A non-invasive oral rinse assay predicts bone marrow engraftment and 6 months prognosis following allogeneic hematopoietic stem cell transplantation Carol Forster 1 , Guy Aboodi 1 , Jeff Lipton 2 , Michael Glogauer 1 1 Matrix Dynamics Group, Dental Research Institute, Faculty of Dentistry, University of Toronto, Toronto, ON, Canada; 2 Princess Margaret Hospital, Toronto, ON, Canada BACKGROUND: We have previously shown in a pediat- ric Hematopoietic stem cell transplant (HSCT) popula- tion that a non-invasive oral rinse can be used to monitor engraftment, neutrophil tissue delivery and susceptibility to infection post-HSCT. METHODS: Using the same oral rinse protocol, we studied neutrophil tissue delivery kinetics and its rela- tionship to clinical parameters and outcomes following HSCT in 29 adult patients. Oral neutrophil counts were compared to circulating neutrophil levels, oral mucositis scores and patient health status at 6 months post-HSCT. RESULTS: Neutrophils were detected on average 8.4 ± 3.4 SD days earlier in the oral tissues than in the blood circulation, enabling us to confirm successful engraftment more than one week earlier than when using blood neutrophil counts alone. As well, in this population the time-span between oral engraftment (OE) and blood engraftment (BE) was a consistent predictor of treat- ment outcome at 6 months following HSCT where a BE–OE of <6 days resulted in 100% of patients having a negative outcome. CONCLUSION: We conclude that monitoring the tim- ing of neutrophil delivery to the oral tissues with a non- invasive oral rinse has the potential to allow the physician to identify those patients who are at a high risk of HSCT failure within just a few weeks of the initiation of treat- ment. J Oral Pathol Med (2012) 41: 165–170 Keywords: hematopoietic stem cell transplantation; neutrophil; oral rinse Introduction Hematopoietic stem cell transplantation (HSCT) is a common therapy for patients with different hematopoi- etic disorders, both malignant and non-malignant (1, 2). Assessment of successful myeloid engraftment following HSCT has conventionally been defined as the first of three consecutive days the patient presents an absolute neutrophil count (ANC) of ‡0.5 · 10 9 ⁄ l post-HSCT. The ANC is the most common method for monitoring engraftment and susceptibility to infection (3, 4). How- ever, it was previously reported that some HSCT patients may present with an ANC that suggests engraftment, but continue to experience life threatening, prolonged or recurrent infection (5). This suggest that the ANC method can only provide information on whether engraftment of the donor bone marrow has occurred in the host but ultimately does not predict long-term success. The human mouth has a constant bacterial presence that is kept under control in part by a constant influx of neutrophils from surrounding periodontal tissues (6). Previous work in our laboratory has shown that the timing of neutrophil recovery in the oral cavity, follow- ing HSCT can be predictive of future infections post- engraftment in a pediatric population (7, 8). The oral rinse assay enables a non-invasive assessment of neu- trophil tissue delivery by measuring the level of neutrophils in oral tissues in patients recovering from HSCT. A murine HSCT model recapitulated these clinical findings and suggested that the kinetics of neutrophil delivery to tissues during the engraftment phase may indicate the Ôquality’ of both the bone marrow engraftment and the reconstitution of the immune system (8). The goal of the present study was to further investi- gate the proposed oral rinse assay by testing if this diagnostic rinse test has the potential to predict the success of HSCT treatment at 6 months post-HSCT in adult patients. We assessed the timing of oral engraft- ment along with clinical parameters including blood Correspondence: Dr. Michael Glogauer, DDS, PhD, Matrix Dynam- ics Group, Faculty of Dentistry, University of Toronto, Rm 221, Fitzgerald Bldg, 150 College St, M5S 3E2, Toronto, ON, Canada. Tel: +416 978 0168, Fax: +416 978 5956, E-mail: michael.glogauer@ utoronto.ca Accepted for publication August 4, 2011 doi: 10.1111/j.1600-0714.2011.01076.x J Oral Pathol Med (2012) 41: 165–170 ª 2011 John Wiley & Sons A/S Æ All rights reserved wileyonlinelibrary.com/journal/jop