitative nested and quantitative reverse transcriptase polymerase chain reaction (RT-PCR) for BCR-ABL transcripts. We investigated 323 peripheral blood (PB) and BM samples from 48 CML patients who achieved a complete (Ph+ 0%; n=41) or partial (Ph+ 1-34%; n=7) cytogenetic remission after 3-20 months of imatinib therapy. Prior to imatinib, 35 patients were in chronic phase (CP), eight in accelerated phase (AP), four in myeloid and one in lymphoid blast crisis. HM-FISH results correlated with ratios BCR-ABL/ABL in PB and BM. In patients with CCR, residual disease was detectable by HM-FISH (31%), IP-FISH (18%), and RT-PCR (100%). During follow-up, BCR-ABL became undetectable in two patients (one CP, one AP) by both nested and quantitative RT-PCR. CCR is ongoing in 30 evaluable patients, 11 patients have relapsed. At the time of best response, median ratios BCR-ABL/ABL were 2.1% (range 0.82-7.8) in patients with subsequent relapse and 0.075% (range 0-3.9) in patients with ongoing remission (P=0.0011). All 16 CP patients, who achieved ratios BCR-ABL/ABL <0.1% as best molecular response are in continuous remission, while 6/13 patients (46%) with ratios ⩾0.1% have relapsed (P=0.0036). We conclude that: (i) in patients with CCR to imatinib, HM-FISH and RT-PCR usually reveal residual BCR-ABL+ cells; (ii) RT-PCR results derived from PB and BM are comparable in CP CML; and (iii) low levels of residual disease with ratios BCR-ABL/ABL <0.1% are associated with continuous remission. |
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| Item Description: | Gesehen am 16.05.2022 |
| Physical Description: | Online Resource |
| ISSN: | 1476-5551 |
| DOI: | 10.1038/sj.leu.2403033 |