Chronic Myeloid Leukemia

Published on 04/03/2015 by admin

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Chapter 27 Chronic Myeloid Leukemia

Management of the Newly Diagnosed Chronic Myeloid Leukemia Patient

What should be the initial management for CML patients? After years of clinical research, we know (a) imatinib is remarkably effective for patients treated in chronic phase, because greater than 85% of patients obtain a complete cytogenetic response and approximately 70% of cases remain in CCR at 5 years of follow-up; (b) second-generation tyrosine kinase inhibitors, dasatinib and nilotinib, used as first-line treatment for chronic phase CML may be even more effective, resulting in faster and more profound reduction in BCR-ABL levels; (c) allogeneic transplantation is generally associated with 10-year survival rates of 70% or better for younger patients in early chronic phase; and (d) outcome for patients receiving TKI treatment can be effectively monitored by sensitive RT-PCR assays.

Imatinib has become the initial treatment of choice for patients with CML. For patients diagnosed during chronic phase, imatinib is a reasonable first choice of therapy. However, in view of the association between cytogenetic and molecular responses on imatinib and survival, it is reasonable to suggest that the faster and deeper reduction in disease burden using the second-generation agents may reduce the risk for progression when compared with imatinib. The tolerability of the newer agents appears to be comparable to imatinib, although follow-up is shorter and the long-term effects of treatment are not known. It is notable that differences in overall survival have not been observed as yet. In addition, low-risk chronic-phase patients demonstrate excellent survival with imatinib. In addition, imatinib is considerably less expensive than the newer agents and a generic form will soon be available, reducing costs further. Careful monitoring of imatinib response could potentially identify the subset of patients who will benefit from second-generation tyrosine kinase inhibitor treatment. Longer-term follow-up of patients from the front-line studies and better prognostication measures for response to individual agents will be required to resolve these issues. Until then, the choice of first-line TKI is dependent on individual preference based on risk group, toxicity profile, dosing schedule, and economic factors.

For patients with chronic-phase disease, tyrosine kinase treatment can be initiated with simultaneous workup of family donors and unrelated donors. Criteria for failure or suboptimal response have been developed. Certainly, the failure of imatinib treatment to achieve a complete hematologic response at 3 months of treatment, lack of any cytogenetic response by 6 months, or lack of a major cytogenetic response by 12 months is an indication to switch therapy. By a conservative approach, patients should achieve a complete cytogenetic response by 18 months of therapy. Similarly, BCR-ABL mRNA levels greater than 10% at 6 months and greater than 1% at 12 months (using the international scale) are indicators to switch treatment. Patients who relapse after a CCR, especially those with ABL point mutations, should consider alternative therapy, including transplant. For patients diagnosed in accelerated phase or in blast crisis, initial treatment with dasatinib results in better responses than those seen with imatinib, but in general, these responses tend to be short-lived; thus advanced-phase patients should consider transplantation as soon as possible.

Figure 27-1 CHRONIC MYELOGENOUS LEUKEMIA, PERIPHERAL BLOOD TUBE, AND IMAGES OF BLOOD SMEAR AND BONE MARROW BIOPSY AND ASPIRATE IN CHRONIC PHASE.

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