Oral complications in patients treated with hematopoietic stem cell transplantation

The oral cavity is a common site of complications related to hematopoietic stem
cell transplantation (HSCT). Oral complications have a negative impact on
quality of life (QoL) and treatment outcomes. The knowledge on the incidence,
severity, burden of illness and consequences of oral complications in HSCT is
inadequate. This lack of clarity is reflected in a lack of effective oral
management regimens. The present observational international multicenter study
with the acronym *ORA-STEM* will be performed to attenuate the gap of knowledge
on the clinical characteristics, consequences and risk factors of oral
complications.
In addition, there is an urgent need to obtain a better insight in the role of
the oral environment (e.g., pre-transplant dental pathologies, oral microbiome,
salivary output and proteome) in the pathogenesis of oral complications.
Moreover, there is a paucity of studies directed to potential associations
between the oral and gastrointestinal (GI) microbiome, and their relative
contribution to oral and GI mucositis. Therefore, the participating Dutch
centers (AMC and RUMC) will perform a side study involving Dutch subjects only
aimed at further unravelling the impact of the local ecosystem on complications
in HSCT recipients.

We anticipate that the results will provide a scientific base for the
development of individualized preventive strategies.

Main study objectives:
* To Identify the incidence, severity and temporal relationships of subjective
and objective oral complications related to type of conditioning regimen in
HSCT recipients
* To determine which oral complications can predict negative clinical and
economical outcomes and reduced QoL
* To explore whether genetic polymorphisms in candidate genes demonstrate an
increased risk for the development of severe oral mucositis (OM) and graft
versus host disease (GVHD)

Additional study objectives of the Dutch side study:
* To determine whether a less diverse oral microbiome is associated with
increased incidence, severity, and duration of OM, and increased incidence and
severity of acute and chronic oral GVHD
* To assess whether decreased salivary output and an aberrant salivary proteome
are associated with increased incidence, severity, and duration of OM and
increased incidence and severity of acute and chronic GVHD
* To determine whether pre-existent periodontal disease increases the
incidence, severity and duration of OM and incidence and severity of acute and
chronic oral GVHD
* To assess whether chronic oral GVHD is associated with increased incidence
and activity of dental caries
* To explore potential associations between the oral and GI microbiome, and
whether having a less diverse GI microbiome is associated with the incidence,
severity, and duration of GI mucositis

Prospective observational multicenter study

The burden for patients is mild, as the study is observational, non-invasive
and involves questionnaires and oral examination with collecting of oral
rinsing and salivary samples before, during and after HSCT. Peripheral blood
samples and rectal swabs will be collected together with those obtained for
routine patient care as much as possible. There are no direct risks for
participating subjects in this study. Patients may benefit from frequent
structured oral assessments allowing early diagnosis of oral complications.