ABSTRACT
Background: In the largest study of Baliakas et al. (2019) the presence of at least 5 abnormalities, was associated with dismal clinical outcome, independently of the somatic hypermutation status and TP53 status. The presence of 3 or 4 aberrations is defined as clinically relevant in the absence of TP53. Studies by Kittai (2021) and Al-Sawaf (2020) showed the impact of karyotypic complexity on survival in patients with chronic lymphocytic leukemia (CLL) treated with ibrutinib or venetoclax. The complex karyotype (CK) is a topic that is being intensively researched, both in the aspect of increasing karyotypic complexity stratification and clonal evolution. Optimal therapy for patients with CLL has not yet been developed. The combination therapy of ibrutinib and venetoclax was superior to chlorambucil and obinutuzumab in terms of undetectable minimal residual disease (MRD) responses according to data from the GLOW trial (Tunir, 2021). The importance of achieving a complete response with undetectable MRD as the goal of therapy in CLL was proposed (Montserrat, 2005). Aims: The aim of our study is to evaluate the effectiveness of therapy with ibrutinib and venetoclax in combination for the patients with CLL and CK. Methods: This ambilinear observational study included patients with CLL with high genetic complexity (high-CK), defined as >=5 aberrations or CK (>=3 aberrations) in combination with a 17p deletion (CK+del17p). The first retrospective cohort included patients treated with ibrutinib monotherapy (Imono) to progression or intolerable toxicity since May 2015. The second prospective cohort included patients receiving ibrutinib in combination with venetoclax (IVen) since July 2019. Venetoclax therapy was started at the 3rd month of ibrutinib (from the escalation phase). Combination therapy was continued until a complete response, defined as three consecutive PET-CT-negative and MRD-negative results 3 months apart. If this criterion was not achieved at 24th month of therapy, venetoclax was discontinued and ibrutinib continued indefinitely. Results: Seventy-nine patients are included in the study. Twenty-nine patients in the first cohort and 50 patients in the second cohort. The characteristic is presented in Table. At the current follow-up periods, there were no significant differences in PFS and OS regarding a follow-up period <= 24 months (with the exception of death from COVID-19, since patients were not observed at parallel time intervals). In the group of patients treated with Imono, the majority of patients achieved partial remission or partial remission with lymphocytosis by 12 months. In 21 patients from Iven group, with a median follow-up of 7.4 months, a complete remission was achieved (72.4%);of these, 8 had unmeasurable MRD. Four patients did not complete the escalation period. There was a significant difference in the median MRD response achieved between 3 (log10>10) and 12 (log10<0,1) months in IVen group (p=0,03). In 2 patient from the IVen group progression of the disease was noted. Summary/Conclusion: Combination therapy with ibrutinib and venetoclax is an effective oral regimen for high-risk patients with complex karyotype disorders. PFS in both groups is currently not significantly different, which is obviously due to the short follow-up period. Patients receiving the IVen regimen achieve a significantly better response, which paves the way for allogeneic transplantation in these patients.
ABSTRACT
Healthy life expectancy (HALE) measures the quality of life a person expects to live. This study aims to find out the most associated factors of HALE at birth globally. The data of 212 countries came from the World Health Organization, Worldometer, World Bank, and United Nations. HALE at birth is considered as the dependent variable;and social, economic, and health factors are considered as the predictors. Descriptive statistics, Pearson’s correlation analysis, and multiple linear regression models were used as the statistical tools to reach the objective. The results revealed that HALE is found lower in Central African Republic and higher in Singapore. The highest death rate due to coronavirus disease 2019 (COVID 19), alcohol consumption rate, human immunodeficiency virus (HIV) prevalence rate, and average household size are found in Nicaragua, Moldova Republic, Eswatini, and Senegal, respectively. And the lowest recovery rate from COVID 19, and universal health coverage (UHC) service index are found in Tajikistan, and Montserrat, respectively. The recovery rate from COVID 19, UHC service index, gross domestic product (GDP), current health expenditure, tuberculosis (TB) incidence, tobacco smoking, HIV prevalence rate and average household size were significantly correlated with the HALE at birth. The multiple linear regression models identified that the UHC service index, alcohol consumption rate, HIV prevalence rate and average household size are the most associate factors of HALE at birth globally. Therefore, the necessary steps should be taken to maximize the UHC service index, and to minimize the alcohol consumption rate, HIV prevalence rate and average household size for increasing the HALE at birth in the world.