156 Impact of Bone Marrow Neuropathy On the Outcome of Autologous Stem Cell Transplantation (ASCT) for Lymphoma

Track: Contributed Abstracts
Wednesday, February 13, 2013, 6:45 PM-7:45 PM
Hall 1 (Salt Palace Convention Center)
Basem M. William, MD, MRCP , University Hospitals Case Medical Center, Cleveland, OH
Nermin Kady , Michigan State University, East Lansing, MI
Anamarija M. Perry, MD , University of Manitoba, Winnipeg, Canada
Kimberly Klinetobe , University of Nebraska Medical Center, Omaha, NE
Robert Gregory Bociek, MD , University of Nebraska Medical Center, Omaha, NE
Philip J. Bierman, MD , University of Nebraska Medical Center, Omaha, NE
Julie M Vose, MD , University of Nebraska Medical Center, Omaha, NE
James O Armitage, MD , University of Nebraska Medical Center, Omaha, NE
Dennis Weisenburger, MD , City of Hope National Medical Center, Duarte, CA
Julia V. Busik, PhD , Michigan State University, East Lansing, MI
Bone marrow is a highly innervated tissue with nerve fibers terminating in association with stromal cells.  Bone marrow neuropathy has been associated with abnormal hematopoietic stem cell (HSC) trafficking and activity in animal models of diabetes. There is also evidence that granulocyte colony-stimulating factor (G-CSF) mediates its mobilizing effect on HSC through modulation of norepinephrine release from adrenergic neurons. Therefore, we hypothesized that pre-existing bone marrow neuropathy may impair G-CSF driven HSC mobilization and/or time to engrafment in the context of ASCT for lymphoma. We retrospectively identified 46 ASCT patients, all of whom were mobilized with G-CSF. Twenty four patients were identified as poor mobilizers (PM) based on the need for rescue pleriaxfor after mobilization failure, while 22 patients were identified as good mobilizers (GM) based on the ability to collect the target HSC dose within two days of apheresis. We compared the clinical and immunohistochemical characteristics between the two groups.  The adequacy of bone marrow innervation was determined by semiquantitative immunohistochemistical scoring of tyrosine hydroxylase positive (TH+) nerve terminals in pre-ASCT bone marrow core biopsies. The mean TH scores were 2.33 for PM vs. 1.32 for GM (p=0.2). There was a non significant trend towards a longer time to neutrophil/platelet engraftment when no TH+ nerve terminals were identified vs. any TH+ terminals identified (11/11.4 vs.10.8/10.7 days respectively). HSC from the group with no TH+ nerve terminals had less colony forming units (CFU) compared to the group that had any TH+ terminals identified (7.1 vs. 10.4 x 106 CFU/kg, p=0.58). Also, the group with no TH+ nerve terminals had lower peripheral blood CD34+ cell counts, before collection and after G-CSF priming, compared to the group with any TH+ terminals identified (18.3 vs. 28.7/mm3, p=0.66). As expected, the time to neutrophil/platelet engrafment was higher in the PM compared to the GM group (11.5/13.3 vs. 10.3/8.6, p=0.004/p<0.0001, respectively). Owing to the small sample size, we can’t draw definite conclusions about the impact of bone marrow neuropathy on HSC mobilization and ASCT outcomes but we observed a trend toward higher HSC mobilization, longer time to engraftment and decreased HSC CFU capacity in patients with evidence of bone marrow neuropathy. This is consistent with what other investigators have demonstrated in animal models. Failure of G-CSF mobilization was associated with longer time to neutrophil and platelet engraftment in patients with lymphoma undergoing ASCT.
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