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PH+ CML Information
Ongoing Management
A key goal of treatment with Tasigna® is complete cytogenetic response (CCyR) meaning Ph+ cells can no longer be detected.1 It is important that patients be monitored for their response to Tasigna through regular blood and bone marrow tests. Testing at increasing levels of sensitivity can help determine responsiveness to treatment and presence of minimal residual disease (MRD).2
Patients may be evaluated along the following continuum of response.
- Complete Cytogenetic Response (CCyR): 0 cells contain the Ph+ chromosome2,3
- Major Cytogenetic Response (MCyR): <35 percent cells contain the Ph+ chromosome2, 3
- Major Molecular Response (MMR): Bcr-Abl/Abl ratio <0.1 percent or >3log reduction in levels of Bcr-Abl transcripts versus standardized laboratory baseline1
The most sensitive test for detecting MRD in Ph+ CML is quantitative RT-PCR (RT-qPCR), which detects the amount of Bcr-Abl mRNA transcripts.2, 3 RT-qPCR can detect a single leukemic cell in a background of 105 to 106 normal cells. RT-qPCR can be performed on peripheral blood, allowing for easier and more frequent patient evaluation than the more invasive karyotyping.2, 3 Measurement of molecular response using RT-qPCR is not yet globally standardized, so it is important that tests are repeated at the same lab to track response over time.2
It is up to you, the clinician, to decide which tests are most appropriate to monitor your patients.
Recommendations for the frequency of ongoing monitoring are shown in the table below.
Fig 2. Baccarani M, Saglio G, Goldman J, et al. Evolving concepts in the management of chronic myeloid leukemia. Recommendations from an expert panel on behalf of the European LeukemiaNet. Blood. 2006;108:1809-1820.
Table 2. Hughes T, Deininger M, Hochhaus A, et al. Monitoring CML patients responding to treatment with tyrosine kinase inhibitors: review and recommendations for harmonizing current methodology for detecting BCR-ABL transcripts and kinase domain mutations and for expressing results. Blood. 2006;108:28-37.
1. Hughes T, Branford S, Kaeda J ,et al, "Frequency of Major Molecular Responses to Imatinib or Interferon Alfa Plus Cytarabine in Newly Diagnosed Chronic Myeloid Leukemia," New Engl J Med. 2003;349:1423-1432.
2. Martinelli G, Soverini S, Iacobucci I, et al, "Monitoring Minimal Residual Disease and Controlling Drug Resistance in Chronic Myeloid Leukaemia Patients in Treatment with Imatinibas a Guide to Clinical Management," Hem Onc. 2006 (in press)).
3. Faderl S, Talpaz M, Estrov Z, et al. "The Biology of Chronic Myeloid Leukemia." N Engl J Med. 1999;341: 164-72.
