Impact of additional cytogenetic aberrations at diagnosis on prognosis of CML: long-term observation of 1151 patients from the randomized CML Study IV

Abstract

The prognostic relevance of additional cytogenetic findings at diagnosis of chronic myeloid leukemia (CML) is unclear. The impact of additional cytogenetic findings at diagnosis on time to complete cytogenetic (CCR) and major molecular remission (MMR) and progression-free (PFS) and overall survival (OS) was analyzed using data from 1151 Philadelphia chromosome-positive (Ph ؉ ) CML patients randomized to the German CML Study IV. At diagnosis, 1003 of 1151 patients (87%) had standard t(9;22)(q34;q11) only, 69 patients (6.0%) had variant t(v;22), and 79 (6.9%) additional cytogenetic aberrations (ACAs). Of these, 38 patients (3.3%) lacked the Y chromosome (؊Y) and 41 patients (3.6%) had ACAs except ؊Y; 16 of these (1.4%) were major route (second Philadelphia [Ph] chromosome, trisomy 8, isochromosome 17q, or trisomy 19) and 25 minor route (all other) ACAs. After a median observation time of 5.3 years for patients with t(9;22), t(v;22), ؊Y, minorand major-route ACAs, the 5-year PFS was 90%, 81%, 88%, 96%, and 50%, and the 5-year OS was 92%, 87%, 91%, 96%, and 53%, respectively. In patients with major-route ACAs, the times to CCR and MMR were longer and PFS and OS were shorter (P < .001) than in patients with standard t(9;22). We conclude that major-route ACAs at diagnosis are associated with a negative impact on survival and signify progression to the accelerated phase and blast crisis. (Blood. 2011; 118(26):6760-6768)

First-line imatinib mesylate in patients with newly diagnosed accelerated phase-chronic myeloid leukemia

“…Although our cohort remains limited in size, preventing a reliable multivariate analysis, we may hypothesize that ACAs herald distinct clinical courses and varying degrees of leukemic cells responsiveness to frontline imatinib, underscoring the need for a risk stratification scheme including cytogenetic evaluations so that ACA-AP patients with poor risk at diagnosis may be offered more efficient treatments. Our hypothesis is supported by recent findings from Fabarius et al, 16 who reported that some ACAs such as Ph1 duplication, trisomy 8, isochromosome 17q and trisomy 19 had a negative impact on PFS and OS in patients treated with frontline imatinib and lacking classical hematological criteria for acceleration.…”

Additional chromosomal abnormalities in Philadelphia-positive clone: adverse prognostic influence on frontline imatinib therapy: a GIMEMA Working Party on CML analysis

“…34 These findings are partially supported by a very recent study, in which only major route ACAs were associated with a negative impact. 35 On the other hand, another observation reported that in early CP CML the presence of ACAs was one of the independent adverse predictors for PFS in the 6-months analysis and ACAs were present in 4 of the 6 patients who progressed within 1 year. 7 The European LeukemiaNet recommendations provide a warning for CP CML patients with ACAs treated frontline with imatinib, suggesting that ACAs have impact on the outcome of CML, 14 as they predict significantly for shorter PFS and OS.…”

Early molecular and cytogenetic response is predictive for long-term progression-free and overall survival in chronic myeloid leukemia (CML)

“…6 Early prediction of suboptimal response or failure would benefit this group of patients. 7 Prognostic scores to estimate patients' outcome risk at diagnosis have been established for busulfan or interferon alpha (IFN)-treated patients. 4,8,9 The new 'EUTOS Score' combining baseline spleen size and peripheral blood basophils to predict the achievement of complete cytogenetic remission (CCyR) and progression-free survival (PFS) is now available from imatinibtreated patients.…”