Contributions
Abstract: PB1873
Type: Publication Only
Background
The clinical course of chronic lymphocytic leukemia (CLL), the most common leukemia in western countries, is highly heterogeneous. Further stratification of CLL patients who may profit from novel targeted therapies is critically needed, particularly in high-risk patients.
Aims
To subdivide the high-risk CLL patients based on the clinical course, overall survival (OS) and treatment response.
Methods
Study cohort consisted of 116 high-risk CLL patients (F/M 36/80, median age 63 yrs, min-max 34-87 yrs) diagnosed between 2000 to 2015 in single reference centre. Besides genetic aberrations (del(11q), del(17p), TP53 mutation and complex karyotype, CK), age, gender, Binet stage, blood counts, beta-2-microglobulin, thymidinkinase, LDH, splenomegaly, bulky lymphadenopathy (>5 cm) at the time of diagnosis and clinical course, treatment response and OS were evaluated. Advanced data-mining methods were used to analyse the data.
Results
The network analysis revealed four subgroups of patients differing in their profiles of genetic aberrations, bulky lymphadenopathy, splenomegaly and gender. The best prognosis was observed for Profile (P)-I (n=47, predominantly men with del(11q) + no CK + no TP53 disruption) and P-II (n=29, men/women + del(11q) with CK + no TP53 disruption) with OS 70 and OS 54 mo, respectively. The ultra high-risk patients were those with P-III (n=19, predominantly women with del(17p)/TP53 mutation) and P-IV (n=21, men/women with CK + TP53 disruption) with OS 38 and OS 40 mo, respectively. The OS differed between (P-I and P-II) and (P-III and P-IV) (p<0.002). Of 54 patients treated with fludarabin, 33% were refractory (10.6% P-I, 13.8% P-II, 31.0% P-III, 14.3% P-IV). Adding rituximab to therapy did not improve OS in our patients regardless of profiles (p=0.98). Patients who required treatment shortly after diagnosis (<3 mo) had the shortest OS (48 mo) versus those treated later, evident in all profiles (OS 84 mo, p=0.037).
Conclusion
Our data showed that patients within P-III (women with del(17p)/TP53 mutation) and P-IV (men/women with CK and TP53 disruption) have the worst prognosis among high-risk patients. These ultra high-risk patients are candidates for novel upfront treatment algorithms.
Grant support: MZ ČR VES16-32339A
Session topic: 6. Chronic lymphocytic leukemia and related disorders - Clinical
Keyword(s): Chronic Lymphocytic Leukemia, High risk, Treatment
Abstract: PB1873
Type: Publication Only
Background
The clinical course of chronic lymphocytic leukemia (CLL), the most common leukemia in western countries, is highly heterogeneous. Further stratification of CLL patients who may profit from novel targeted therapies is critically needed, particularly in high-risk patients.
Aims
To subdivide the high-risk CLL patients based on the clinical course, overall survival (OS) and treatment response.
Methods
Study cohort consisted of 116 high-risk CLL patients (F/M 36/80, median age 63 yrs, min-max 34-87 yrs) diagnosed between 2000 to 2015 in single reference centre. Besides genetic aberrations (del(11q), del(17p), TP53 mutation and complex karyotype, CK), age, gender, Binet stage, blood counts, beta-2-microglobulin, thymidinkinase, LDH, splenomegaly, bulky lymphadenopathy (>5 cm) at the time of diagnosis and clinical course, treatment response and OS were evaluated. Advanced data-mining methods were used to analyse the data.
Results
The network analysis revealed four subgroups of patients differing in their profiles of genetic aberrations, bulky lymphadenopathy, splenomegaly and gender. The best prognosis was observed for Profile (P)-I (n=47, predominantly men with del(11q) + no CK + no TP53 disruption) and P-II (n=29, men/women + del(11q) with CK + no TP53 disruption) with OS 70 and OS 54 mo, respectively. The ultra high-risk patients were those with P-III (n=19, predominantly women with del(17p)/TP53 mutation) and P-IV (n=21, men/women with CK + TP53 disruption) with OS 38 and OS 40 mo, respectively. The OS differed between (P-I and P-II) and (P-III and P-IV) (p<0.002). Of 54 patients treated with fludarabin, 33% were refractory (10.6% P-I, 13.8% P-II, 31.0% P-III, 14.3% P-IV). Adding rituximab to therapy did not improve OS in our patients regardless of profiles (p=0.98). Patients who required treatment shortly after diagnosis (<3 mo) had the shortest OS (48 mo) versus those treated later, evident in all profiles (OS 84 mo, p=0.037).
Conclusion
Our data showed that patients within P-III (women with del(17p)/TP53 mutation) and P-IV (men/women with CK and TP53 disruption) have the worst prognosis among high-risk patients. These ultra high-risk patients are candidates for novel upfront treatment algorithms.
Grant support: MZ ČR VES16-32339A
Session topic: 6. Chronic lymphocytic leukemia and related disorders - Clinical
Keyword(s): Chronic Lymphocytic Leukemia, High risk, Treatment