Comparing efficacy of reduced-toxicity allogeneic hematopoietic cell transplantation with conventional chemo-(immuno) therapy in patients with relapsed or refractory CLL: a Markov decision analysis

Abstract

Despite therapeutic advances, relapsed/refractory CLL, particularly after fludarabine-based regimens, remains a major challenge for which optimal therapy is undefined. No randomized comparative data exist to suggest the superiority of reduced-toxicity allogeneic hematopoietic cell transplantation (RT-allo-HCT) over conventional chemo-(immuno) therapy (CCIT). By using estimates from a systematic review and by meta-analysis of available published evidence, we constructed a Markov decision model to examine these competing modalities. Cohort analysis demonstrated superior outcome for RT-allo-HCT, with a 10-month overall life expectancy (and 6-month quality-adjusted life expectancy (QALE)) advantage over CCIT. Although the model was sensitive to changes in base-case assumptions and transition probabilities, RT-allo-HCT provided superior overall life expectancy through a range of values supported by the meta-analysis. QALE was superior for RT-allo-HCT compared with CCIT. This conclusion was sensitive to change in the anticipated state utility associated with the post-allogeneic HCT state; however, RT-allo-HCT remained the optimal strategy for values supported by existing literature. This analysis provides a quantitative comparison of outcomes between RT-allo-HCT and CCIT for relapsed/refractory CLL in the absence of randomized comparative trials. Confirmation of these findings requires a prospective randomized trial, which compares the most effective RT-allo-HCT and CCIT regimens for relapsed/refractory CLL.

Clinical Practice Recommendations for Use of Allogeneic Hematopoietic Cell Transplantation in Chronic Lymphocytic Leukemia on Behalf of the Guidelines Committee of the American Society for Blood and Marrow Transplantation

“…Three nonrandomized studies comparing allo-HCT versus nontransplant strategies provide evidence favoring the option of allo-HCT for relapsed or refractory CLL [31-33]. A Markov decision analysis published by Kharfan-Dabaja et al [31] demonstrated a better overall life expectancy favoring allo-HCT (35 versus 25 months).…”

High-dose therapy and autologous hematopoietic cell transplantation as front-line consolidation in chronic lymphocytic leukemia: a systematic review

“…[5][6][7][8][9][10][11][12] Allogeneic hematopoietic cell transplantation is the only known treatment modality that can offer the possibility of cure in CLL in approximately 50% of cases. [13][14][15] However, the procedure has been traditionally associated with increased morbidity and mortality preceding the evolution of reduced intensity conditioning regimens.…”

Monoclonal Antibodies in Conditioning Regimens for Hematopoietic Cell Transplantation

“…Accordingly, allo-HCT using reducedintensity conditioning (RIC) is now offered to patients of advanced age or with associated comorbidities who would not have been otherwise eligible for this procedure previously [31,32]. The development of RIC regimens occurred around the time when targeted therapies were being introduced into practice; thus, combining these approaches in an attempt to improve outcomes was a logical approach to pursue.…”