NorthWest Biotherapeutics Inc (NWBO)

[longusa]

Pyrr, if you look at the ref's NW posted in the PR about the trial mods,

The new variable involves the level of certain white blood cells in GBM patients when they finish the 6 weeks of daily radiation to the brain which is part of the current standard of care treatment. Important recent research has found that as many as 40% of GBM patients have such severely depressed white blood cell counts following radiation that their level is comparable to the level at which AIDs patients are put on continuous antibiotic treatments, prophylactically. Further, this research has found that these GBM patients’ white blood cell counts do not recover with the passage of time. See, for example: Grossman et al., 2011: Clin Cancer Res 17(16):5473-80; Ellsworth et al. 2014: Oncoimmunology 3(1):e27357. Epub 2014 Jan 3.

you find this one:
http://clincancerres.aacrjournals.org/content/17/16/5473.full.pdf

It' all about CD4:

Abstract
Purpose: Patients with high-grade gliomas (HGG) routinely receive radiation, temozolomide, and
glucocorticoids. As each of these is immunosuppressive, we conducted a prospective, multicenter study to
follow CD4 counts over time and determine whether low CD4 counts were associated with adverse
outcomes.

Experimental Design: Patients with newly diagnosed HGG had CD4 counts drawn before initiating
standard therapy and monthly thereafter for 1 year. Information on hospitalizations, infections, glucocorticoid
use, survival, and cause of death were also collected.

Results: Ninety-six evaluable patients were accrued [85% glioblastoma, median age of 57, median
Karnofsky performance status (KPS) ¼ 90]. The median CD4 count before radiation and temozolomide
treatment was 664 cells/mm3. The CD4 count nadir occurred 2 months after initiating therapy when 73%
of patients had CD4 counts less than 300 cells/mm3 and 40% had less than 200 cells/mm3. CD4 counts
remained low throughout the year of follow-up. Patients with CD4 counts less than 200 cells/mm3at
2 months had shorter survival than those with higher counts (median: 13.1 vs. 19.7 months, P ¼ 0.002).
Median survival was related to CD4 toxicity grades (I ¼ 23.8 months, II ¼ 19.7 months, III–IV ¼ 13.1
months, P ¼ 0.009). The adjusted HR for death attributable to 2-month CD4 count below 200 was 1.66
(P¼0.03). Eighty-eight percent of deaths resulted from disease progression, whereas only 2.5% were due to
infection.

Conclusions: Severe reductions in CD4 counts in patients with newly diagnosed HGG treated with
radiation and temozolomide treatment are common, treatment-related, long-lasting, and associated with
early death from tumor progression. Clin Cancer Res; 17(16); 5473–80.
2011 AACR.