Contributions
Type: Oral Presentation
Presentation during EHA20: From 14.06.2015 08:30 to 14.06.2015 08:45
Location: Room Strauss 1
Background
Major route additional cytogenetic aberrations (ACA) at diagnosis of chronic myeloid leukemia (CML) indicate an increased risk of progression and shorter survival. Since all major route ACA are unbalanced it is unclear whether other unbalanced ACA at diagnosis also confer an unfavourable prognosis.
Aims
Since major route ACA are unbalanced aberrations and since patients with minor route ACA may also progress, the question arose whether a more generally defined group of chromosomal abnormalities such as unbalanced aberrations rather than only the specific major route ACA indicate progression.
Methods
On the basis of 1348 Philadelphia (Ph) chromosome positive chronic phase patients of the randomized CML-study IV we examined the impact of unbalanced minor route ACA at diagnosis in comparison to major route ACA on prognosis.
Cytogenetic analyses of at least 20 Giemsa(G)-banded or Reverse(R)-banded bone marrow metaphases at diagnosis were interpreted according to the International System for Human Cytogenetic Nomenclature (2013). Patients with cytogenetic aberrations in Ph-negative clones at diagnosis were excluded from this analysis. Patients with constitutional changes were assigned to the group with standard translocation t(9;22)(q34;q11) or variant translocation t(v;22). In patients showing a complex aberrant karyotype G- or R-banding analysis was combined with m-FISH analysis. Cytogenetic remission was defined according to the ELN recommendations.
Progression-free survival (PFS) was defined as the time from diagnosis until the beginning of accelerated phase, blast crisis, or death from any cause whatever event came first. For overall survival (OS), death from any cause was the only event. Probabilities of PFS and OS were calculated by the Kaplan-Meier method and compared by the log-rank test. Patients were censored at the date of last follow-up. P-values lower than 5% were considered significant. Due to the explorative character of this work, no adjustment of p-values was done and all p-values have to be interpreted descriptively.
Results
At diagnosis, 1175 patients (87%) had a translocation t(9;22)(q34;q11) and 74 (5.5%) a variant translocation t(v;22) only, while a loss of the Y-chromosome (-Y) was present in addition in 44 (3.3%), balanced or unbalanced minor route ACA each in 17 (1.3% each) cases and major route ACA in 21 (1.6%) cases.
Patients with unbalanced minor route ACA achieved complete cytogenetic remission, major molecular remission, PFS and OS at similar rates as did patients with t(9;22), t(v;22), -Y, and balanced minor route karyotypes. In contrast, patients with major route ACA had a shorter OS and PFS than all other groups (p<0.005 for all pairwise comparisons with major route). Five year survival probabilities were for t(9;22): 91.4% (95% CI 89.5 – 93.1), t(v; 22): 87% (77.2 – 94.3), - Y: 89.0% (76.7 – 97.0), balanced: 100%, unbalanced minor route: 92.3% (72.4 – 100), major route: 52.2% (28.2 – 75.5).
Summary
We conclude that only major route, but not unbalanced minor route ACA at diagnosis have a negative impact on prognosis of CML. This observation may be of relevance also to other cancers.
Keyword(s): Chronic myeloid leukemia, Cytogenetics, Outcome, Prognosis
Session topic: CML: Molecular-cytogenetic diagnostics
Type: Oral Presentation
Presentation during EHA20: From 14.06.2015 08:30 to 14.06.2015 08:45
Location: Room Strauss 1
Background
Major route additional cytogenetic aberrations (ACA) at diagnosis of chronic myeloid leukemia (CML) indicate an increased risk of progression and shorter survival. Since all major route ACA are unbalanced it is unclear whether other unbalanced ACA at diagnosis also confer an unfavourable prognosis.
Aims
Since major route ACA are unbalanced aberrations and since patients with minor route ACA may also progress, the question arose whether a more generally defined group of chromosomal abnormalities such as unbalanced aberrations rather than only the specific major route ACA indicate progression.
Methods
On the basis of 1348 Philadelphia (Ph) chromosome positive chronic phase patients of the randomized CML-study IV we examined the impact of unbalanced minor route ACA at diagnosis in comparison to major route ACA on prognosis.
Cytogenetic analyses of at least 20 Giemsa(G)-banded or Reverse(R)-banded bone marrow metaphases at diagnosis were interpreted according to the International System for Human Cytogenetic Nomenclature (2013). Patients with cytogenetic aberrations in Ph-negative clones at diagnosis were excluded from this analysis. Patients with constitutional changes were assigned to the group with standard translocation t(9;22)(q34;q11) or variant translocation t(v;22). In patients showing a complex aberrant karyotype G- or R-banding analysis was combined with m-FISH analysis. Cytogenetic remission was defined according to the ELN recommendations.
Progression-free survival (PFS) was defined as the time from diagnosis until the beginning of accelerated phase, blast crisis, or death from any cause whatever event came first. For overall survival (OS), death from any cause was the only event. Probabilities of PFS and OS were calculated by the Kaplan-Meier method and compared by the log-rank test. Patients were censored at the date of last follow-up. P-values lower than 5% were considered significant. Due to the explorative character of this work, no adjustment of p-values was done and all p-values have to be interpreted descriptively.
Results
At diagnosis, 1175 patients (87%) had a translocation t(9;22)(q34;q11) and 74 (5.5%) a variant translocation t(v;22) only, while a loss of the Y-chromosome (-Y) was present in addition in 44 (3.3%), balanced or unbalanced minor route ACA each in 17 (1.3% each) cases and major route ACA in 21 (1.6%) cases.
Patients with unbalanced minor route ACA achieved complete cytogenetic remission, major molecular remission, PFS and OS at similar rates as did patients with t(9;22), t(v;22), -Y, and balanced minor route karyotypes. In contrast, patients with major route ACA had a shorter OS and PFS than all other groups (p<0.005 for all pairwise comparisons with major route). Five year survival probabilities were for t(9;22): 91.4% (95% CI 89.5 – 93.1), t(v; 22): 87% (77.2 – 94.3), - Y: 89.0% (76.7 – 97.0), balanced: 100%, unbalanced minor route: 92.3% (72.4 – 100), major route: 52.2% (28.2 – 75.5).
Summary
We conclude that only major route, but not unbalanced minor route ACA at diagnosis have a negative impact on prognosis of CML. This observation may be of relevance also to other cancers.
Keyword(s): Chronic myeloid leukemia, Cytogenetics, Outcome, Prognosis
Session topic: CML: Molecular-cytogenetic diagnostics