Long‐term outcome of immunologic autograft engineering

Abstract

Our phase III trial reported that autograft‐absolute lymphocyte count (A‐ALC) improved survival post‐autologous peripheral blood hematopoietic stem cell transplantation (APBHSCT) for a short‐term follow‐up of 2 years. We evaluated retrospectively in our phase III trial patients that the A‐ALC still confers survival benefit with a longer follow‐up. With a median follow‐up of 127.6 months, patients infused with an A‐ALC ≥ 0.5 × 109 cells/kg experienced better overall survival (HR = 0.392, 95% confidence of interval [CI]: 0.224–0.687, p < 0.001) and progression‐free survival (HR = 0.413, 95% CI: 0.253–0.677), p < 0.0004). This study supports that A‐ALC provides long‐term survival benefit post APBHSCT.

Impact of plerixafor use in the mobilization of blood grafts for autologous hematopoietic cell transplantation

“…Giving a higher number of lymphocytes after high‐dose chemotherapy might improve survival. In fact, a randomized study suggests that higher infused lymphocyte counts after high‐dose therapy are associated with better long‐term outcome in NHL patients 63,64 . In several retrospective analyses of NHL patients, early immune recovery (absolute lymphocyte count on d + 15 > 0.5 × 10 9 /L) after AHCT has been associated with better outcome especially in NHL patients 65 …”

“…In fact, a randomized study suggests that higher infused lymphocyte counts after high-dose therapy are associated with better longterm outcome in NHL patients. 63,64 In several retrospective analyses of NHL patients, early immune recovery (absolute lymphocyte count on d + 15 > 0.5 Â 10 9 /L) after AHCT has been associated with better outcome especially in NHL patients. 65 In general, hematologic recovery post-AHCT has been comparable with patients mobilized without PLER, but we have observed somewhat slower platelet recovery in patients receiving preemptive PLER for poor mobilization at least in NHL patients.…”

The Impact of Infused Autograft Absolute Numbers of Immune Effector Cells on Survival Post-Autologous Stem Cell Transplantation

“…A follow-up at median 10.6 years was conducted with all of the patients who were recruited and completed the phase III trial: the 13-years OS rate was 54% for the A-ALC ≥ 0.5 × 10 9 cells/kg group and 28% for the A-ALC < 0.5 × 10 9 cells/kg group ( p < 0.0007). The 13-years PFS rate following A-ALC ≥ 0.5 × 10 9 cells/kg was 46% versus 17% for those with an A-ALC < 0.5 × 10 9 cells/kg [ 22 ]. However, patients still relapsed despite being infused with an A-ALC ≥ 0.5 × 10 9 cells/kg.…”

Natural Killer Cells Are Key Host Immune Effector Cells Affecting Survival in Autologous Peripheral Blood Hematopoietic Stem Cell Transplantation

“…However, looking at the Kaplan–Meier survival curves, the differences in survival between the group that had lower autograft NK cells compared with the group that had higher number of autograft NK cells showed that the 5-year OS rates were approximately 80% for the patients who received autograft NK cells < 0.5 × 10 6 cells/kg, versus 70% for the patients infused with autograft NK cells ≥ 0.5 × 10 6 cells/kg ( p = 0.092), and the median follow-up for both groups has not been reached. The 5-year PFS rates were approximately 75% for the patients received autograft NK cells < 0.5 × 10 6 cells/kg versus 55% for the patients infused with autograft NK cells ≥ 0.5 × 10 6 cells/kg ( p = 0.048), and the median follow-up for both groups have not been reached [ 37 ]. In contrast, the same group reported superior overall survival in non-high risk cytogenetics multiple myeloma patients that received autograft NK cells ≥ 2.5 × 10 6 cells/kg (the 5-year OS rates approximately 95%) compared with patients that received autograft NK cells < 2.5 × 10 6 cells/kg (the 5-year OS rates approximately 65%) ( p < 0.006) [ 38 ].…”

“…CXCL12/CXC4 is a chemokine signal for NK cell trafficking. Multiple studies have shown that the combination of Plerixafor plus G-CSF mobilized more NK cells compared with just G-CSF for mobilization [ 37 , 65 , 66 , 67 , 68 ].…”