Allogeneic transplantation for high-risk chronic lymphocytic leukemia—a summary of a 16-year experience

Abstract

In the pathway inhibitor era, the number of allogeneic stem cell transplantation (ASCT) for chronic lymphocytic leukemia (CLL) continues to decrease and this approach should be offered only after careful risk-benefit assessment. Nevertheless, ASCT still remains only curative therapeutic modality for CLL, especially in countries with limited access to novel agents. Thirty patients with CLL at median age of 42 years at diagnosis (range 29–64) underwent ASCT between years 2002 and 2018. Thirteen patients were transplanted in complete remission (CR), ten patients achieved partial response (PR), and seven had stable disease. The median time from diagnosis to transplant was 4 years (range 0.5–12). Twenty-three patients received HLA-matched related donor stem cell grafts, and seven patients received either matched unrelated donor or HLA-mismatched grafts. Reduced intensity conditioning (RIC) and myeloablative regimen (MAC) were used in 24 and 6 patients, respectively. Mortality to day + 100 after transplant was 16% (8% for RIC only). Acute and chronic graft versus host disease (GVHD) developed in 40% and 63% of patients, respectively. Fifteen patients relapsed or progressed after transplant. Thirteen patients (43%) are alive at last follow-up and 10 (77%) remain in clinical CR. Median follow-up for survivors was 6.8 years (range 0.4–15.2). Three-year progression-free and overall survivals were 56% and 60%, respectively. These outcomes were better for patients who received RIC conditioning: 64% and 72%, respectively. CR at transplant was found to have favorable impact on post-allograft survival. RIC should be preferred over MAC. ASCT may remain a valuable option for some CLL patients.

Allogeneic hematopoietic cell transplantation after prior targeted therapy for high-risk chronic lymphocytic leukemia

“…1,2 However, with the widespread availability of targeted therapies such as ibrutinib, idelalisib, duvelisib, and venetoclax, the landscape of CLL treatment has changed markedly and the number of alloHCTs performed each year for CLL has substantially decreased. 3,4 Despite this trend, however, the outcome after alloHCT has been steadily improving in safety and efficacy over time in both standard-and high-risk patients. 5,6 Targeted therapies have proven efficacy but the prognosis of patients who receive targeted therapy after failure of chemoimmunotherapies (CITs) remains relatively poor if they have del(17p) and/or TP53 mutation.…”

Whether CAR-T cell bridging to allo-HSCT increases the incidence of graft-versus-host disease in patients with high-risk chronic lymphocytic leukemia

“…GVHD is the most common complication of allo-HSCT, particularly in high-risk CLL patients. Pretreatment schemes are associated with GVHD, and RIC regimen has a lower incidence of aGVHD than myeloablative conditioning [15]. In addition, incompatible HLA type, donor gender, and age are also risk factors for aGVHD [16].…”

Six-year follow-up and subgroup analyses of a phase 2 trial of venetoclax for del(17p) chronic lymphocytic leukemia

“… 1 , 2 , 3 , 4 Allogeneic stem cell transplantation has curative potential, but few patients are eligible; for those who are eligible, its use is limited by significant toxicities and a substantial risk of nonrelapse mortality. 5 , 6 , 7 More recently, noncytotoxic targeted therapies, such as inhibitors of BTK and BCL-2, have emerged as a preferred therapeutic approach for these patients at high risk. 1 , 2 …”