Background: Accelerated-chronic lymphocytic leukemia (A-CLL) is a rare disease entity as it represents less than 1% of all reported cases of chronic lymphoid leukemia (CLL). Moreover, it is most likely an under diagno...Background: Accelerated-chronic lymphocytic leukemia (A-CLL) is a rare disease entity as it represents less than 1% of all reported cases of chronic lymphoid leukemia (CLL). Moreover, it is most likely an under diagnosed entity due to its rarity and the non-standardized practice of lymph node biopsy in CLL. Purpose: The aims of our work are to establish the diagnosis of A-CLL and to study the prognosis and treatment of this rare entity. Method: here, we report the clinical presentation and the follow up of two cases of A-CLL. Results: Distinguishing Richter transformation (RT) from A-CLL is important as it may result in a major change in disease management. The prognosis of A-CLL is intermediate between CLL and RT. The prognosis is mainly poor due to a predominance of poor prognostic markers including an increasing number of p53-positive cases. Conclusion: To this date, no prospective study has been led to define the best treatment for A-CLL. The shorter survival of A-CLL when compared to typical CLL implies the need of a more aggressive treatment.展开更多
Chronic lymphocytic leukemia(CLL)is common amongst leukemic malignancies,prompting dedicated investigation throughout the years.Over the last decade,the treatment for CLL has significantly advanced with agents targeti...Chronic lymphocytic leukemia(CLL)is common amongst leukemic malignancies,prompting dedicated investigation throughout the years.Over the last decade,the treatment for CLL has significantly advanced with agents targeting B-cell lymphoma 2(BCL2),Bruton's tyrosine kinase,and CD20.Single agents or combinations of these targets have proven efficacy.Unfortunately,resistance to one or multiple of the new treatment targets develops.Our review investigates various mechanisms of resistance to BCL2 inhibitors,including mutations in BCL2,alterations in the Bcl protein pathway,epigenetic modifications,genetic heterogeneity,Richter transformation,and alterations in oxidative phosphorylation.Additionally,the review will discuss potential avenues to overcome this resistance with novel agents such as bispecific antibodies,Bruton's tyrosine kinase(BTK)degraders,non-covalent BTK inhibitors,and chimeric antigen receptor T(CART).展开更多
文摘Background: Accelerated-chronic lymphocytic leukemia (A-CLL) is a rare disease entity as it represents less than 1% of all reported cases of chronic lymphoid leukemia (CLL). Moreover, it is most likely an under diagnosed entity due to its rarity and the non-standardized practice of lymph node biopsy in CLL. Purpose: The aims of our work are to establish the diagnosis of A-CLL and to study the prognosis and treatment of this rare entity. Method: here, we report the clinical presentation and the follow up of two cases of A-CLL. Results: Distinguishing Richter transformation (RT) from A-CLL is important as it may result in a major change in disease management. The prognosis of A-CLL is intermediate between CLL and RT. The prognosis is mainly poor due to a predominance of poor prognostic markers including an increasing number of p53-positive cases. Conclusion: To this date, no prospective study has been led to define the best treatment for A-CLL. The shorter survival of A-CLL when compared to typical CLL implies the need of a more aggressive treatment.
文摘Chronic lymphocytic leukemia(CLL)is common amongst leukemic malignancies,prompting dedicated investigation throughout the years.Over the last decade,the treatment for CLL has significantly advanced with agents targeting B-cell lymphoma 2(BCL2),Bruton's tyrosine kinase,and CD20.Single agents or combinations of these targets have proven efficacy.Unfortunately,resistance to one or multiple of the new treatment targets develops.Our review investigates various mechanisms of resistance to BCL2 inhibitors,including mutations in BCL2,alterations in the Bcl protein pathway,epigenetic modifications,genetic heterogeneity,Richter transformation,and alterations in oxidative phosphorylation.Additionally,the review will discuss potential avenues to overcome this resistance with novel agents such as bispecific antibodies,Bruton's tyrosine kinase(BTK)degraders,non-covalent BTK inhibitors,and chimeric antigen receptor T(CART).
