Ex Vivo Expanded Cord Blood Natural Killer Cells Combined with Rituximab and High-Dose Chemotherapy and Autologous Stem Cell Transplantation for B Cell Non-Hodgkin Lymphoma.

Relapse is the major cause of failure of high-dose chemotherapy (HDC) with autologous stem cell transplantation (ASCT) for B cell non-Hodgkin lymphomas (B-NHL). Improvement strategies include use in combination with effective immunotherapies. We hypothesized that the combination of rituximab/HDC/ASCT with expanded cord blood (CB)-derived natural killer (NK) cells is safe and active in B-NHL. Patients with B-NHL age 15 to 70 years and appropriate ASCT candidates were eligible for the study. The CB units were selected without considering HLA match with the recipient. The CB NK cells were expanded from day -19 to day -5. Treatment included rituximab on days -13 and -7, BEAM (carmustine/etoposide/cytarabine/melphalan) on days -13 to -7, lenalidomide on days -7 to -2, CB NK infusion (108/kg) on day -5, and ASCT (day 0). The primary endpoint was 30-day treatment-related mortality (TRM); secondary endpoints included relapse-free survival (RFS), overall survival (OS), and persistence of CB NK cells. We enrolled 20 patients. CB NK cells were expanded a median of 1552-fold with >98% purity and >96% viability. We saw no adverse events attributable to the CB NK cells and 0% 30-day TRM. At median follow-up of 47 months, the RFS and OS rates were 53% and 74%, respectively. CB NK cells were detectable in blood for 2 weeks, independent of HLA-mismatch status. CD16 expression in donor NK cells was correlated favorably with outcome, and homozygosity for the high-affinity CD16 variant (158 V/V) in CB, but not recipient, NK cells was correlated with better outcomes. Our data indicate that the combination of expanded and highly purified CB-derived NK cells with HDC/ASCT for B-NHL is safe. CD16 expression in donor NK cells, particularly if homozygous for the high-affinity CD16 variant, was correlated with better outcomes.

The independently fractal nature of respiration and heart rate during exercise under normobaric and hyperbaric conditions.

To test the hypothesis that the fractal character of breathing and heart rate are independent, inter-breath intervals (IBI) and R-R intervals (RRI) were measured during rest and two levels of exercise at 1 and 2.8 ATA in a hyperbaric chamber in 18 male and female subjects (ages 19-74 years). Both RRI and IBI showed fractal properties. Fractal dimensions (D) for IBI were (mean +/- S.D.) 1.33 +/- 0.11, 1.29 +/- 0.12, 1.19 +/- 0.16 (rest, light and heavy exercise at 1ATA); 1.33 +/- 0.13, 1.25 +/- 0.13, 1.18 +/- 0.14 (same conditions at 2.8 ATA). Corresponding D for RRI were 1.19 +/- 0.11, 1.05 +/- 0.07 and 1.02 +/- 0.05 (1ATA); 1.20 +/- 0.10, 1.03 +/- 0.04 and 1.01 +/- 0.02 (2.8 ATA). The fractal dimension of each variable decreased with exercise and was unaffected by hyperbaric exposure. These two systems were not cross-correlated under any of the six conditions. During rest and light and moderate exercise at 1 and 2.8 ATA the results are consistent with heart rate variability and breathing rate variability being mutually independent of one another.

Adaptations in horizontal head stabilization in response to altered vision and gaze during natural walking.

The purpose of this study was to determine adaptations in head stability resulting from altered gaze control and vision during over-ground walking. Using over-ground walking permitted adaptations in walking velocity and cadence that are otherwise not possible during treadmill walking or walking-in-place. Gaze control and vision were manipulated by having 20 young adult subjects 1) walk naturally, 2) view a distant, earth-fixed target to enhance the vestibulo-ocular reflex (VOR), 3) view a head-fixed target to suppress the VOR, and 4) walk in darkness. Horizontal head and trunk angular velocities in space, walking velocity and cadence were measured. Root-mean-square head and trunk angular velocities were calculated and frequency analyses determined head-trunk movement patterns. Results demonstrated that when given the opportunity, subjects slowed down and decreased cadence in response to challenging tasks. Despite strongly reduced walking velocity and cadence, walking in darkness proved most challenging for head stabilization, indicating the importance of vision during this process. Viewing the earth-fixed target demonstrated the greatest head stability thereby, facilitating gaze stabilization. However, comparisons between the earth-fixed and head-fixed target conditions suggest a reciprocal relationship where gaze stability also facilitates head stability. This contribution of gaze stability to head stability is more important than vision alone as the head stabilization response was diminished during the VOR suppressed condition.