STEM CELL

ABSTRACT Dental management prior to

The authors investigated oral health
treatment in patients scheduled for
hematopoietic stem cell transplantation.
Fifteen patients were scheduled for
bone marrow transplantation: 12 had
leukemia, two had aplastic anemia, and
one had myelodysplastic syndrome.
Twenty-three patients were scheduled to
undergo peripheral blood stem cell
transplantation: 20 had malignant lym-
phoma and three had leukemia.
Patients with platelet counts of
I 50,000/mm3 who required tooth
extraction and those with platelet counts
of I 30,000 /mm3 who required scaling
received platelet transfusions before the
dental treatment. We saw no bleeding
problems in these patients.
Dental care for patients who had
neutrophil counts of 2 500/mm3 included
tooth extractions or scaling, with no
postoperative infection. Even those with
severe immunosuppression (neutrophil
count: 100-150/mm3) tolerated treatment
when prophylactic measures, such as
intravenous administration of antibiotics,
were used. One patient with a neu-
trophil count of I 50/mm3 developed an
infection after even conservative thera-
py. Thus, caution should be exercised
when treating patients scheduled for
HSCT as even conservative therapy can
initiate and infection.
hematopoietic stem cell transplantation
Yoshinari Morimoto, DDS, PhD',''; Hitoshi Niwa, DDS, PhD'; Yuichiro Imai,
DDS, PhD2;Tadaaki Kirita, DDS, PhD2
'Department of Dental Anesthesiology, Graduate School of Dentistry, Osaka University, 1-8,Yamadaoka,
Suita, Osaka, 565-0871, Japan. 'Department of Oral and Maxillofacial Surgery, Nara Medical University,
Nara, Japan. 'Corresponding author E-mail: ysn-mori@dent.osaka-u.ac.jp
Spec Care Dentist 24(6): 287-292, 2004
Introduction
In patients undergoing hematopoietic stem cell transplantation (HSCT), severe infec-
tion is likely to occur due to pre-transplantation chemotherapy and post-transplanta-
tion immunosuppression; thus, it is necessary to eliminate sources of infection before
transplantation. The U.S. Center for Disease Control and Prevention (CDC) compiled
the Guidelinefor Preventing Opportunistic Infection Among Hematopoietic S t e m Ceft
Transplantation Recipients' in an attempt to provide effective evidence-based techniques
to eliminate infection sources.
The oral cavity contains numerous infection sources, and there have been many
reports on oral health management before and after bone marrow transplantation.2-6
These reports have emphasized the importance of maintaining oral health by brushing
or tooth extraction to eliminate lesions (apical lesions or periodontal disease) that can
serve as infection sources. However, in patients with severe hematological abnormali-
ties before HSCT, dental plans that differ from those designed for healthy individuals
are needed to prevent postoperative complications, such as infection, bleeding, and
poor wound healing.
Several have been published on the severity of hematological abnormali-
ties and oral health management, but there is no general consensus on this relationship
or regarding the onset of post-transplantation complications. In fact, surgical treatment
is often necessary before transplantation in patients with severe hematological abnor-
malities, and it is important to establish appropriate preoperative management tech-
niques. In our retrospective record review, we investigated preoperative management
techniques in patients undergoing HSCT in whom oral health management was carried
out before transplantation

Patients and methods ings (white blood cell count, neutrophil

All participants were patients undergoing
HSCT in whom pre-transplantation oral
health management was carried out in
our clinic over a five-year period
between 1997 and 2001. Medical charts
for these patients were reviewed to gath-
er information such as patient back-
ground factors (gender, age, disease),
number of days from initial dental visit
to transplantation, hematological find-
count, platelet count), dental treatment,
management, and complications.
Results
Of the HSCT recipients, 15 were sched-
uled to undergo bone marrow transplan-
tation (BMT) (nine men, six women;
average age, 35.941.3 years), and 23
were scheduled to undergo peripheral

Spec Care Dentist 24/61 2004 287

STEM CELL

blood stem cell transplantation (PBSCT)
(14 men, nine women; average age,
43.3515.1 years).
Of the 15 patients scheduled for
BMT, 12 had leukemia, two had aplastic
anemia and one had myelodysplastic
syndrome. Of the 23 patients scheduled
for PBSCT, 20 had malignant lymphoma
and three had leukemia. The average
number of days from initial dental visit
to transplantation was 33.8 days for
patients scheduled for BMT and 31.9
days for patients scheduled for PBSCT.
The results of peripheral blood tests for
the 20 patients who underwent PBSCT
because of malignant lymphoma showed
no severe abnormalities in white blood
cell count, neutrophil count, or platelet
count; thus, these patients were excluded
from tooth extraction and scaling analy-
ses.
Dental treatments
Among patients scheduled for BMT, the
following dental treatments were deliv-
ered:
three patients were treated for caries or
pulpitis;
four patients had root canal treatments;
six patients were treated with scaling
or curettage (including flap operation);
four patients had tooth brushing
instruction; and
four patients needed to have at least
one tooth extracted.
Three patients who had very low
neutrophil counts did not receive dental
treatment.
Among patients scheduled for
PBSCT, the following treatments were
completed:
four patients were treated for caries or
pulpitis;
three patients had root canal treat-
ments;
10 patients were treated with scaling
and curettage;
seven patients had tooth brushing
instruction; and
four patients had to have at least one
tooth extracted.
Two patients, who were scheduled to
undergo BMT and had severe immuno-
suppression with neutrophil counts of
less than 500/mm3, needed to have teeth
extracted. Because of the low neutrophil
counts. we administered antibiotic intra-
venously before extracting the teeth.
These patients did not develop any post-
operative infection. In addition, two
patients who also required dental extrac-
tions had platelet counts of 50,000/mm3
or less, but hemostasis was managed by
transfusing platelet concentrate (Table 1).
In one patient (Case No. 12),
myelodysplastic syndrome (that is,
refractory anemia with excess of blasts in
transformation; RAEB-t) caused pancy-
topenia, red cell concentrate and platelet
concentrate were transfused twice week-
ly. Although the patient’s neutrophil
count was very low at 135/mm3,extrac-
tions were planned while the patient was
in hospital because swelling and pain
recurred with both mandibular third
molars during chemotherapy. On the day
before extraction, the patient received
transfusions of two units of red cell con-
centrate and 10 units of platelet concen-
trate. In addition, before surgery, the
patient was given 2 g/day of flomoxef
sodium and 400 mg/day of isepamicin
sulfate intravenously Three impacted
third molars were extracted, and a flap
operation was done around tooth no. 32.
Antibiotics were administered intra-

Case No. Sex Age

Hemato-
logical
Surgical
Site
I Cell Counts
Prophylactic Procedures Conducted
Before Extraction

Disorder Crooth No.) White blood Platelet Antibiotic

Neutrophil
cell (cells x Administra- Transfusion Other
(ce11s/mm3)
(ce11s/mm3) 104/mm3) tion

Acute
6 Male 56 lymphocytic 23 5900 3540 7.9 None
leukemia

Myelodys- Red cell Granulocyte

18, 38,a
concentrate colony
12 Female 24 plastic 48,a 32 (flap 2900 135 3.5 Intravenous
Platelet stimulating
syndrome operation) concentrate factor

Acute Red cell

concentrate
14 Male 44 myelocytic 46,a48a 2700 721 3.8 Oral None
Platelet
leukemia
I I I I I I I
1 1 1 1
concentrate
Chronic
15 Male 51 myelocytic 14, 3 5 , 4 7 8000 480 14.2 Oral None None
leukemia

a Impacted tooth.

288 S p e c C a r e Dentist 24(6) 2 0 0 4 Dental management for HSCT


venously for five days after surgery, and
300 mg/day of cefdinir was given orally.
On the day after surgery, the white blood
cell count was 8900/mm3, the neutrophil
count was 1,335/mm3, and c-reactive
protein was 3.3 mg/dl, which were high,
but wound healing occurred without
postoperative infection (Figure 1).
A neutrophil count of 500/mm3or
above was recorded in all the patients
with leukemia who required scaling for
control of calculus except one. Post-scal-
ing infection was not seen in any of these
patients. The one patient mentioned
above had a neutrophil count of
180/mm3; thus, 250 pg/day of granulo-
cyte colony stimulating factor was given
subcutaneously, but no increase in neu-
trophil count was seen. Scaling was done
under antibiotic cover, which was intra-
venously administered. The patient did
not develop any infection following the
scaling procedure (Table 2).
Dental treatment was suspended for
three patients who were scheduled to
undergo bone marrow transplant. Two of
these patients had severe immunosup-
pression (neutrophil counts of about
ZOO/mm’). Because the neutrophil count
Morirnoto e t a / .
was so low, scaling was not done but oral
hygiene instruction was provided (Table
3). In a third patient (Case No. 13) who
had aplastic anemia, which caused severe
pancytopenia, red cell concentrate and
platelet concentrate were transfused
twice weekly. In addition, 250 pg/day of
granulocyte colony stimulating factor
was administered subcutaneously.
However, their white blood cell and neu-
trophil counts stayed very low at 600 and
0-6/mm3, respectively. At the initial den-
tal examination, the examiner noted gen-
eralized severe marginal periodontitis,
and swollen gingiva in this patient. Pus
was not observed probably due to the
very low neutrophil count. Because of
the immunosuppression, tooth brushing
instruction only was provided. The first
night after the dental examination, the
patient developed a fever of 39°C despite
taking 300 mg/day of levofloxacin orally.
In addition, the c-reactive protein count
increased to 19.9 mg/dl. The patient was
diagnosed with systemic inflammatory
response syndrome, and was adminis-
tered intravenously 2 g/day of imipen-
edcilastatin sodium, which gradually
alleviated the infection. Dental treatment
STEM CELL
was therefore suspended. While in a spe-
cially sterilized “clean room” after the
bone marrow transplantation, this
patient fasted and was managed by intra-
venous hyperalimentation. To minimize
any infection stemming from the patient’s
oral conditions, he gargled with povi-
done iodine and amphotericin B, and
received antibiotics intravenously.
Through these measures, the patient
recovered without developing any further
infection.
Discussion
This retrospective record review showed
that if platelet transfusion was performed
in patients with platelet counts of
50,000/mm3or less who needed tooth
extraction, or if they had platelet counts
of 30,000/mm3 or less, then scaling could
be done and no bleeding problems were
seen. Further, when immunosuppression
was severe (neutrophil count: 100-
150/mm3), it was possible to extract teeth
and scale them, if the patients were pro-
phylactically treated with intravenous
administration of antibiotics. If the pro-
tocol was followed, no postoperative
Spec Care Dentist 2 4 ( 6 ) 2004 289
STEM CELL
infections were seen. However, post-
treatment infection was encountered in
one patient who received restorative
treatment but he had a very low neu-
trophil count ( 50/mm3).
I reduced hemostasis due to low platelet
The CDC‘s Guidelinefor Preventing
Opportunistic Infection Among
Hernatopoietic Stern Cell Transplantation
Recipients’ recommends maintaining oral
health; removing lesions that can easily
lead to dental infections; extracting teeth
affected by moderate or severe periodon-
tal disease; and removing dentures and
orthodontic appliances.’ However, there
is no mention of which management
techniques should be used to safely carry
out dental procedures in these patients.
a This patient was scheduled to receive a peripheral blood stem cell transplant. All others were scheduled for bone marrow transplants.
Delivering dental treatment to
patients with hematological abnormali-
ties before transplantation can be prob-
lematic because these patients may have
count and immunosuppression due to
low neutrophil count. Platelet concen-
trate transfusions have been recommend-
ed9when treating patients with HIV who
had platelet counts of 50,000/mm3or less
to manage hemostasis. Our approach was
similar, and we were able to manage
bleeding without any problems.
Raut et al.’ reported that the inci-
dence of complications associated with
tooth extraction before transplantation
was low (13%) among 69 patients who
were scheduled to undergo HSCT and
chemotherapy, and who had neutrophil
counts of 1,400/mm3or above and
platelet counts of 34,000/mm3or above.
The authors concluded that this low inci-
dence of complications was attributed to
appropriate surgical technique and post-
operative management including antibi-
otic administration. However, Tai et
found that the incidence of postoperative
complications was 40% among 15
patients for whom symptomatic impact-
ed third molars were extracted, but this
high rate of complications may have
been due to existing infections the
patients had before undergoing the
extractions or that fact that the level of
J
 STEM CELL

surgical invasion was relatively high.

The use of antibiotics is recommend-
ed when carrying out dental treatment
for patients with HIV who have severe Cell Counts
Hemato-
immunosuppression (< 500-1000/mm3 Case Prescribed
Sex Age logical
neutrophils) .’We have adopted this stan- No.
Disorder (cells x 104,
dard for patients undergoing transplanta- mm3)
tion, and as a general rule, antibiotics are
administered orally or intravenously to 3 Male 16 Aplastic
anemia 1200 216 2.2 Brushing
patients who have neutrophil counts of
l,000/mm3 or less. In the present study, Acute
the neutrophil count of three patients 5 Male 43 rnyelocytic 1700 170 10.3 Brushing
leukemia
who underwent scaling and tooth extrac-
tion was 500/mm3 or less, but postopera- 13
Aplastic
600 6 0.4 Oral rinse
tive infection was not seen when we used Male 32 anemia
intravenous second-generation
cephalosporins. One patient who had a increased to 1,335/mm3the day after sur- ing antibiotics and carefully monitoring
very low neutrophil count of 135/mm3 gery, the wounds healed well and no the patient’s condition after surgery. In
(Case No. 12), received the second-gen- postoperative infection developed. particular, dental treatment should be
eration cephalosporin, which was com- Therefore, even when patients have done before transplantation, especially
bined with an aminoglycoside antibiotic, low neutrophil counts (100-150/mm3), it when there is an oral infection present.
and this combination therapy completely is possible to safely carry out invasive Among those patients for whom den-
suppressed any postoperative infection. dental procedures, such as scaling or tal treatment was suspended (Cases No.
Because the patient’s neutrophil count extraction, by intravenously administer- 3 and No. 5 ) because their neutrophil

Morimoto et a / S p e c C a r e D e n t i s t 24(6) 2004 291

S T E M CELL
count was very low (about ZOO/mm3),
their calculus deposition was mild and
their risk of oral infection was consid-
ered to be low, even without removal of
calculus. These patients were instructed
to maintain their oral health by brushing.
Because the neutrophil count was so low
(0-6/mm3)for one patient (Case No. 13),
brushing instruction was provided with a
new quinolone. Unfortunately, the
patient still developed a fever and subse-
quently developed systemic inflammato-
ry response syndrome due to a bacterial
infection from the gingival bleeding.
Because dental treatment is difficult to
perform before transplantation when the
patient has severe immunosuppression,
no dental treatment was carried out. This
patient was placed in a specially steril-
ized “clean room” after the bone marrow
transplant, the patient fasted, drank only
water, and was fed by intravenous hyper-
alimentation. The patient also gargled
with povidone iodine and amphotericin
B, and a third-generation cephalosporin
was also administered. Ultimately, the
patient recovered without developing an
oral infection. As the treatment of this
patient illustrates, caution should be
exercised when planning dental treat-
ment for a person who is severely
immunosuppressed (neutrophil count of
50/mm3or less) because a systemic
292 Spec Care Dentist 24(6) 2004
inflammatory response syndrome can
develop, even with conservative treat-
ment such as tooth brushing.
The average number of days from the
initial dental visit to transplantation was
33.8 days for patients scheduled for bone
marrow transplants and 31.9 days for
patients scheduled to undergo peripheral
blood stem cell transplantation. These
numbers represent the minimal length of
time for treating canes and infected root
canals before transplantation. In many of
these patients, it appears that they were
referred for a dental examination after he
or she had recovered from bone marrow
suppression caused by chemotherapy. As
a general rule, when oral surgery is need-
ed for these patients, we allow about a
two-week healing period before trans-
plantation. As a result, we have not had a
patient whose transplant procedure had
to be delayed due to poor wound healing.
References
1 Center for Disease Control and Prevention
Guidelines for preventlng opportunlstic mfec-
tion among hematopoietic stem cell trans-
plantation recipients MMWR 49 1-128,2000
2 Cutler LS Evaluation and management of the
dental patient with cancer-1 Complications
associated with chemotherapy OT hone mar-
row transplantation J Conn State Dent Assoc
61: 236-8, 1987.
3. Raber-DurlacherJE, Abraham-lnpijn 1,van
Leeuwen EF, Lustig KH, van Winkelhoff AJ.
The prevention of oral complications in
bone-marrow transplantations by means of
oral hygiene and dental intervention. NethJ
Med 34:98-108, 1989.
4. Maxymiw WG, Wood RE. The role of den-
tistry in patients undergoing bone marrow
transplantation. Br Dent J 167:229-34, 1989.
5. Heimdahl A, Mattsson T, Dahllof G, Lonnquist
B, Ringden B. The oral cavity as a port of
entry for early infections in patients treated
with bone marrow transplantation. Oral Surg
Oral Med Oral Pathol68:711-6, 1989.
6. Lazarchik DA, Filler SJ, Winkler MF! Dental
evaluation in bone marrow transplantation.
Gen Dent 43:369-71, 1995.
7. Raut A, Huryn JM, Hwang FR, Zlotolow 1M.
Sequelae and complications related to dental
extractions in patients with hematologic
malignancies and the impact on medical
outcome. Oral Surg Oral Med Oral Pafhol
92:49-55, 2001.
8. Tai CC, Precious DS, Wood RE. Prophylactic
extraction of third molars in cancer patients.
Oral Surg Oral Med Oral Pathol 78:151-5,
1994.
9. American Academy of Oral Medicine:
Clinician’s guide to treatment of HIV-infect-
ed patients. 3rd ed. Seattle, WA. [USA]:
AAOM. 2001.
Dental Management for HSCT