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RESEARCH Open Access
The effects of Bleomycin A5 on infantile
maxillofacial haemangioma
Quan-feng Luo* and Fu-yun Zhao
Abstract
Objective: To examine the effects of bleomycin A5 on infantile maxillofacial haemangiomas.
Methods: Bleomycin A5 was given by multiple intralesinoal injections and the dosage was given according to the
age of the patient and size of the lesion. Parts of patients were accompanied by prednisone treatment(2-5 mg/kg,
po, QOD.
Results: All the haemangiomas involuted completely after treated with bloemycin A5 with better recovery of skin
color and less scar forming in small haemangiomas.
Conclusion: Infantile haemangioma could be effectively treated with bleomycin A5 without serious side effects.
Introduction
Infantile hemangiomas are the most common tumor of
infancy, which are benign vascular proliferations com-
posed of densely packed capillaries with endothelial cells
and pericytes expanding in a lobular pattern. In contrast
to vascular malformations, infantile hemangiomas are
usually absent or inconspicuous at birth and are charac-
terized by a remarkably rapid postnatal proliferation and
slow spontaneous involution. Although infantile hae-
mangiomas can involute spontaneously, it is still difficult
to predict the progression of some infantile haeman-
gioma, even small lesions may result in major aesthetic
handicap at certain sites, especially for the big infantile
haemangiomas (> 4 cm), as it may develope to the
extant of maxillofacial deformity and follow with com-
plications (usually bleeding, ulceration, or obstruction).
Therefore, some clinicians suggest that interfering in
infantile haemangioma should be at the early stage[1-3].
Conservative therapies for infantile haemangiomas
include pharmacotherapy, laser therapy and consulting
doctors regularly.
Bleomycin (BLM, also known as Blenoxane) was first
isolated as a Cu2+-containing glycooligopeptide antibio-
tic from the culture medium of streptomyces verticul-
lust. It was soon found to be an anticancer agent and
has ever since become one of the most widely used
anticancer drugs[4-6].
New application of bleomycin A5 was found recent
years, that it was also used in treating haemangioma
[1-3]. Conrad Pienaar and his colleagues treated heman-
gioma with a standard injection of bleomycin of 0.3 to
0.6 mg/kg per injection. 73% patients had a response
rate greater than 75% reduction in size of the heman-
gioma. None of the patients in their study received cor-
ticosteroids. Only was bleomycin A5 injected in the
local site, no other drugs were used. Other scholars
achieved similar results that bleomycin A5 was effective
in treating haemangioma.
We used bleomycin A5 as sclerosing agent for infan-
tile haemangiomas for more than 15 years, prednisone
treatment accompanied with bleomycin A5 according to
the patient’s age and the size of haemangioma. In the
present study, we reviewed the effects of bleomycin A5
on infantile haemangiomas treated during 1997-2005 in
Peking University Hospital of Stomatology.
Materials and methods
Patients
A total of 82 cases of infantile haemangioma treated
with bleomycin A5 during 1997-2005 in Peking Univer-
sity Hospital of Stomatology was reviewed. The patients
(male 34 cases and female 48 cases) were presented
within their first year of life with the majority before 4
* Correspondence: LQF6668@163.com
Peking University School and Hospital of Stomatology, Department of Oral
and Maxillofacial Surgery, #22 Zhongguancun Nandajie, Haidian District,
Beijing 100081, P.R. China
Luo and Zhao Head & Face Medicine 2011, 7:11
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HEAD & FACE MEDICINE
© 2011 Luo and Zhao; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative
Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly cited.
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months old (Figure 1). The size of the haemangioma is
mostly less than 6 cm (Figure 2).
Diagnosis of infantile haemangioma
Infantile haemangioma was diagnosed by clinical evalua-
tion of age, and appearance and development of the
lesion, combined with ultrasonography or magnetic
resonance imaging (MRI) or color Doppler. Attention
was paid to differentiate haemagioma from vascular
malformation. All of the haemangiomas were located at
head, face or neck.
Application of bleomycin A5
The sclerosing mixture is composed of 5 ml 2% lido-
caine, 5 mg dexameson and 8 mg bleomycin A5. The
mixture was multiplely injected with 5-gauge needle
through the places close to the lesion for avoiding
bleeding until the hemangioma became pale. The bleo-
mycin was injected in a radial fashion. The dosage was
given according to the age of the patient and size of the
lesion. Generally, lesion of 2 cm diameter was given 1
mg bleomycin A5 per time and total 5 times would be
enough. For the patient with bigger haemangioma, the
amount of bleomycin A5 was usually less than 3 mg per
time. The amount of bleomycin A5 is usually less than
0.5 mg when the baby is less than 3 month, the amount
less than 1.5 mg before 6 months, less than 2 mg before
1 year old, less than 2.5 mg before 2 years old [Table 1].
The interval of injection was 3 to 4 weeks with total
times less than 7 times during one therapeutic period.
Another treatment periods started 3 months later if
further treatment was necessary. The total quantity of
bleomycin A5 for a child should be less than 40 mg in
one treatment periods.
Prednisone treatment was used according to the
patient’s age and the size of the lesion. If the age was
less than 7 months, prednisone was given by mouth(2-5
mg/kg/day, QOD, for one month). If the lesion was
more than 4 cm, prednisone treatment lasted for 2
periods. Prednisone was usually given at the third
month and the sixth month after birth.
Evaluation of the effects of bleomycin A5
The size and blood flow of the hemangioma were evalu-
ated with color ultrasonography every two months. The
change of the lesion skin color and scar forming was
also evaluated every two months.
Satisfaction of family members was determined
according to the final appearance of patient.
Results
The effects of bleomycin A5 on infantile haemangiomas
were divided into three degrees and sumarised in table
2. Degree I: the lesion involuted completely with normal
function. The color of the lesion skin and muccal were
also recovered to normal. Degree II: the lesion involuted
completely but scar formed or the color was not recov-
ered to normal. Degree III: the lesion was only partially
involuted.
As sumarised in Table 2, all the haemangiomas invo-
luted completely after treated with bloemycin A5. How-
ever, the haemangiomas less than 2 cm were easier
recovered to normal skin color with less scar forming,
comparing with the haemangiomas more than 2 cm.
Size/colour and blood flow changes. The lesion usually
begins to decrease after the third time, the height of
lesion first decreases with colour fading, then the dia-
meter decreases after 4-5 times injection. Blood flow
declines after 4-5 times injection too, but blood flow sig-
nal disappears earlier than colour (usually after 5-6
times injection whose diameter is less than 4 cm).
Figure 1 Age of first consultation.
Figure 2 Distribution of hemangioma size.
Table 1 The dosage according to lesion size and patient’s
age
Lesion size(diameter, cm) Age(month)
0-2 2-4 4-6 > 6 < 3 < 6 < 12 < 24
Amount
(mg)
1 2 3 > 3 0.5 1.5 2 2.5
Luo and Zhao Head & Face Medicine 2011, 7:11
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The percentage of satisfaction was also higher in the
patients with haemangioma less than 6 cm, but percen-
tage of of dissatisfaction was higher with haemangioma
more than 6 cm [Table 2]. Typical cases were given in
Figures 3, 4, 5, 6, 7 and 8.
Complications included edema, ulceration, gastroin-
tenstinal side effects, and others [Table 3]. Edema
emerged about 4 hours after the injection and reached
maximal degree about two days later. The edema gener-
ally disappeared about 15 days later. Ulceration hap-
pened in the surface of the haemangiomas and healed
mostly in 15 days with scar forming.
Gastrointenstinal side effects included nausea and lack
of appetite and often happened one day later, disap-
peared three days later.
Discussion
Infantile haemangiomas are usually small lesions and
can involute spontaneously. However, some infantile
haemangiomas will not involute and even develope to
Figure 3 This boy presented at 40 days of age with a
hemangioma in the left parotid area. Bleomycin A5 was given
once every 4 weeks for a total of 7 treatments.
Figure 4 The hemangioma had completely involuted one year
later. The overall response was Scale II.
Figure 5 This girl had a hemangioma at the center of her face
that involved the nose, right eyelid, and bilateral medial
canthi.
Table 2 Lesion’s involution and family’s satisfaction
Size(cm) 0-2 2-4 4-6 Above 6
Degrees I II III I II III I II III I II III
Cases 21 14 0 8 15 0 5 12 0 0 7 0
Percentage(%) 60 40 34.8 65.2 28.8 71.2 100
Satisfaction(%) 88.6 82.6 88.2 57.1
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destroy the organ founction with deformity. Clinically
there is no good method to predict the process of infan-
tile haemangioma. It is still controversial whether the
infantile haemangioma should be treated or not.
According to our clinical experience, we suggested that
infantile haemangioma should be treated at early stage
to prevent the haemangioma from proliferation.
There are several well-established treatments for
infantile haemangioma. The major options include corti-
costeroids (either intralesional or systemic corticoster-
iods), interferon-a, laser therapy, cryotherapy, and
surgical excision [7-10]. We used Bleomycin A5 as scler-
osesing agent to modulate angiogenesis of the infantile
haemangiomas, and achieved good effects.
Sometime we used bleomycin A5 accompanying by
prednisone. We observed that infantile haemangioma
usually proliferated rapidly before the postnatal seventh
month, especially in the third and sixth month.
Although bleomycin A5 can inhibit the haemangioma
proliferation effectively, but the dosage was restricted,
therefore the drug quantity given in one time may be
deficient for big haemangioma(> 4 cm). Another clinical
phenomenon which should be paid attention to was that
the rapid proliferation in a few of infantile haemangioma
can’t be controlled at once after bleomycin injection. All
above were the reasons that we sometime used predni-
sone as adjuvant therapy. This is different from other
Figure 6 The hemangioma involuted one year and five months
after bleomycin treatment. The overall response was Scale II.
Figure 7 A large hemangioma was present on the left face,
involving the eyelid, nose, and upper lip. Bleomycin A5 was given
once a month for 7 months. Four months later, treatment was
resumed again. The total treatment period was 2 years and 4 months.
Figure 8 Three years later, the hemangioma had completely
involuted, with few scars, the overall was Scale I.
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scholars [1-3]. All infantile haemangioma were cured
through this way in our hospital.
The pathogenesis of haemangioma is due to the prolif-
eration of vascular endothelial cells. Bleomycin acts on S
stage of cell cycle to snip DNA chain during cell mitosis
and disturb the cell proliferation. Therefore, the effects
of Bleomycin A5 on infantile haemangioma is believed
to destroy the proliferation of vascular endothelial cells.
The onset of involution is usually heralded by a change
in color from bright red to purple or gray after treated
with Bleomycin A5 for several times. Small haemangio-
mas (< 2 cm) would be effectively treated within 5 times
of injection with total quantity less than 10 mg of Bleo-
mycin A5. However, big haemangioma (> 4 cm) usually
needs more than 8 times of injection with total quantity
more than 16 mg of Bleomycin A5. The therapeutic
effect was related to the lesion size and the dosage of
bleomycin A5 being given.
Some complications occurred during the treatment.
Edema was the most common complication, followed by
ulceration. However, serious side effects would rarely
occur due to the lower dosage in this treatement.
Conclusively, we reviewed the effects of bleomycin A5
on 82 cases of infantile haemangiomas and found that
all the haemangiomas involuted completely after treated
with bloemycin A5 with better recovery of skin color
and less scar forming in small haemangiomas. The
results suggested that infantile haemangioma could be
effectively treated with bleomycin A5 without serious
side effects.
Consent
Written informed consent was obtained from the patient
for publication of this case report and accompanying
images. A copy of the written consent is available for
review by the Editor-in-Chief of this journal.
Authors’ contributions
QFL conceptualized the paper. QFL and FYZ drafted and edited the
manuscript, the treatment were performed by them too. All authors have
read and approved the final manuscript.
Competing interests
The authors declare that they have no competing interests.
Received: 15 March 2009 Accepted: 7 July 2011 Published: 7 July 2011
References
1. Pienaar Conrad, Graham Roger, Geldenhuys Stuart, et al: Intralesional
Bleomycin for the Treatment of Hemangiomas. Plast Reconstr Surg 2006,
117:221-226.
2. Omidvari S, Nezakatgoo N, Ahmadloo N, et al: Role of intralesional
bleomycin in the treatment of complicated hemangiomas: prospective
clinical study. Dermatol-Surg 2005, 31(5):499-501.
3. Muir T, Kirsten M, Fourie P, et al: Intralesional bleomycin injection (IBI)
treatment for haemangiomasand congenital vascular malformations.
Pediatr Surg Int 2004, 19:766-773.
4. Ming Li-June: Structure and Function of Metalloantibiotics. Medicinal
Research Reviews 2003, 23(6):697-762.
5. Marek J: Ostrowski An Assessment of the Long-Term Results of
Controlling the Reaccumulation of Malignant Effusions Using lntracavity
Bleomycin. Cancer 1986, 57:721-727.
6. Shastri Sachidananda, Slayton ERobert, Wolter Janet, Perlia PCharles, et al:
Clinical study with bleomycin. Cancer 1971, 28:1142-1146.
7. Jensen JL, Goel R, Venner PM: The Effect of Corticosteroid Administration
on Bleomycin Lung Toxicity. Cancer 1990, 65:1921-1927.
8. Poetke Margitta, Philipp MCarsten, Urban Peter, Berlien Hans-Peter: Laser
Therapy of Haemangiomas and Vascular Malformations-Techniques and
Strategies. Medical Laser Application 2004, 19(1):32-44.
9. Hohenleutner Silvia, Badur-Ganter Elke, Landthaler Michael,
Hohenleutner Ulrich: Long-Term Results in the Treatment of Childhood
Hemangioma With the Flashlamp-Pumped Pulsed Dye Laser: An
Evaluation of 617 Cases. Lasers in Surgery and Medicine 2001, 28:273-277.
10. Al-Sebeih Khalid, Manoukian John: Systemic steroids for the management
of obstructive subglottic haemangioma. The Journal of Otolaryngology
2000, 29(6):361-366.
doi:10.1186/1746-160X-7-11
Cite this article as: Luo and Zhao: The effects of Bleomycin A5 on
infantile maxillofacial haemangioma. Head & Face Medicine 2011 7:11.
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Table 3 Complications during the usage of Bleomycin A5
Complication Edema Gastrointenstinal Ulceration Pneumonic fibrosis Others
Cases 82 5 6 0 0
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