Hematopoietic Cell Transplantation and Other Cellular Therapies for Chronic Lymphocytic Leukemia

Chronic lymphocytic leukemia (CLL) is the most prevalent adult leukemia in the West. There have been significant advances in deciphering the molecular biology of CLL over the past three decades that has translated into the development initially of chemoimmunotherapy and, more recently, novel targeted drugs that have changed the therapeutic landscape for the disease. Despite these major strides, CLL remains an incurable disease, and allogeneic hematopoietic cell transplantation (allo-HCT) remains the only potential curative treatment option, and still has a role in patients with high-risk disease characteristics. Reduced-intensity conditioning allogeneic HCT is the preferred modality for most patients requiring an HCT unless a suitable allogeneic donor is not available. Early referral to a transplant center should be considered for patients with high-risk CLL based on genetic and molecular characteristics (TP53 lesions) and disease exhibiting relapse on kinase inhibitor-based therapies or failing to demonstrate response to venetoclax. Newer cellular immunotherapies including chimeric antigen receptor T-cell therapy are being actively investigated in CLL. In this chapter, we provide a comprehensive review of the evolving role of HCT and other cellular therapies for CLL in the modern era.