Molecular heterogeneity in complete cytogenetic responders after interferon-α therapy for chronic myelogenous leukemia : low levels of minimal residual disease are associated with continuing remission

• Published in: Blood 2000, Vol.95 (1), p.62-66
• Main Authors: HOCHHAUS, A, REITER, A, HEHLMANN, R, GOLDMAN, J. M, CROSS, N. C. P, SAUSSELE, S, REICHERT, A, EMIG, M, KAEDA, J, SCHULTHEIS, B, BERGER, U, SHEPHERD, P. C. A, ALLAN, N. C
• Format: Article
• Language: English
• Subjects: Antineoplastic agents; Biological and medical sciences; Immunotherapy; Medical sciences; Pharmacology. Drug treatments
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.v95.1.62

A substantial minority of patients with chronic myelogenous leukemia (CML) achieve a complete response (CR) to treatment with interferon- (IFN), defined as the disappearance of Philadelphia chromosome-positive metaphases. Currently it is unclear how long IFN treatment should be continued for such patients. We used a competitive reverse transcriptase-polymerase chain reaction (RT-PCR) to quantify levels of BCR-ABL transcripts in 297 peripheral blood specimens collected from 54 patients who had achieved CR with IFN. The median duration of observation was 1.9 years (range, 0.3-11.0 years). Total ABL transcripts were quantified as internal control and results were expressed as the ratio BCR-ABL/ABL. All 54 patients had molecular evidence of residual disease, although 3 patients were intermittently PCR negative. The median BCR-ABL/ABL ratio at the time of maximal response for each patient was 0.045% (range, 0%-3.6%). During the period of observation 14 patients relapsed, 11 cytogenetically to chronic phase disease and 3 directly to blastic phase. The median ratio of BCR-ABL/ABL at maximal response was significantly higher in patients who relapsed than in those who remained in CR (0.49% versus 0.021%,P