Study of the effects of cytotoxic chemotherapy on oral microcirculation in patients with acute myeloid leukemia (AML)

Mucosal tissues consist of cells that rapidly divide and renew the mucosal
lining of the oral and gastrointestinal tract. Studies have suggested that
microcirculatory alterations might precede epithelial damage seen in mucositis.
One of the principle components of the microcirculation in this respect seems
to be damage to the microvascular endothelium. The most debilitating and
painful side effect of radiation and chemotherapy is damage to this mucosa,
known as mucositis or stomatitis, which has significant impact on health,
quality of life, and economic outcomes for the cancer patient. Cytostatic
chemotherapeutic and/or antineoplastic drugs endanger patient health by
inviting infections (i.e. bacteraemia, fungaemia, and sepsis) and threaten the
efficacy of treatment regimes that limit the ability of patients in tolerating
antitumor treatment. Mucositis in its mild form presents an erythematous
atrophic lesion with intact mucosa exhibiting redness and nociception
equivalent to food-induced burns. Severe mucositis is characterized by
ulcerations that penetrate into the submucosa and cause a very painful
sensation which usually necessitates narcotic analgesics to manage the
patient*s discomfort. Even though the clinical symptoms of mucositis are
principally the result of epithelial damage, it is believed that changes in the
submucosal endothelium and connective tissue precede epithelial damage. Further
more cancer patients receiving any type of invasive medical intervention (i.e.
dental intervention, surgery, or accidental traumas) and/or acquisition of any
type of wounds, exhibit non- or bad wound healing of tissues.

The aim of this study is to elucidate the effects of chemotherapy on the oral
microcirculation of patients with acute myeloid leukemia (AML). Ara-C is a
stomatotoxic drug that is frequently used in treatment against AML and it can
destroy submucosal connective tissue which is closely located to
microcirculatory vascular beds. Here are some of the questions we aim to
address. What are the effects of cytotoxic chemotherapy on the microvasculature
of the oral mucosa in these cases? What is the behavior of the
microcirculation, its morphology, and its capillary density in the oral mucosa
following chemotherapeutic regimens? We want to test the hypothesis that
chemotherapy triggers microcirculatory derangements and this leads to (oral)
mucositis in cancer patients.

In this study we use the technique of sidestream dark-field (SDF) imaging to
determine the effects of cytotoxic chemotherapy on the microvasculature of the
buccal mucosa in patients receiving standard cytotoxic chemotherapy regimens.
Particular attention will be focused on the mean functional capillary density
(FCD) of the microcirculation in the oral mucosa of patients receiving
cytotoxic chemotherapeutic treatment for acute myeloid leukemia (AML). The
investigations that are conducted in this study are designed to assess the
microcirculation architecture and its functional status. The SDF imaging device
(MicroScan Video Microscope System, MicroScan BV, Amsterdam, The Netherlands)
is a mobile and noninvasive technique for studying tissue microcirculation.
Additional investigations coupled to this protocol include determination of
circulating levels of angiogenic factors such as vascular endothelial growth
factor (VEGF), basic fibroblast growth factor (bFGF) and matrix
metalloproteinases (MMPs).

1. Measurement time points for the chemotherapy group are:
Day 1 - T0 = before chemo
T1 = 10 minutes after start of first chemo
T2 = 30 minutes after chemo
T3 = 60 minutes after chemo
Days 2, 4, 6, 8

n.v.t.