CLINICIANS CORNER
Orthodontic treatment for a patient who
developed acute myeloid leukemia
Anne Marie Isaaca and Eleni Tholoulib
Dundee, Scotland, and Yorkshire, England, United Kingdom
Management of orthodontic treatment requires specific attention when patients develop medical
problems that affect their general health or require treatments that might not be compatible with
orthodontic care. This article describes the interface of orthodontic and medical care in a patient who
was diagnosed with acute myeloid leukemia midway through her orthodontic treatment. (Am J Orthod
Dentofacial Orthop 2008;134:684-8)
P
atients undergoing treatment with orthodontic
appliances can develop medical problems that
are unrelated to the orthodontic treatment but are
serious or even life-threatening. In this clinical report,
we highlight the interface of orthodontic and medical
management in a patient diagnosed with acute myeloid
leukemia (AML).
AML is the most common acute leukemia in adults.
It can occur in all age groups and includes 10% to15%
of childhood leukemias. The incidence in the United
Kingdom is approximately 2000 adults and 50 children
per year.1 Although most patients achieve complete
remission after chemotherapy, the relapse rate is high,
and the overall 5-year survival rate is only 40% to 50%
in those younger than 60 years.2 The most widely used
classification system for AML is the French-American-
British (FAB), which describes 8 variants (M0-M7).3
However, for treatment stratification, AML is primarily
subdivided into 3 main risk categories according to
cytogenetic abnormalities. This is used to guide treat-
ment with chemotherapy with or without bone marrow
transplantation.4
The clinical features of acute leukemias include
malaise, pallor, lethargy, fever, and infections of the
mouth, throat, skin, and perianal areas. Spontaneous
bruising, purpura, gingival bleeding, menorrhagia, and
bleeding from venipuncture sites are also common.
Tender bones and lymphadenopathy can occur, and
gingival hypertrophy is a frequent finding.
a
Clinical lecturer in orthodontics, Dundee Dental Hospital, University of
Dundee, Dundee, Scotland.
b
Registrar, University Department of Haematology, Manchester Royal Infir-
mary, Manchester, England.
Reprint requests to: Anne Marie Isaac, Jasmine Cottage, Well Bank, Well,
Bedale, North Yorkshire, DL8 2QG, England.
Submitted, July 2006; revised and accepted, October 2006.
0889-5406/$34.00
Copyright 2008 by the American Association of Orthodontists.
doi:10.1016/j.ajodo.2006.10.024
684
Some patients will initially have an oral problem.5
Due to the high incidence of gingival bleeding or hyper-
trophy, an orthodontic specialist, who sees the patient
routinely, might notice gingival changes and suspect
pathology. We report an orthodontic patient diagnosed
with AML midway through her orthodontic treat-
ment and encourage practitioners to be vigilant in
monitoring orthodontic patients, who are usually fit
and healthy. We also discuss the management chal-
lenges of these patients related to their immunocom-
promised state.
CASE REPORT
Our patient was 14 years 7 months old when she
came for orthodontic evaluation. She had a Class II
Division 2 incisor relationship on a Class II skeletal
base, with a reduced maxillary-mandibular plane angle
and normal lower face height. Her overjet was 2 mm
with an increased and complete overbite. The molar
relationship on both sides was Class I. Clinically, all
permanent teeth were present except the maxillary
lateral incisors. The maxillary permanent canines were
mesially positioned, adjacent to the central incisors. The
maxillary deciduous teeth were retained distally to the
permanent canines. There was mild mandibular labial
segment crowding, and oral hygiene was fair (Fig 1).
Radiographs confirmed a developing dentition with
agenesis of the maxillary lateral incisors and retained
maxillary deciduous canine teeth. The third molars
were developing.
Skeletally, she had a mild Class II pattern. SNA
angle was 77, SNB angle 74, SN/maxillary angle 8,
giving a corrected ANB angle of 5, by using the
Eastman correction. The maxillary/mandibular plane
angle was reduced at 21, and the maxillary incisors
were retroclined at 100 to the maxillary plane and the
mandibular incisors at 88 to the mandibular plane. The
American Journal of Orthodontics and Dentofacial Orthopedics
Volume 134, Number 5
Fig 1. Pretreatment intraoral photographs.
Fig 2. Initial alignment intraoral photographs.
lower face height was within normal limits at 56.3% of
total face height.
The treatment objectives were to improve oral
hygiene and dental esthetics.
Two treatment options were suggested to the patient
and her family. The first option was nonextraction
treatment in the mandible, with extraction of the decid-
uous teeth and space opening for prosthetic maxillary
lateral incisors. The second option was extraction of
the maxillary deciduous canines and the mandibular
permanent second premolars with space closure in
the maxilla. Reduction of the tips of the maxillary
canines would be necessary if the second option was
chosen.
The patient and her family took the second option,
and maxillary and mandibular fixed appliances were
placed after the extractions. The patient was then 14
years 10 months old. The initial archwires were
0.016-in nickel-titanium, and photographs taken after
initial alignment (Fig 2) show that her oral hygiene had
Isaac and Tholouli 685
improved, and there was no evidence of gingival
hyperplasia.
The patients family circumstances changed, and
we lost contact with her between the ages of 15 years 9
months and 16 years 6 months, despite repeated letters
from our department. However, she started to reattend
again after this period and was regular for the next 9
months. Her oral hygiene and gingival condition re-
mained good throughout this period. She progressed
through .018 .025-in nickel-titanium archwires to
.019 .025-in stainless steel archwires. It was there-
fore a surprise when she attended for a routine review
appointment at age 17 years 2 months with marked
gingival hyperplasia. Orthodontic space closure was
almost complete. Intraoral photographs were taken (Fig
3). The gingival hypertrophy in the area of the palatal
incisal papilla was particularly noticeable and unusual
for this patient. There were also other smaller areas of
gingival hypertrophy.
The patient had cancelled her scheduled appoint-
686 Isaac and Tholouli
Fig 3. Marked gingival hyperplasia.
ment 3 weeks earlier because she was feeling unwell.
She had been treated by her general medical practitio-
ner with amoxicillin for a suspected upper respiratory
tract infection. However, she continued to complain of
general malaise, sore throat, and cervical and axillary
lymphadenopathy. She was referred immediately by the
author to the oral pathology department of the dental
hospital for investigation. She did not wait for a blood
test that day, and an appointment was made for her to
return soon. During the next week, before any further
investigations were carried out, she developed severe
orbital cellulitis and was admitted to Manchester Royal
Infirmary, where the diagnosis of AML was made. She
began chemotherapy and returned to the orthodontic
department for review after her first cycle of leukemia
treatment.
At this appointment, the orthodontic consultant in
charge asked the patient whether the medical staff
supervising her treatment wanted the fixed appliances
to be removed. The patient and her family said that no
such instruction had been given, and the appliances
remained in place.
The patient underwent a second course of chemo-
therapy and was considered for an allogeneic bone
marrow transplant. A matched unrelated donor search
was started through the Anthony Nolan Trust in the
United Kingdom. A donor was identified, and, at age 17
years 9 months, she was admitted to the hospital on
very short notice for chemotherapy (fludarabine, cyclo-
phosphamide, and alemtuzumab), total body irradia-
tion, and bone marrow transplantation.
During the neutropenic period after transplantation,
she developed severe mucositis and facial cellulitis
while in isolation. This was despite oral hygiene mea-
sures and the use of mouth antiseptics. Her doctors
attributed this complication to severe mucosal inflam-
mation and secondary infection by bacteria retained on
the fixed orthodontic appliances. The mucositis and
facial cellulites were treated aggressively according to
protocols.
After hospitalization, she was eager to complete orth-
American Journal of Orthodontics and Dentofacial Orthopedics
November 2008
odontic treatment as soon as possible, and we decided to
debond. This was done within 6 weeks, because she was
close to completion of orthodontic space closure. The
treatment result was not perfect (Fig 4), but it satisfied this
young lady, who continued with immunosuppressive ther-
apy of cyclosporine A and prednisolone.
Unfortunately, our patient relapsed 6 months after
bone marrow transplantation for AML. Because of her
poor prognosis, she decided against further hemato-
logic treatment, and she died 2 months later, aged 18
years 5 months, at home.
DISCUSSION
This article reports the orthodontic treatment of a
patient diagnosed with AML midway through orth-
odontic therapy; it dramatically portrays the conse-
quences of retaining fixed orthodontic appliances dur-
ing neutropenic periods after chemotherapy, bone
marrow transplantation, and immunosuppressive ther-
apy.
An acquired hemorrhagic tendency is commonly
the first symptom of acute leukemia and should always
warrant further investigation. Gingival hyperplasia is
less common but is likely to be noticed by an attentive
orthodontist; this can lead to the diagnosis of AML.
Although any patient with AML can have some gingi-
val hyperplasia, some subtypes are more strongly asso-
ciated. Patients with FAB M4 or M5 often have severe
oral changes. This patient had the mixed-lineage-leu-
kemia gene rearrangement 11q23 found on cytogenetic
analysis. This is particularly associated with the FAB
M4 and M5 subtypes of AML.6
Severe pancytopenia occurs after intensive chemo-
therapy or radiotherapy of large body areas. It makes
the patient hemorrhagic and susceptible to pathogens.
After bone marrow transplantation, mucositis is a
common symptom of variable severity and occurs less
frequently after chemotherapy. This localized mucosal
inflammation is a port of entry for pathogens with the
potential for developing severe infections. Reversed
barrier nursing, oral hygiene measures, mouth antisep-
American Journal of Orthodontics and Dentofacial Orthopedics
Volume 134, Number 5
Fig 4. Intraoral photographs at debond.
tics, and prophylactic antibiotic and antifungal therapy
are used to generally minimize the risk of infections.
Despite these measures, this patient developed a life-
threatening infection of the facial tissues. The fixed
orthodontic appliances in-situ during treatment were
undoubtedly a risk factor for bacterial colonization of
the mouth and might have promoted the facial cellulitis.
The prevention and elimination of oral infections can
reduce morbidity and mortality of patients undergoing
bone marrow ablation.7,8 A suitable oral hygiene regi-
men for these patients has been outlined by Berkowitz
et al9 and Sheller and Williams.5
We suggest that all health care workers involved
with orthodontic patients diagnosed with hematologic
malignancies should liaise carefully and discuss remov-
ing the fixed orthodontic appliances. Some patients
might resist this suggestion if they are nearing the end
of orthodontic treatment, and all options, such as an
intermediate debond and temporary retainers, should be
discussed with them. Sheller and Williams5 suggested
that orthodontic treatment or its resumption should be
postponed for at least 2 years after bone marrow
transplantation. At this stage, immunosuppressive ther-
apy will usually have been stopped, and the risk of
hematologic relapse requiring further intervention is
reduced. In pediatric patients, the need for growth
hormone treatment could have been evaluated by this
time.
Our patient was admitted to the hospital for bone
marrow transplantation on short notice because of her
donors commitments. Such situations require careful
management by all team members. Patients are unlikely
Isaac and Tholouli 687
to initiate the removal of fixed orthodontic appliances
because of the psychological trauma caused by the
diagnosis of a potentially terminal illness. Our patient
was almost at the end of orthodontic space closure at
the time of her diagnosis, and it was possible to remove
her fixed appliances with a satisfactory orthodontic
outcome within 6 weeks of her return home after
transplantation.
CONCLUSIONS
Orthodontists are in a good position for detecting
intraoral signs of illness such as leukemia and must be
vigilant at all times. They might be able to diagnose a
hematologic malignancy at an early stage.
All health care workers involved in the care of
orthodontic patients with cancer, who are undergoing
chemotherapy or radiotherapy for marrow obliteration,
should understand the need to consult with the orth-
odontist to help prevent severe life-threatening infec-
tions.
It was a privilege to know and treat this patient. Her
family is grateful to the anonymous bone marrow
donor, who gave their daughter a few more months of
life, and wants to encourage orthodontists and staff to
consider becoming bone marrow donors and registering
with the Anthony Nolan Trust in the United Kingdom
or their local blood bank. We thank John A. L. Yin,
Stephen Chadwick, Catherine McDade, and Nicola
Mandall for their contributions.
688 Isaac and Tholouli
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