Clin Oral Invest
DOI 10.1007/s00784-017-2127-x
ORIGINAL ARTICLE
Oral health status in adult patients with newly diagnosed acute
leukemia
Rilana Busjan 1 & Justin Hasenkamp 2 & Gerhard Schmalz 1 & Rainer Haak 1 &
Lorenz Trümper 2 & Dirk Ziebolz 1
Received: 6 January 2017 / Accepted: 15 May 2017
# Springer-Verlag Berlin Heidelberg 2017
Abstract
Background The aim of this cross-sectional study was to eval-
uate the oral health of adult patients with newly diagnosed
acute leukemia.
Methods Patients with initially diagnosed acute myeloid
(AML) or lymphocytic (ALL) leukemia and a matched
healthy control (HC) group were included. The oral investi-
gation comprised inspection of the oral mucosa; the decayed
(D), missing (M), and filled (F) teeth (DMF-T) index; and a
detailed periodontal status. Subgingival biofilm samples were
analyzed (polymerase chain reaction) for the presence of se-
lected potentially periodontal pathogenic bacteria. Statistical
analysis was performed using Fisher’s exact test, chi-squared
test, and Mann-Whitney U test (significance level α = 5%).
Results Thirty-nine patients with leukemia (AML 26, ALL
13) and 38 HCs were included. Oral mucosal findings were
present in 62% of L compared to 0% of HC patients, whereby
gingival hyperplasia was the most detected finding.
Furthermore, a higher caries prevalence in leukemia patients
was shown (D value 3.64 ± 3.98 vs. 0.72 ± 1.72, p < 0.01).
The periodontal parameters were poorer in leukemia patients.
No substantial differences in microbiological findings of se-
lected bacteria were detected within L group and between L
and HC patients.
Clinical relevance: Adult patients with initially diagnosed acute leukemia
have a high dental treatment need, and thus, a comprehensive and fast
dental treatment is necessary to avoid systemic complications.
* Dirk Ziebolz
dirk.ziebolz@medizin.uni-leipzig.de
1
Dept. of Cariology, Endodontology and Periodontology, University
of Leipzig, Liebigstr. 10-14, 04103 Leipzig, Germany
2
Clinic for Hematology and Medical Oncology, University of
Goettingen, Goettingen, Germany
Conclusion The high prevalence of oral diseases supports the
demand of an early and consequent dental treatment of leuke-
mia patients, especially considering subsequent therapy.
Keywords Leukemia . Acute myeloid leukemia . Acute
lymphocytic leukemia . Caries . Periodontitis . Periodontal
bacteria
Introduction
Leukemia (L) is a generic term for malignant diseases character-
ized by an uncontrolled proliferation of immature blood cells.
These cells originate from a hematopoietic stem cell mutation
and can lead to bone marrow failure and end up in death [1].
Depending on the affected cell type and the clinical course, L
can be classified into lymphocytic and myeloid, as well as acute
and chronic types. The four main types therefore are the acute
myeloid (AML), the acute lymphocytic (ALL), the chronic my-
eloid (CML), and the chronic lymphocytic leukemia (CLL)
[2–4]. Acute leukemia is a severe disease, taking a fatal course
when untreated. The subtypes AML and ALL are heterogeneous
diseases, leading to rapid inhibition of the physiologic hemato-
poiesis, resulting in pancytopenia (anemia, granulocytopenia,
and thrombocytopenia) and its characteristic symptoms such as
fatigue, pallor, weakness, susceptibility to infections, and in-
creased bleeding tendency [2, 5, 6]. Oral health is a significant
factor in this group of at-risk patients, and dentists play an impor-
tant role in the therapy of these patients [7, 8]. On the one hand,
oral manifestations of L such as hyperplastic gingiva, bleeding
and petechiae, mucosal pallor, and bacterial, viral, and fungal
infections are well known [7–14]. Furthermore, L was added as
one of several risk factors for gingivitis and periodontal lesions
and was integrated into the BClassification system for periodontal
diseases and conditions^ [15, 16]. However, studies examining

the periodontal health of patients with leukemia are rare [17–19],
and up until now, the data about the oral health situation of adult
patients with untreated acute L, especially for Europe, are insuf-
ficient. In some cases, oral manifestations are important initial
symptoms in the early detection of L. In approximately 25% of
the patients with AML, dentists are involved in the diagnosis.
Beside of this, poor oral health is associated with a higher risk
of systemic infections and complications in patients with L [20,
21]. Accordingly, a sufficient dental therapy before chemothera-
py or stem cell transplantation can reduce the septicemia rate and
its fatal consequences [19, 21–25]. Current papers primarily de-
scribe case studies or retrospective studies with focus on AML
[12–14, 26–31] and are not able to illustrate the oral health situ-
ation of L patients before therapy. Consequently, knowledge
about oral conditions of L patients is insufficient and the concrete
need for treatment of initially diagnosed patients appears unclear.
The aim of the current study therefore was to evaluate the oral
health situation of adult patients with newly diagnosed acute
leukemia (AML and ALL). It was hypothesized that L patients
show a poorer oral health status compared to HC.
Methods
Study design
This cross-sectional, prospective, controlled, observational
study examined the oral health of patients with newly diag-
nosed acute leukemia compared to a healthy control group.
The trial was approved by the Ethics Committee of the
University Medical Center in Goettingen, Germany (No. 30/
1/14). All patients gave written informed consent before any
study-specific procedure.
Patients
Power calculation The case number of the current study was
estimated based on the primary outcome clinical attachment loss
(CAL). Based on the literature, 1.5-mm CAL can be seen as a
clinically relevant difference (standard deviation 0.5–1.5 mm).
To reach a power of 80%, a case number of 17 patients for each
group was determined. To reach a possibly high power, the aim
was the recruitment of at least the twofold of this patient number.
Thirty-nine consecutive patients with newly diagnosed acute
leukemia (L group: ALL 13, AML 26) were enrolled between
January 2015 and April 2015. The participants were hospitalized
in the Clinic of Hematology and Oncology of the University
Medical Center Goettingen to receive induction chemotherapy.
Criteria for exclusion were underage patients (<18 years), a poor
general health condition that prohibited oral examination, preg-
nancy, and autoimmune diseases such as rheumatoid arthritis or
chronical bowel diseases. In addition, highly immunocompro-
mised patients (severe neutropenia or thrombocytopenia) were
Clin Oral Invest
excluded from the investigation. The healthy patients (HC: con-
trol group) were examined in the Department of Preventive
Dentistry, Periodontology and Cariology of the University
Medical Center Goettingen. These patients came to dental
check-up for the first time to the department. They were matched
to the L patients by age, gender, and smoking habits (smoker,
former smoker, and non-smoker).
General medical data acquisition
The patients were given a standardized questionnaire record-
ing the medical history, asking for general diseases, habits
(smoking habits, alcohol abuse, etc.), and the general oral
health. The following parameters were taken from the pa-
tients’ records: gender, age, type of leukemia, day of diagno-
sis, stage of leukemia and comorbidities. Additionally, all pa-
tients answered a standardized periodontitis questionnaire,
which covered subjective symptoms of periodontitis during
the last 12 months using yes-no questions.
Oral examination
Oral examinations were executed in the patients’ rooms under
standardized conditions using a headlight, a mirror, and a
probe. The investigation comprised inspection of the oral mu-
cosa, dental examination (decayed, missing, and filled teeth
(DMF-T) index), examination of gingival inflammation (pap-
illary bleeding index (PBI)), and a detailed periodontal status.
Oral mucosal findings Patients were asked whether oral ini-
tial symptoms were one of the initial symptoms leading to the
diagnosis L. The oral mucosal findings were assessed visually.
Oral manifestations on the following sites were recorded:
gums, lips, cheeks, palate, and floor of the mouth. A special
focus was given on hyperplasia, petechiae, signs of inflamma-
tion (bleeding and erythema), coating of the mucosa (white or
discolored coating), mucosal pallor, necrotic tissue, and clin-
ical signs of bacterial, viral, or mycotic infections.
Dental status (DMF-T) The DMF-T index comprised
decayed (D), missing (M), and filled or crowned (F) teeth
(T) and added them to a final sum (possible range 0–28).
Third molars were not included [32].
Gingival inflammation (PBI) Fordetectionofgingivalinflam-
mation, the PBI was recorded on oral sides in the first and third
quadrants and on buccal sides in the second and fourth quadrants
by carefully sweeping the sulcus with a periodontal probe
(PCP15, Hu-Friedy, Chicago, IL, USA). Bleeding was evaluated
after 20 s: 0: no bleeding, 1: bleeding point, 2: number of bleeding
points/bleeding line, 3: bleeding fills up the interdental space, and
4: profuse bleeding, blood covers the tooth [33].
Clin Oral Invest
Periodontal condition The periodontal condition was record-
ed on six measuring points per tooth, using a millimeter-scaled
periodontal probe (PCP15, Hu-Friedy, Chicago, IL, USA). It
included the periodontal probing depths (PPD), the occur-
rence of bleeding (bleeding on probing (BOP)), and the clin-
ical attachment loss (CAL). The stage of the periodontal dis-
ease was evaluated according to the definition of Page and
Eke: [34]: (1) no/mild periodontitis, (2) moderate periodonti-
tis, and (3) severe periodontitis.
Microbiologic analysis
Subgingival biofilm and sulcular fluid samples were taken from
the four deepest periodontal pockets using sterile paper tips on two
(maxilla and mandibular) to a maximum of four teeth (first to
fourth quadrants) after tooth cleaning with a cotton roll. The mi-
crobiological analysis of the periodontal pathogenic bacteria was
conducted by the clinical laboratory of the Department of
Preventive Dentistry, Periodontology and Cariology, University
Medical Center Goettingen, using polymerase chain reaction and
the commercial test kit micro-IDent®plus (Hain Lifescience,
Nehren, Germany).
The following bacteria were detected (detection threshold
>102): Aggregatibacter actinomycetemcomitans (Aa) and (de-
tection threshold >103): Porphyromonas gingivalis (Pg),
Tannerella forsythia (Tf), Treponema denticola (Td), Prevotella
intermedia (Pi), Parvimonas micra (Pm), Fusobacterium
nucleatum (Fn), Campylobacter rectus (Cr), Eubacterium
nodatum (En), Eikanella corrodens (Ec), and Capnocytophaga
species (Cs).
Statistical analysis
Statistical analysis was carried out using the statistical pro-
gram SPSS, Version 22.0 (SPSS Inc., USA). Clinical and lab-
oratory parameters were evaluated and compared as follows:
Categorical parameters were compared with Fisher’s exact test
or the chi-squared test. All metric parameters were labeled as
not normally distributed (Kolmogorov-Smirnov test: p < 0.05)
and were evaluated and compared with the Mann-Whitney U
test. The level of significance was 5%.
Results
Patients
Overall, 39 patients (19 male, 20 female) diagnosed with acute L
were included. Twenty-six (66.7%) were diagnosed with AML
and 13 (33.3%) with ALL. The examination took place within a
mean value of 2.18 days (±2.46) after the L was diagnosed. The
mean blood values in the L group were for CRP 40.28 ± 53.87 mg/
l, for thrombocytes 86.59 ± 95.83 × 103/μl, and for leucocytes
41.68 ± 133.20 × 103/μl. Table 1 gives an overview of the patient
characteristics of both groups, listing gender, age, smoking habits,
and general health parameters.
Periodontitis questionnaire
Almost half of the L patients (19, 48.7%) said that they no-
ticed gum bleeding during the last 12 months. Eight (20.5%)
suffered from a swollen, 12 (30.77%) from a painful, and 13
(33.3%) from a sensitive gingiva. Twelve (30.77%) stated
they had had a periodontal therapy before. None of the healthy
control reported any periodontitis-related symptoms in the
periodontitis questionnaire.
Oral findings
Oral mucosal findings A total of nine patients (23.1% of the L
patients; 34.6% of the AML patients) named oral symptoms as
one of the initial symptoms leading to the diagnosis L. All of them
were diagnosed with AML (Table 2). While in the control group,
neither oral symptoms were reported by the patients nor any oral
mucosal findings were detected, 62% (24/39) of the L patients
showed oral mucosal lesions during screening (Table 2). No clin-
ical sign for bacterial, viral, or mycotic infections or necrotic
tissue was observed. Most mucosal findings were localized at
the gingiva followed by palate and cheeks, whereby especially
hyperplasia was detected (Table 2).
Dental findings While there was no significant difference in
DMF-T values between the L and HC groups, significantly higher
D (3.64 ± 3.98 vs. 0.72 ± 1.72, p < 0.01) and M values (7.26 ± 7.56
vs. 3.38 ± 4.47, p = 0.02) were found in patients with L (Table 3).
No significant difference was found between AML and ALL.
Gingival inflammation (PBI) The L group had a mean PBI of
0.81 ± 0.82, which was significantly higher than the PBI of the
control group (0.30 ± 0.54, p = 0.005, Table 3). No significant
difference between the AML and ALL patients was found.
Periodontal findings Table 4 gives an overview of the peri-
odontal parameters. Periodontal screening could be carried out
on 34 of the 39 L patients (AML 23, ALL 11) and on all patients
of the control group; 82.4% of the L patients and 79.5% of the HC
had a moderate to severe periodontitis (p = 0.515). Thereby, within
the L group, AML showed significantly higher prevalence for
moderate (AML 56.5%, ALL 27.3%) and severe periodontitis
(AML 39.1%, ALL 27.3%, p = 0.012). For all periodontal param-
eters(BOP,PPD,CAL),significantlyhighervalueswerefoundfor
theL comparedtothe HC groupandwithintheL patientsforAML
compared to ALL (p < 0.05). In the L group, age tended to have an
influence on periodontitis severity (p = 0.051). In the HC group,
age also had a significant influence on the severity of the
 Clin Oral Invest

Table 1 Patients’ characteristics

AML ALL Leukemia Control p Test

[n = 26; 66.7%] [n = 13; 33.3%] [n = 39] [n = 38] value

Gender Male (%) [count] 46.2% [12] 53.8% [7] 48.7% [19] 50% [19] 1 Fisher test 2-sided
Female (%) [count] 53.8% [14] 46.2% [6] 51.3% [20] 50% [19]
Age in years 60.73 ± 14.67 44.5 ± 16.97 55.61 ± 17.01 55.63 ± 16.05 0.952 Mann-Whitney
(mean ± StDev) [63] [50.0] [57] [57.5] U test
[median]
Smoking Smoker 26.9% [7] 15.4% [2] 23.1% [9] 21.1% [8] 0.820 Chi-squared test
behavior Non-smoker 69.2% [18] 84.6% [11] 74.4% [29] 73.7% [28] 2-sided
(%) [count] Former smoker 3.8% [1] 0% [0] 2.6% [1] 5.3% [2]
General Overall general 73.1% [19] 53.8% [7] 66.7% [26] 10.5% [4] 0.297 Fisher test 2-sided
disorders disorders
(%) [count] Thereof 38.5% [10] 25.0% [3] 34.2% [13] 15.4% [6] 0.068 Fisher test 2-sided
hypertension
Thereof diabetes 11.5% [3] 8.3% [1] 10.5% [4] 0.0% [0] 0.055 Fisher test 2-sided
mellitus
Days since diagnose 1.69 ± 2.04 3.25 ± 3.02 [2.00] 2.18 ± 2.46 – 0.063 Mann-Whitney U
(mean ± StDev) [1.00] [1.00] test
[median]

periodontal disease (p = 0.038). For both groups, gender and
smoking habits had no significant influence (p > 0.05).
Microbiologic findings
Periodontal pathogenic bacteria could be detected in all patients
(Table 5). E. corrodens (Ec) was detected in significantly more
patients of the L group (76.9%) than in the HC patients (50%;
p = 0.018). T. denticola (Td) occurred significantly more often in
the HC group than in the L patients (HC 57.9%; L 30.8%;
p = 0.022). There was no significant difference between the preva-
lenceofperiodontalpathogensinAMLandALLpatients(p>0.05).
Discussion
Summary of the main results The L patients investigated in
the current study showed a high number of oral mucosal
findings, with more conspicuity for AML. Furthermore, a
poorer dental status (higher D-T and M-T) compared to the
HC group was detected. The periodontal parameters BOP,
PPD, and CAL were worse in L compared to HC, as well as
in AML compared to ALL. No substantial differences in the
microbiological findings of selected periodontal pathogenic
bacteria were detected within L and between L and HC.
Comparison with available literature To interpret the cur-
rent study’s results, the low number of available data must be
considered. While there are several studies about the oral sta-
tus of children with L [35–39], only few investigations pay
attention to adult patients [18, 20, 40]. An important point in
patients with L is the presence of oral mucosal findings. Of the
39 patients examined for this study, nine patients (23.1%)
reported oral initial symptoms. All of them were diagnosed
with AML (36.6% of all AML patients). This corresponds
with the literature and speaks for a realistic and representative

Table 2 Oral mucosal findings of patients within leukemia group

AML (n = 26) ALL (n = 13) Total (n = 39) Localization

Oral initial symptoms 9 0 9 –

Patients with at least one oral mucosal 18 6 24 –
lesion during screening
Type of mucosal findings Gingiva Tongue Cheeks Floor of mouth Palate Lips
Hyperplasia 12 1 13 13 0 2 0 8 1
Petechia 6 4 10 4 1 4 2 1 0
Signs of inflammation 7 1 8 3 0 2 0 2 3
Coating of the mucosa 6 2 8 0 5 1 0 0 0
Mucosal pallor 10 3 13 5 0 0 0 0 0

Signs of inflammation include erythema and bleeding of mucosa

Clin Oral Invest

Table 3 Caries parameters and PBI index

AML ALL p- Leukemia Control p Test

Wert (N = 39) (N = 38) value

DMF-T (mean ± StDev) 19.54 ± 5.06 17.00 ± 8.43 0.437 18.69 ± 6.38 16.62 ± 7.4 [17.00] 0.275 Mann-Whitney
[median] [19.00] [17.00] [19.00] U test
D-T (mean ± StDev) 3.62 ± 4.33 [2.00] 3.69 ± 3.33 [3.00] 0.577 3.64 ± 3.98 [3.00] 0.72 ± 1.72 [0.00] 0.000
[median]
M-T (mean ± StDev) 7.19 ± 7.24 [5.00] 7.38 ± 8.46 [4.00] 0.540 7.26 ± 7.56 [4.00] 3.38 ± 4.47 [2.00] 0.017
[median]
F-T (mean ± StDev) 8.73 ± 5.17 [9.00] 5.92 ± 4.97 [8.00] 0.135 7.79 ± 5.22 [8.00] 12.51 ± 5.95 0.000
[median] [13.00]
Papillary bleeding 0.88 ± 0.88 [1.00] 0.64 ± 0.67 [1.00] 0.499 0.81 ± 0.82 [1.00] 0.30 ± 0.54 [0.00] 0.005
index (PBI)
(mean ± StDev) [median]
valid N Leuk 36, Kontr 27

patient group [9, 14]. During the oral inspection, mucosal
changes were found in 69.23% of the AML and in 46.15%
of the ALL patients. Overall, 62% (24/39) of the L patients
showed oral mucosal lesions during screening, what corre-
sponds to the findings of Stafford et al. stating that two thirds
of patients with L show non-specific oral lesions [9]. Thereby,
gingival hyperplasia was the most prevalent clinical finding.
In available investigations, gingival hyperplasia in patients
with acute L has been repeatedly described, and was discussed
to be an early clinical sign of acute L [26–30].
This high prevalence of oral mucosal findings in the L patients
shows how important it is especially for dentists to be aware of the
correlation between oral and systemic diseases, as dentists can be
at a key position in the early diagnosis of acute leukemia [9, 14].
Considering the fact that a poor oral health status in leukemia
patients can lead to severe systemic complications in the course
of the disease, either due to the disease itself or to the treatment,
dental and periodontal diseases are of high interest [17, 22, 23].
As a major finding of the current study, a high prevalence of
dental caries (D value) in L patients was detected. L patients
had significantly more decayed teeth requiring treatment
(3.64 ± 3.98) than the HC patients (0.72 ± 1.72; p < 0.01).
Meanwhile, no difference between AML and ALL was found.
Similar high caries prevalence has been shown in literature; how-
ever, the available studies investigated leukemic children [38, 39,
41]. As data about caries for adult patients with acute L are miss-
ing, no valid hypothesis can be formed about the reason for the
high caries prevalence. Up until now, salivary changes during the
cancer therapy were discussed to influence caries in leukemic
children [38, 39, 41]. This presumption can neither be confirmed
nor be disproved by the current study, as newly diagnosed pa-
tients were investigated who did not receive any cancer therapy
yet. However and regardless, the high D-T in the L group rein-
forces the need for a dental examination before therapy, especial-
ly to ensure the vitality of teeth with deep cavities and to prevent
an inflammation in the progress of the disease and therapy.

Table 4 Periodontal parameters

AML ALL p Leukemia Control p Test

(n = 23) (n = 11) value (N = 34) (N = 38) value

Bleeding on probing (BOP) 30.26 ± 18.02 20.00 ± 23.78 0.025 26.94 ± 20.29 2.25 ± 0.96 0.001 Mann-Whitney
(mean ± StDev [median]) [28.00] [13.00] [20.00] [2.5] U test
Probing depth (mean ± StDev 2.84 ± 1.45 [3] 1.95 ± 0.94 [2] 0.000 2.58 ± 1.38 [2] 2.30 ± 1.18 0.000 Chi-squared
[median]) [2] test
Clinical attachment loss 3.16 ± 1.95 [3] 2.34 ± 1.76 [2] 0.000 2.91 ± 1.94 [2] 2.47 ± 1.28 0.000 Chi-squared
(mean ± StDev) [median] [2] test
Probing depth (%), [count] 0–3 mm 68.1% [332] 93.6% [205] 0.000 76% [537] 85.7% [806] 0.000 Chi-squared
N = number of teeth: >3–6 mm 29.4% [144] 6.4% [14] 22.3% [158] 14.0% [132] test
L: N = 707, HC: N = 940 >6 mm 2.5% [12] 0.0% [0] 1.7% [12] 0.2% [2]
Clinical attachment Loss CAL (%), 0–3 mm 63.9% [312] 88.6% [194] 0.000 71.6% [506] 81.3% [764] 0.000 Chi-squared
[count] N = number of teeth: >3–6 mm 28.5% [139] 6.8% [15] 21.8% [154] 18.2% [171] test
L: N = 707, HC: N = 940 >6 mm 7.6% [36] 4.6% [10] 6.6% [46] 0.5% [5]
Periodontal degree (Page and Mild/healthy 4.3% [1] 45.5% [5] 0.012 17.6% [6] 20.5% [8] 0.515 Chi-squared
Eke [34]) (%), [count] Moderate 56.5% [13] 27.3% [3] 47.1% [16] 56.4% [22] test
Severe 39.1% [9] 27.3% [3] 35.3% [12] 23.1% [9]
 Clin Oral Invest

Table 5 Prevalence of periodontopathogenic bacteria

Bacteria AML (N = 26) ALL (N = 13) Leukemia (N = 39 Control (N = 38) p Test

(% [count]) (% [count]) (% [count])) (% [count]) value

Aa 0 [0] 15.4 [2] 5.1 [2] 5.3 [2] 1.000 Fisher test 2-sided
Pg 30.8 [8] 33.3 [4] 30.8 [12] 42.1 [16] 0.349
Tf 50.0 [13] 61.5 [8] 53.8 [21] 73.7 [28] 0.098
Td 30.8 [8] 30.8 [4] 30.8 [12] 57.9 [22] 0.022
Pi 23.1 [6] 7.7 [1] 17.9 [7] 23.7 [9] 0.584
Pm 65.4 [17] 69.2 [9] 66.7 [26] 57.9 [22] 0.458
Fn 96.2 [25] 84.6 [11] 92.3 [35] 92.1 [34] 1.000
Cr 50.0 [13] 38.5 [5] 46.2 [18] 52.6 [20] 0.651
En 23.1 [6] 23.1 [3] 23.1 [9] 28.9 [11] 0.610
Ec 73.1 [19] 84.6 [11] 76.9 [30] 50 [19] 0.018
Cs 80.8 [21] 61.5 [8] 74.4 [29] 78.9 [30] 0.789

Detection threshold >102

Aa Aggregatibacter actinomycetemcomitans, Pg Porphyromonas gingivalis, Tf Tannerella forsythia, Td Treponema denticola, Pi Prevotella intermedia,
Pm Parvimonas micra, Fn Fusobacterium nucleatum, Cr Campylobacter rectus, En Eubacterium nodatum, Ec Eikanella corrodens, Cs
Capnocytophaga species

Additionally, a higher degree of gingival (PBI) and periodontal
(BOP) inflammation was detected in L patients compared to HC.
A comparable investigation by Angst et al. showed similar results
[18]. In that study, no correlation between platelet count and
gingival and periodontal bleeding was detected [18]. It can there-
fore be assumed that the higher PBI and BOP in the current study
reflect an increased periodontal inflammation in patients with L
compared to healthy individuals. Higher PPD and CAL values
were found in L patients, and in addition, higher values were
found for AML compared to ALL patients. This, in combination
with the higher number of oral mucosal findings, might indicate
increased oral manifestations of AML compared to ALL, which
is in accordance to literature [9, 18, 42]. Therefore, the gingival
manifestations (e.g., leukemic infiltrate) might lead to worse peri-
odontal conditions. These findings, however, are limited by the
small sample size of the ALL group and the large difference in
age between AML and ALL. Furthermore, the higher amount of
patients with a diabetes mellitus in L compared to HC limits the
comparability of the groups regarding periodontal status. Poor
gingival and periodontal health is associated with an increased
risk for systemic infections in leukemia patients [20]. Periodontal
inflammation is primarily caused by periodontal pathogenic bac-
teria and is especially characterized by a shift in subgingival
biofilm [43, 44]. Considering the fact that the oral cavity is an
important entry point for systemic infections [45], periodontal
pathogenic bacteria might play an important role in the cause of
systemic complications. The current study therefore analyzed the
prevalence of 11 selected periodontal pathogenic bacteria. No
clear differences were found between L and HC, which corre-
sponds well to the findings of Wahlin et al. [46]. However, the
periodontal inflammation leads to damage and increased perme-
ability of junctional epithelium, which simplifies bacteria to enter
the blood [47–49]. In this way, periodontal pathogenic bacteria
might lead to bacteremia and systemic infections in L patients.
Although the prevalence of these bacteria in patients with L is not
higher compared to HC, under the consideration of the increased
periodontal inflammation, a higher risk for bacteremia is con-
ceivable for L patients. Consequently, a reduction of periodontal
inflammation in L patients should be performed to reduce the risk
of systemic infections. Overall, the results of the current study
show an inadequate oral situation in patients with untreated acute
leukemia and therefore suggest the necessity of a comprehensive
dental therapy. Referring to a current position paper, a dental
therapy requires dentists with awareness of the disease and ther-
apy and should be performed in an integrated health care plan-
ning [23]. With a dental treatment, systemic infections might be
reduced by approximately one third, if it is performed compre-
hensively andconsequently [21,23].Thecurrentstudy’s findings
support the demand for an interdisciplinary dental special care of
patients with acute leukemia, as the burden of oral diseases ap-
pears high in this patient group.
Strengths and limitations This study gives a comprehensive
overview of the oral health situation of adult L patients right at the
beginning of the disease. The fact that patients were examined
shortly after diagnose makes sure that medication has not yet had
any influence on the oral health, which is especially important
when looking at the initial symptoms of the disease. However,
limitation is given by the small number of patients in the ALL
group, which might result in a too low power of the results for
comparison between ALL and AML. Accordingly, the ability to
provide a strong clinical correlation is strictly limited by the small
sample size. Consequently, the findings between ALL and AML
are only preliminary and need validation in larger groups.
Nevertheless,patientswithacuteLoftensufferfromapoorgeneral
health status, making patient recruitment difficult. Accordingly,
Clin Oral Invest
the considerable number of 39 patients in the L group is remark-
able. Another limitation is the age difference between ALL and
AML, as it is known that the severity of periodontitis increases
with the age [50, 51]. However, AML regularly affects patients
withahighermeanage[5].Afurtherpointistheunclearoralhealth
history of patients in the L group and of healthy control patients
who were for the first time for dental check-up in the Department
of Preventive Dentistry, Periodontology and Cariology of the
University Medical Center Goettingen. One conspicuous point
is the absence of any periodontitis-related symptoms in the assess-
ment of the periodontitis questionnaire within the control group.
Different studies showed a reasonable prevalence of self-reported
periodontal symptoms like bleeding or pain of the gums in a sys-
temically healthy group [52–54]. It is unclear why the HC partic-
ipants did not report any of these symptoms. The fact that they
came for dental check-up might point to a control-oriented, moti-
vated patient group. This could result in a well-performed oral
hygiene and absence of periodontal symptoms, what might be
supported by the low average PBI. However, this is only specula-
tive, but serves as a limitation of the current study.
Additionally, it is not possible to say in which extent the pres-
ence of L has an influence on oral health. Despite these limita-
tions, the study was able to gain insight into the actual treatment
need for patients with acute L and supported the need for an
interdisciplinary, comprehensive dental treatment. In this con-
text, not only changes in oral health findings during therapy,
but also influence of oral diseases on the outcome and systemic
complications during L therapy might be of interest for future
investigations.
Conclusion
The oral examination of the leukemia patients showed a high
number of oral mucosal findings, high caries prevalence, and
increased periodontal inflammation especially in patients with
AML, making a high need for dental treatment of this patient
group apparent. Consequently, the demand for an early com-
prehensive and consequent dental treatment of leukemia pa-
tients, especially considering the subsequent chemotherapy or
stem cell transplantation, is supported by the current study’s
results.
Acknowledgments The authors would like to thank M. Hoch of the
Dept. of Preventive Dentistry, Periodontology and Cariology, University
Medical Center Goettingen, Germany, for the support in the laboratory
microbiological analysis and Dr. T. Kottmann of the Clinical Research
Organisation, Hamm, Germany, for performing the statistical analysis.
Compliance with ethical standards
Conflict of interest Rilana Busjan declares that she has no conflict of
interest. Justin Hasenkamp declares that he has no conflict of interest.
Gerhard Schmalz declares that he has no conflict of interest. Rainer
Haak declares that he has no conflict of interest. Lorenz Trümper declares
that he has no conflict of interest. Dirk Ziebolz declares that he has no
conflict of interest.
Funding The work was not funded.
Ethical approval The study was approved by the Ethics Committee of
the University Medical Center in Goettingen, Germany (No. 30/1/14).
Informed consent Patients were informed verbally and in writing
about the study and gave written informed consent.
References
1. Howard MR, Hamilton PJ (2013) Haematology: an illustrated colour
text, 4th edn. Churchill Livingstone, Edinburgh, New York, pp 33–66
2. Cripe LD (1997) Adult acute leukemia. Curr Probl Cancer 21(1):1–64
3. Swerdlow SH. WHO classification of tumours of haematopoietic and
lymphoid tissues. 4th ed. Lyon: International Agency for research on
cancer; 2008. World health organization classification of tumours
4. Harris NL, Jaffe ES, Diebold J et al (2000) The World Health
Organization classification of neoplastic diseases of the
haematopoietic and lymphoid tissues: Report of the Clinical
Advisory Committee Meeting, Airlie House, Virginia, November
1997. Histopathology 36(1):69–86
5. Khaled S, Al Malki M, Marcucci G (2016) Acute myeloid leuke-
mia: biologic, prognostic, and therapeutic insights. Oncology
(Williston Park) 30(4):318–329
6. Stock W (2010) Adolescents and young adults with acute lympho-
blastic leukemia. Hematol Am Soc Hematol Educ Program 2010:
21–29. doi:10.1182/asheducation-2010.1.21
7. Zimmermann C, Meurer MI, Grando LJ, Gonzaga Del Moral JA,
da Silva Rath IB, Tavares SS (2015) Dental treatment in patients
with leukemia. J Oncol 2015:571739. doi:10.1155/2015/571739
8. Lowal KA, Alaizari NA, Tarakji B, Petro W, Hussain KA,
Altamimi MAA (2015) Dental considerations for leukemic pediat-
ric patients: an updated review for general dental practitioner. Mater
Sociomed 27(5):359–362. doi:10.5455/msm.2015.27.359-362
9. Stafford R, Sonis S, Lockhart P, Sonis A (1980) Oral pathoses as diag-
nostic indicators in leukemia. Oral Surg Oral Med Oral Pathol. 50(2):
134–139
10. Barrett AP (1986) Oral changes as initial diagnostic indicators in
acute leukemia. J Oral Med 41(4):234–238
11. Orbak R, Orbak Z (1997) Oral condition of patients with leukemia
and lymphoma. J Nihon Univ Sch Dent 39(2):67–70
12. Lim H-C, Kim C-S (2014) Oral signs of acute leukemia for early
detection. J Periodontal Implant Sci 44(6):293–299. doi:10.5051/
jpis.2014.44.6.293
13. Wu J, Fantasia JE, Kaplan R (2002) Oral manifestations of acute
myelomonocytic leukemia: a case report and review of the classifi-
cation of leukemias. J Periodontol 73(6):664–668. doi:10.1902/jop.
2002.73.6.664
14. Fatahzadeh M, Krakow AM (2008) Manifestation of acute mono-
cytic leukemia in the oral cavity: a case report. Spec Care Dentist.
28(5):190–194. doi:10.1111/j.1754-4505.2008.00039.x
15. Kinane DF (1999) Periodontitis modified by systemic factors. Ann
Periodontol 4(1):54–64. doi:10.1902/annals.1999.4.1.54
16. Armitage GC (2000) Development of a classification system for
periodontal diseases and conditions. Northwest Dent 79(6):31–35
17. Shankarapillai R, Nair MA, George R, Walsh LJ (2010) Periodontal
and gingival parameters in young adults with acute myeloid leukae-
mia in Kerala, South India. Oral Health Prev Dent 8(4):395–400

18. Angst PDM, Dutra DAM, Moreira CHC, Kantorski KZ (2012)
Periodontal status and its correlation with haematological parame-
ters in patients with leukaemia. J Clin Periodontol. doi:10.1111/j.
1600-051X.2012.01936.x
19. Bergmann OJ, Ellegaard B, Dahl M, Ellegaard J (1992) Gingival
status during chemical plaque control with or without prior mechan-
ical plaque removal in patients with acute myeloid leukaemia. J
Clin Periodontol 19(3):169–173
20. Allareddy V, Prakasam S, Allareddy V et al (2015) Poor oral health
linked with increased risk of infectious complications in adults with
leukemia. J Mass Dent Soc 64(3):38–42
21. Elad S, Thierer T, Bitan M, Shapira MY, Meyerowitz C (2008) A
decision analysis: the dental management of patients prior to hema-
tology cytotoxic therapy or hematopoietic stem cell transplantation.
Oral Oncol 44(1):37–42. doi:10.1016/j.oraloncology.2006.12.006
22. Morimoto Y, Niwa H, Imai Y, Kirita T (2004) Dental management
prior to hematopoietic stem cell transplantation. Spec Care Dentist
24(6):287–292
23. Elad S, Raber-Durlacher JE, Brennan MT et al (2015) Basic oral care
for hematology-oncology patients and hematopoietic stem cell trans-
plantation recipients: a position paper from the joint task force of the
Multinational Association of Supportive Care in Cancer/International
Society of Oral Oncology (MASCC/ISOO) and the European Society
for Blood and Marrow Transplantation (EBMT). Support Care Cancer
23(1):223–236. doi:10.1007/s00520-014-2378-x
24. Greenberg MS, Cohen SG, McKitrick JC, Cassileth PA (1982) The
oral flor as a source of septicemia in patients with acute leukemia.
Oral Surg Oral Med Oral Pathol 53(1):32–36
25. Bergmann OJ (1989) Oral infections and fever in immunocompro-
mised patients with haematologic malignancies. Eur J Clin
Microbiol Infect Dis 8(3):207–213
26. Demirer S, Ozdemir H, Sencan M, Marakoglu I (2007) Gingival
hyperplasia as an early diagnostic oral manifestation in acute mono-
cytic leukemia: a case report. Eur J Dent 1(2):111–114
27. Sonoi N, Soga Y, Maeda H et al (2012) Histological and immunohis-
tochemical features of gingival enlargement in a patient with AML.
Odontology 100(2):254–257. doi:10.1007/s10266-011-0051-0
28. Vourexakis Z. 2015 Oral lesions presenting as an early sign of acute
leukaemia. Case Reports. 2015(jan29 1):bcr2014205100-
bcr2014205100. doi:10.1136/bcr-2014-205100
29. Guan G, Firth N (2015) Oral manifestations as an early clinical sign
of acute myeloid leukaemia: a case report. Aust Dent J 60(1):123–
127. doi:10.1111/adj.12272
30. Hasan S, Khan NI, Reddy LB (2015) Leukemic gingival enlarge-
ment: report of a rare case with review of literature. Int J Appl Basic
Med Res 5(1):65–67. doi:10.4103/2229-516X.149251
31. Babu SP, Kashyap V, Sivaranjani P, Agila S (2014) An undiagnosed
case of acute myeloid leukemia. J Indian Soc Periodontol 18(1):95–
97. doi:10.4103/0972-124X.128257
32. WHO (1997). World Health Organization: oral health surveys, ba-
sic methods 4th Edition. WHO; Oral Health Unit, Genf
33. Lange DE, Plagmann HC, Eenboom A, Promesberger A (1977)
Clinical methods for the objective evaluation of oral hygiene.
Dtsch Zahnarztl Z 32(1):44–47
34. Page RC, Eke PI (2007) Case definitions for use in population-
based surveillance of periodontitis. J Periodontol 78(7 Suppl):
1387–1399. doi:10.1902/jop.2007.060264
35. Valéra M-C, Noirrit-Esclassan E, Pasquet M, Vaysse F 2014. Oral
complications and dental care in children with acute lymphoblastic
leukaemia. J. Oral Pathol. Med. doi:10.1111/jop.12266
Clin Oral Invest
36. Azher U, Shiggaon N (2013) Oral health status of children with
acute lymphoblastic leukemia undergoing chemotherapy. Indian J
Dent Res 24(4):523. doi:10.4103/0970-9290.118371
37. Mathur VP, Dhillon JK, Kalra G (2012) Oral health in children with
leukemia. Indian J Palliat Care 18(1):12–18. doi:10.4103/0973-
1075.97343
38. Javed F, Utreja A, Bello Correa FO et al (2012) Oral health status in
children with acute lymphoblastic leukemia. Crit Rev Oncol
Hematol 83(3):303–309. doi:10.1016/j.critrevonc.2011.11.003
39. Hegde AM, Joshi S, Rai K, Shetty S (2011) Evaluation of oral
hygiene status, salivary characteristics and dental caries experience
in acute lymphoblastic leukemic (ALL) children. J Clin Pediatr
Dent 35(3):319–323
40. Gazi M, Ashri N, Lambourne A (1991) Oral health care of Saudi
leukemic patients. Ann Saudi Med 11(2):184–188
41. Joshi S, Hegde AM, Rai K, Shetty S (2013) Evaluation of salivary sialic
acid levels in acute lymphoblastic leukemic children and its correlation
with dental caries experience. J Clin Pediatr Dent. 37(3):309–313
42. Hou GL, Huang JS, Tsai CC (1997) Analysis of oral manifestations
of leukemia: a retrospective study. Oral Dis 3(1):31–38
43. Socransky SS, Haffajee AD, Cugini MA, Smith C, Kent RL (1998)
Microbial complexes in subgingival plaque. J Clin Periodontol
25(2):134–144
44. Berezow AB, Darveau RP (2011) Microbial shift and periodontitis.
Periodontol 55(1):36–47. doi:10.1111/j.1600-0757.2010.00350.x
45. Wilson W, Taubert KA, Gewitz M et al (2007) Prevention of infec-
tive endocarditis: guidelines from the American Heart Association:
a guideline from the American Heart Association Rheumatic Fever,
Endocarditis, and Kawasaki Disease Committee, Council on
Cardiovascular Disease in the Young, and the Council on Clinical
Cardiology, Council on Cardiovascular Surgery and Anesthesia,
and the Quality of Care and Outcomes Research Interdisciplinary
Working Group. Circulation 116:1736–1754
46. Wahlin YB, Holm AK (1988) Changes in the oral microflora in patients
withacuteleukemiaandrelateddisordersduringtheperiodofinduction
therapy. Oral Surg. Oral Med. Oral Pathol. 65(4):411–417
47. Bosshardt DD, Lang NP (2005) The junctional epithelium: from
health to disease. J Dent Res 84(1):9–20
48. Tomas I, Diz P, Tobias A, Scully C, Donos N (2012) Periodontal
health status and bacteraemia from daily oral activities: systematic
review/meta-analysis. J Clin Periodontol 39(3):213–228. doi:10.
1111/j.1600-051X.2011.01784.x
49. Hirschfeld J, Kawai T (2015) Oral inflammation and bacteremia:
implications for chronic and acute systemic diseases involving ma-
jor organs. Cardiovasc Hematol Disord Drug Targets 15(1):70–84
50. Hoffmann TMS. Vierte deutsche Mundgesundheitsstudie(DMS IV).
Köln: Dt. Zahnärzte-Verl., DÄV. Materialienreihe / Institut der
Deutschen Zahnärzte; 31
51. Eke PI, Dye BA, Wei L, Thornton-Evans GO, Genco RJ (2012)
Prevalence of periodontitis in adults in the United States: 2009 and
2010. J Dent Res 91(10):914–920. doi:10.1177/0022034512457373
52. Abbood HM, Hinz J, Cherukara G, Macfarlane TV (2016) Validity
of self-reported periodontal disease: a systematic review and meta-
analysis. J Periodontol 87(12):1474–1483
53. Dietrich T, Stosch U, Dietrich D, Kaiser W, Bernimoulin JP,
Joshipura K (2007) Prediction of periodontal disease from multiple
self-reported items in a German practice-based sample. J
Periodontol 78(7 Suppl):1421–1428
54. Taylor GW, Borgnakke WS (2007) Self-reported periodontal dis-
ease: validation in an epidemiological survey. Jnnnnnnnnnnn 78(7
Suppl):1407–1420