Molecular monitoring of response to imatinib (Glivec®) in CML patients pretreated with interferon alpha. Low levels of residual disease are associated with continuous remission

• Verfasst von: Paschka, Peter [VerfasserIn]
• Verfasst von: Müller, Martin Christian [VerfasserIn]
• Verfasst von: Merx, Kirsten [VerfasserIn]
• Verfasst von: Kreil, Sebastian [VerfasserIn]
• Verfasst von: Schoch, C. [VerfasserIn]
• Verfasst von: Lahaye, T. [VerfasserIn]
• Verfasst von: Weißer, Andreas [VerfasserIn]
• Verfasst von: Petzold, A. [VerfasserIn]
• Verfasst von: König, H. [VerfasserIn]
• Verfasst von: Berger, Ute [VerfasserIn]
• Verfasst von: Gschaidmeier, Harald [VerfasserIn]
• Verfasst von: Hehlmann, Rüdiger [VerfasserIn]
• Verfasst von: Hochhaus, Andreas [VerfasserIn]
• Titel: Molecular monitoring of response to imatinib (Glivec®) in CML patients pretreated with interferon alpha. Low levels of residual disease are associated with continuous remission
• Verf.angabe: 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
• E-Jahr: 2003
• Jahr: 10 September 2003
• Umfang: 8 S.
• Fussnoten: Gesehen am 16.05.2022
• Titel Quelle: Enthalten in: Leukemia
• Ort Quelle: London : Springer Nature, 1997
• Jahr Quelle: 2003
• Band/Heft Quelle: 17(2003), 9, Seite 1687-1694
• ISSN Quelle: 1476-5551
• DOI: doi:10.1038/sj.leu.2403033
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Cancer Research
• Sach-SW: general
• Sach-SW: Hematology
• Sach-SW: Intensive / Critical Care Medicine
• Sach-SW: Internal Medicine
• Sach-SW: Medicine/Public Health
• Sach-SW: Oncology
• K10plus-PPN: 180183556X

Abstract

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.