Prognosis
Goals of Therapy
The goals of therapy in CML are to achieve an optimal response as early as possible. Specifically, the immediate goal of therapy in patients with CML is to stabilise blood counts, achieve a haematological response, and, ideally, to achieve cytogenetic and molecular responses.
Table 1. Primary goals of Ph+ CML therapy: complete cytogenetic and molecular response.1,2
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A haematological response (HR) includes reducing platelet counts to < 450 × 109/L and white blood cell (WBC) counts to <10 × 109/L, decreasing the basophil level to <5%, eliminating immature granulocytes from the peripheral blood, and eradicating the signs and symptoms of disease (Table 1).3-5 Haematological improvement must be maintained for 1 month to qualify as a response.
Cytogenetic response is an important goal of therapy, with PFS benefits for patients. CyR is based on analysis of BM aspirates and the reduction or elimination of Ph+ cells. Achieving a major cytogenetic response (MCyR) (≤35% Ph+ cells) has been associated with improved survival. MCyRs are divided into complete (0% Ph+ cells) and partial (1%-35% Ph+ cells) responses. Achieving a CCyR is associated with the longest survival rate (Table 2).3,5
Molecular analytic techniques, such as FISH or RT-PCR, also may be used to detect the presence or absence of BCR-ABL and monitor disease progression.6 There is substantial evidence that major reductions in the level of BCR-ABL transcripts correlate with PFS in patients with CML who achieve a CCyR.7 For patients receiving therapy for CML, the magnitude of reduction in tumour burden is a key prognostic indicator. Moreover, most patients treated with Glivec achieve a CCyR, thus increasing the importance of molecular monitoring of residual disease to further stratify response to treatment and to promptly detect risk of loss of response.8-10 Major molecular response (MMR) has been defined as a ≥3-log decrease in BCR-ABL:BCR mRNA transcripts as measured by quantitative RT-PCR, or a BCR-ABL:ABL ratio <0.10%; Table 2).3,5 Undetectable or unquantifiable levels of BCR-ABL constitute a complete molecular response (CMR).11 The definition of response, however, is evolving based on differences in prognostic value.
References:
1. Kantarjian HM, Smith TL, O'Brien S, Beran M, Pierce S, Talpaz M. Prolonged survival in chronic myelogenous leukemia after cytogenetic response to interferon-alpha therapy. The Leukemia Service. Ann Intern Med. 1995;122:254-261.
2. Bonifazi F, de Vivo A, Rosti G, et al. Chronic myeloid leukemia and interferon-alpha: a study of complete cytogenetic responders. Blood. 2001;98:3074-3081. 3. 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.
4. Kantarjian H, Sawyers C, Hochhaus A, et al. Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia. N Engl J Med. 2002;346:645-652.
5. 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.
6. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in OncologyTM. Available at: http:/anti-infectives/Paris-Event/Live-Webcast.cfmwww.nccn.org. Accessed July 19, 2006.
7. Hughes TP, Kaeda J, Branford S, et al. Frequency of major molecular responses to imatinib or interferon alfa plus cytarabine in newly diagnosed chronic myeloid leukemia. N Engl J Med. 2003;349:1423-1432.
8. Branford S, Rudzki Z, Harper A, et al. Imatinib produces significantly superior molecular responses compared to interferon alfa plus cytarabine in patients with newly diagnosed chronic myeloid leukemia in chronic phase. Leukemia. 2003;17:2401-2409.
9. Paschka P, Muller MC, Merx K, et al. Molecular monitoring of response to imatinib (Glivec) in CML patients pretreated with interferon alpha. Low levels of residual disease are associated with continuous remission. Leukemia. 2003;17:1687-1694.
10. Rosti G, Martinelli G, Bassi S, et al. Molecular response to imatinib in late chronic phase chronic myeloid leukemia. Blood. 2004;103:2284-2290.
11. Baccarani M, Saglio G, Goldman J, et al. Evolving concepts in the management of chronic myeloid leukaemia. Recommendations from an expert panel on behalf of the European LeukaemiaNet. Blood. 2006;108:1809-1820.