Novel Therapies and Their Integration into Allogeneic Stem Cell Transplant for Chronic Lymphocytic Leukemia

Abstract

Over the past decade, numerous advances have been made in elucidating the biology of and improving treatment for chronic lymphocytic leukemia (CLL). These studies have led to identification of select CLL patient groups that generally have short survival dating from time of treatment or initial disease relapse who benefit from more aggressive therapeutic interventions. Allogeneic transplantation represents the only potentially curative option for CLL, but fully ablative regimens applied in the past have been associated with significant morbidity and mortality. Reduced-intensity preparative regimens has made application of allogeneic transplant to CLL patients much more feasible and increased the number of patients proceeding to this modality. Arising from this has been establishment of guidelines where allogeneic stem cell transplantation should be considered in CLL. Introduction of new targeted therapies with less morbidity, which can produce durable remissions has the potential to redefine where transplantation is initiated in CLL. This review briefly summarizes the field of allogeneic stem cell transplant in CLL and the interface of new therapeutics with this modality.

Ceritinib Enhances the Efficacy of Substrate Chemotherapeutic Agent in Human ABCB1-Overexpressing Leukemia Cells In Vitro, In Vivo and Ex-Vivo

“…Conventional chemotherapy, using cytotoxic drugs to inhibit the proliferation of malignant cells or destroy malignant cells, has become the most common and primary clinical strategy in the treatment of blood malignancies. The targeted chemotherapeutic drugs, such as the first FDA-approved tyrosine kinase inhibitor (TKI) imatinib has been used for treating chronic myeloid leukemia (CML) patients with oncoprotein BCR-ABL expression, which has resulted in well-pleasing and remarkable treatment outcomes for the majority of CML patients [1-3]. Unfortunately, multidrug resistance (MDR) is still the main reason for the failure and relapse of leukemia chemotherapy using conventional or targeted chemotherapeutic drugs.…”

CLL: ibrutinib and transplantation ride together

“…7,8 In this issue of Bone Marrow Transplantation, Link et al 9 provide further evidence of the beneficial role of ibrutinib in this context. In this study, five patients with extensively pre-treated high-risk CLL received ibrutinib for progressive CLL at a median of 28 months after alloHCT.…”

Transplant for CLL: still an option?

“…Unlike with other therapies, the presence of known poorrisk features, including the presence of unfavorable genetic abnormalities (17p-, TP53 mutation) or refractoriness to purine analogs, does not negatively impact those outcomes. 3 In 2007, the European Blood and Marrow Transplant group identified patients who relapsed within 12 months of exposure to purine analogs, within 24 months of treatment with purine analog-based combination therapy, or patients with p53 abnormalities as appropriate candidates for HSCT. 4 The widespread application of HSCT has been limited by its toxicity, particularly in a patient population where the median age is 72.…”

“…Clotting factor VIII (FVIII) and FIX concentrates were first derived from human plasma, and in the 1990s, they were manufactured using the recombinant technology. 3,4 During the last 2 decades, the availability of safe and effective replacement therapy has changed the natural history of the disease, thanks to rapid bleeding control and the widespread use of prophylaxis, which is the standard of care aimed at avoiding crippling joint damage.…”