| 1. |
- Baccarani, Michele, et al.
(författare)
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European LeukemiaNet recommendations for the management of chronic myeloid leukemia : 2013
- 2013
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 122:6, s. 872-884
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Forskningsöversikt (refereegranskat)abstract
- Advances in chronic myeloid leukemia treatment, particularly regarding tyrosine kinase inhibitors, mandate regular updating of concepts and management. A European LeukemiaNet expert panel reviewed prior and new studies to update recommendations made in 2009. We recommend as initial treatment imatinib, nilotinib, or dasatinib. Response is assessed with standardized real quantitative polymerase chain reaction and/or cytogenetics at 3, 6, and 12 months. BCR-ABL1 transcript levels <= 10% at 3 months, <1% at 6 months, and <= 0.1% from 12 months onward define optimal response, whereas >10% at 6 months and >1% from 12 months onward define failure, mandating a change in treatment. Similarly, partial cytogenetic response (PCyR) at 3 months and complete cytogenetic response (CCyR) from 6 months onward define optimal response, whereas no CyR (Philadelphia chromosome-positive [Ph1]>95%) at 3 months, less than PCyR at 6 months, and less than CCyR from 12 months onward define failure. Between optimal and failure, there is an intermediate warning zone requiring more frequent monitoring. Similar definitions are provided for response to second-line therapy. Specific recommendations are made for patients in the accelerated and blastic phases, and for allogeneic stem cell transplantation. Optimal responders should continue therapy indefinitely, with careful surveillance, or they can be enrolled in controlled studies of treatment discontinuation once a deeper molecular response is achieved. (Blood. 2013; 122(6):872-884)
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| 2. |
- Simonsson, Bengt, et al.
(författare)
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Interferon alpha for Treatment of Chronic Myeloid Leukemia
- 2011
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Ingår i: Current Drug Targets. - 1389-4501 .- 1873-5592. ; 12:3, s. 420-428
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Forskningsöversikt (refereegranskat)abstract
- Treatment of chronic myeloid leukemia (CML) with interferon-alpha (IFN-alpha) was introduced in the early 1980s. Several clinical trials showed a survival advantage for patients treated with IFN-alpha compared to conventional chemotherapy. Some patients achieved longstanding complete cytogenetic remissions (i.e. > 2 log tumor mass reduction). IFN-alpha was then recommended as first line medical treatment until 2001. The mechanism of this anti-leukemic effect is not clear, although IFN-alpha has many effects of potential relevance on stem cells and immunology. There is no evidence of benefit for high dose (in practice a maximally tolerated dose) compared with lower dose IFN-alpha. When IFN-alpha is combined with other drugs, we advice lower dose IFN to minimize toxicity and increase treatment adherence and duration. IFN-alpha combined with Ara-C moderately improves treatment outcome. Imatinib, a tyrosine kinase inhibitor, is now first line treatment for CML, but two large randomized studies show improved outcome when pegylated IFN-alpha is added to the treatment with imatinib. One explanation for this might be that IFN-alpha, contrary to imatinib, stimulates the quiescent stem cells to proliferate and thereby potentially increases sensitivity to imatinib. Although imatinib and other tyrosine kinase inhibitors are very efficient, they are rarely curative. IFN-alpha could be included in curatively aimed combination treatment protocols and thus still be an important element in CML treatment.
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