Numerical impairment of nestin+ bone marrow niches in acute GvHD after allogeneic hematopoietic stem cell transplantation for AML

Abstract

The nestin+ perivascular bone marrow (BM) stem cell niche (N+ SCN) may be involved in GvHD. To investigate whether acute GvHD (aGvHD) reduces the number of N+SCN, we examined patients with AML who had undergone allogeneic hematopoietic stem cell transplantation. In the test cohort (n=8), the number of N+SCN per mm2 in BM biopsies was significantly reduced in aGvHD patients at the time of aGvHD compared with patients who did not have aGvHD (1.2±0.78 versus 2.6±0.93, P=0.04). In the validation cohort (n=40), the number of N+SCN was reduced (1.9±0.99 versus 2.6±0.90 N+SCN/mm2, P=0.05) in aGvHD patients. Receiver operating curves suggested that the cutoff score that best discriminated between patients with and without aGvHD was 2.29 N+SCN/mm2. Applying this cutoff score, 9/11 patients with clinically relevant aGvHD (≥grade 2) and 13/20 with any type of GvHD had decreased N+SCN numbers compared with only 10/29 patients without clinically relevant aGvHD (P=0.007) and 6/20 patients without any type of GvHD (P=0.028). In patients tracked over time, N+SCN density returned to normal after aGvHD resolved or remained stable in patients who did not have aGvHD. Our results show a decrease in the number of N+SCN in aGvHD.