Treatment of chronic lymphocytic leukemia (CLL) is one of the most evolving fields of oncologic hematology. In the past few years several novel drugs, in particular B-cell receptor (BCR) and BCL-2 inhibitors, have been investigated in relapsed/refractory (R/R) and high-risk (HR) CLL patients, demonstrating impressive outcomes. These new agents may compete the use of allogeneic hematopoietic stem cell transplantation (HSCT), which at present is considered the only potentially curative treatment option in this setting of patients; nevertheless, transplant-related toxicity remains a relevant issue. For these reasons, the development of effective, well-tolerated agents, able to overcome the classical pathways involved in CLL refractoriness such as TP53 mutation or 17p chromosome (del(17p)), represents a challenge for consolidated treatment algorithms, requiring a critical review on the basis of new evidences. In this paper first we summarize clinical data regarding BCR and BCL-2 inhibitors and HSCT in CLL, then we discuss how these new drugs may change the actual therapeutic paradigm of R/R and HR-CLL.
