Vol.2, No.5, 298-301 (2013) Case Reports in Clinical Medicine
After allogenic bone marrow transplantation agent of
hemorrhagic cystitis: BK virus*
Berber Ilhami1#, Koroglu Mustafa1, Erkurt Mehmet Ali1, Oguz Fatih2, Altint as Ramazan2,
Kaya Emin1, Kuku Irfan1, Ulutas Ozkan3
1Department of Hematology, Faculty of Medicine, Inonu University, Malatya, Turkey;
#Corresponding Author: drilhamiberber@hotmail.com
2Department of Urology, Faculty of Medicine, Inonu University, Malatya, Turkey
3Department of Nephrology, Faculty of Medicine, Inonu University, Malatya, Turkey
Received 5 June 2013; revised 11 July 2013; accepted 20 July 2013
Copyright © 2013 Berber Ilhami et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Hemorrhagic cystitis is a common and in its
severe form potentially life threatening compli-
cation of hematopoietic stem cell transplanta-
tion. Hemorrhagic cystitis is defined as a diffuse
inflammatory condition of the urinary bladder
due to an infectious or noninfectious etiology
resulting in bleeding from the bladder mucosa.
Hemorrhagic cystitis is characterized by lower
urinary tract symptoms including dy suria, hema-
turia and h emorrhag e. The mos t common cause is
a bacterial infection that usuall y responds prom-
ptly to treatment. But chronic and recurrent he-
morrhagic cystitis often arises from anticancer
chemotherapy or radiotherapy for the treatment
of pelvic malignancies. Infectious etiologies are
less common causes of chronic hemorrhagic
cystitis except in immunocompromised hosts
like bone marrow transplant recipients. Hemor-
rhagic cystitis is a significant complication of
bone marrow transplantation which influences
economic and survival outcome. Hemorrhagic
cystitis can be divided into two classes accord-
ing to onset time; early and late onset time. Early-
onset hemorrhagic cystitis is commonly asso-
ciated used with chemo-radiotherapy protocols
in some of the preparatory regimens. More than
one factor is accused in the etiology of late
onset hemorrhagic cystitis. Here, we present a
patient whose hematuria started after 54 days
from allogeneic stem cell transplantation.
Keywords: Allogenic Bone Marrow Transplantation;
Hemorrhagic Cysti tis; BK V irus
Hemorrhagic cystitis is described as a diffuse in-
flammatory condition of the urinary bladder due to an
infectious or noninfectious etiology resulting in bleeding
from the bladder mucosa. Hemorrhagic cystitis is diffe-
rentiated into two types according to onset time; early
and late onset hemorrhagic cystitis [1].
Early-onset hemorrhagic cystitis commonly associates
with chemo-radiotherapy used in the preparation regi-
mens. Especially, hemorrhagic cystitis emerges as a re-
sult of high dose cyclophosphamide an d ifosfamide treat-
ments. The dose of cyclophosphamide is associated with
the risk of hemorrhagic cystitis. If prophylaxis is not
used for hemorrhagic cystitis in cases with hematopoietic
stem cell transplantation, the risk of hemorrhagic cystitis
has increased. Hematuria is the most frequently occurred
after two weeks of preparation regimen. On the other
hand, hemorrhagic cystitis can start immediately or three
months later after application of cyclophosphamide. Risk
is increased in patients who had pelvic irradiation and
busulfan treatment. Allogeneic transplant patients and
elderly patients have an additional risk in terms of hem-
orrhagic cystitis [2].
Multiple factors are accused in the etiology of late-
onset hemorrhagic cystitis. Generally, this type of hem-
orrhagic cystitis occurs after weeks or months from trans-
plantation. A history of hemorrhagic cystitis attack is the
most important risk factor for another attack. Viruses and
graft versus host disease (GVHD) are also accused in the
etiology of hemorrhagic cystitis. The BK polyoma virus,
adenovirus, cytomegalovirus (CMV), JC virus, Epstein
Barr virus (EBV) and herpes virus have been implicated
in the etiology of hemorrhagic cystitis. Suitable hosts for
*The authors declare that they have no competing i nt e rests.
Copyright © 2013 SciRes. OPEN ACCESS
B. Ilhami et al. / Case Reports in Clinical Medicine 2 (2013) 298-301 299
these viruses are immunosuppressed patients. GVHD and
hemorrhagic cystitis are another issue discussed in the
literature [1].
The BK virus is a member of the polyoma virus family.
BK virus is highly prevalent in the population and is
thought to remain dormant and asymptomatic in the kid-
ney and other organs after the initial infection. Wh en the
immune system is compromised, as in persons undergo-
ing chemotherapy after bone marrow, stem cell and solid
organ transplantation, the virus gets reactivated leading
to cystitis. BK virus has been reported to cause hemorr-
hagic cystitis in 5.7% to 7.7% of bone marrow transplant
recipients. Early diagnosis and treatment of viral cystitis
may prevent significant morbidity of hemorrhagic cysti-
tis. The diagnosis is based on molecular techniques and
real-time polymerase chain reaction (PCR), which allows
quantification of viral load is often the method of choice
[3]. Although no drug is yet licensed fo r use in BK virus
infection, cidofovir is becoming the drug of choice in
viral hemorrhagic cystitis in immunosupressed patients
because it is active against the most common viral patho-
gens. Leflunomide has been shown to significantly re-
duce BK viral load in blood an d urine in renal transplant
patients with biopsy proven BK nephropathy [4]. Cipro-
floxacin may have a prophylactic role in preventing BK
viral cystitis in bone marrow transplant patients [5]. Hy-
perbaric oxygen in the treatment of refractory hemor-
rhagic cystitis can be used successfully in patients [6].
Here, we present a case of hemorrhagic cystitis due to
BK virus infection in an acute myeloid leukemia patient
was treated with allogeneic stem cell transplantation.
A 40 years old female patient was diagnosed acute
myeloid leukemia and idarubicine 1 × 12 mg/m2/day (3
days), cytarabine 1 × 100 mg/m2/day (7 days) therapies
as induction and 3 cycles of high-dose cytarabine (2 × 3
g/m2/day) therapy for consolidation were given success-
fully. After these treatments, the patient was applied
seamlessly allogeneic stem cell transplantation from
HLA matched siblings with BU-CY (busulfan-cyclo-
phosphamide) protocol (busulfan 4 × 0.8 mg/kg/day (4
days), cyclophosphamide 60 mg/kg/day (2 days), mesna
90 mg/kg/day (2 days) in bone marrow transplantation
unit. Although the patient did not have hematuria before
he experienced a gross hematuria episode in fifty second
day of transplantation. Physical examination revealed
marked suprapubic tenderness. A complete blood count
revealed hemoglobin 8.8 g/dL, leukocyte 2.100/microL,
neutrophil 1.500/microL, lymphocyte 500/microL, and
platelets 22.000/microL. Peripheral blood smear was com-
patible with blood count. International normalized ratio
(INR), Activated Partial Thromboplastin Time (APTT),
and serum creatinine levels were normal. C-reactive pro-
tein concentration was moderately elevated as 3.2 mg/dL.
The red color of urine was seen only in the sediment (and
the supernatant was not red). Bacterial or fungi infection
were not seen in the cytobacteriological examination of
urine samples. Nephrolithiasis, or other bladder patholo-
gies causing of hematuria were not seen in radiographic
examinations including ult rasonography, non-cont rast com -
puted tomography of abdomen and pelvis. Medication
usage history in terms of hemorrhagic cystitis was nega-
tive. Hemocultures and urine cultu res were negative. The
patient was not using drugs like anticoagulants at this
time and patient was using treatments like cyclosporine
(2 × 150 mg/day/i.v), methyl prednisolone (1 × 120 mg/
day/i.v) and intravenous immune globulin (5 gr/day/i.v
once a weak to 100th day) for GVHD and infection pre-
vention. After excluding other causes of hematuria, urine
analysis with polymerase PCR analysis revealed positiv e
BK virus. Real-time PCR for adenoviruses was negative.
We could not analyze the other viruses. Platelet suspen-
sion was given and then platelet counts was detected
72.000/microL, but gross hematuria persisted. Erythro-
cyte suspension was transfused intermittent ly as support-
ing treatment. We stopped methyl prednisolone and re-
duced dose of cyclosporine (2 × 50 mg/day/i.v). We gave
ciprofloxacin (2 × 400 mg/day/i.v for 14 days) treatments.
Continious bladder irrigation was performed with three
way foley urethral catheter. Cystoscopy was applied and
hemorrhagic foci was cauterized by consulting with the
department of urology and nephrology clinics (Figure 1).
After one month of mentioned treatments above blood in
the urine decreased slowly. We applied control cysto-
scopy, revealing recovery of hemorrhagic foci (Figure 2),
and blood in the urin e stopped without need of an y other
treatments. Control BK virus PCR result was negative.
Hemorrhagic cystitis after allogeneic stem cell trans-
Figure 1. Cystoscopic view of
the bladder showing the wide-
spread bleeding areas on the
bladder mucosa.
Copyright © 2013 SciRes. OPEN ACCESS
B. Ilhami et al. / Case Reports in Clinical Medicine 2 (2013) 298-301
Figure 2. Cystoscopic image af-
ter one month of treatment mi-
nimal local hemorrhagic area on
the bladder mucosa.
plantation is one of the most common causes of morbi-
dity and mortality in patient with stem cell transplan-
tation. Hemorrhagic cystitis can be emerged in the early
or late phase of stem cell transplantation [1]. In our pa-
tient, hemorrhagic cystitis was seen in fifty second day
after allogeneic stem cell transplantation. The patient was
eveluated w ith X-ray, ultr asonography and n on-spiral CT
of urinary tract, urine analysis, urine culture for diag-
nosis of hemorrhagic cystitis. Thus, among the main causes
of hematuria like stone, simple infections were elimi-
nated and the patient was diagnosed late onset hemor-
rhagic cystitis.
A grading system for severity of hemorrhagic cystitis
has been proposed by Droller et al. for hemorrhagic cys-
titis [7]. We accepted our patient. Stage III (macroscopic
hematuria with small clots) hemorrhagic cystitis and we
searched for causes of late onset hemorrhagic cystitis.
A history of hemorrhagic cystitis episode is a main
risk factor for late onset hemorrhagic cystitis. In addition,
viruses (BK virus, adenovirus, and CMV) and GVHD
are accused for hemorrhagic cystitis. Our patient did not
has a history of hemorrhagic cystitis. There was no signs
like skin rash, diarrhea, and ab normal liver function tests
which could support a diagnosis of acute GVHD. We
eveluated the urine analysis with PCR method for CMV,
adenovirus and BK virus. PCR result for BK virus was
positive. The cornerstone of therapy for hemorrhagic
cystitis due to BK virus is reduction of immunosuppres-
sion. Studies showed that overall immunosupressive load
is more important than a single immunosuppressive
agent use in terms of BK virus infections [8]. In our pa-
tient we thought the cause of BK virus infection as im-
munosuppressive load and dose of cyclosporine treat-
ment was reduced to 2 × 50 mg/day/i.v.
In the literature, a large bore three-way foley urethral
catheter insertion to decompress the bladder and saline
solution irrigation of bladder is recommended as a first
step treatment. This maneuver may slow or stop the
bleeding. In some instances cystoscopic clot evacuation
may be necessary [1]. Continuous irrigation was applied
for 30 days by consulting with th e department of urology
and nephrology clinics. Cystoscopy was performed to
treat hematuria and hemorrhage foci were cauterized by
urology clinic.
Other therapeutic options include cidofovir, leflu-
nomide, intravenous immunoglobulin, and fluoroquino-
lones for BK virus infection. Cidofovir is a nucleotide
analogue of cytosine that is active against various DNA
viruses. Cidofovir may have activity against BK virus [9].
Leflunomide reduces BK viral load in blood and urine in
renal transplant patients with BK nephropathy [4]. Lim-
ited data is available concerning the efficacy of intrave-
nous immune globulin in patients with BK nephropathy
[10]. The efficacy of ciprofloxacin, was best reported in a
study of 68 hematopoietic stem cell transplantation pa-
tients. These informations support a role for ciproflox-
acin in the prevention of BK viremia [5]. Hyperbaric
oxygen in the treatment of refractory hemorrhagic cysti-
tis is used succesfully [6]. Our patient responded to re-
duce dose of immunosuppressive, ciprofloxacin treat-
ment, intravenous immune globulin, continuous irriga-
tion and cauterization.
BK virus infection must be kept when an allogeneic
stem cell transplantation patient admitted with gross he-
This report reflects the opinion of the authors and does
not represent the official position of any institution or
sponsor. IB was responsible for reviewing previous re-
search, journal hand searching, and drafting the report.
FO and RA were responsible for provision of published
trial bibliographies, and preparing photographs. MK,
MAE and OU contributed to the final draft of the manu-
script and analysis of relevant data. IK and EK was re-
sponsible for project coordination. All authors read and
approved the final manuscript.
Written informed consent was obtained from the pa-
tient’s next of kin for publication of this manuscript and
accompanying images. A copy of the written consent is
available for review by the Editor-in-Chief of this jour-
[1] Manikandan, R., Kumar, S. and Dorairajan, L.N. (2010)
Hemorrhagic cystitis: A challenge to the urologist. Indian
Copyright © 2013 SciRes. OPEN ACCESS
B. Ilhami et al. / Case Reports in Clinical Medicine 2 (2013) 298-301
Copyright © 2013 SciRes. OPEN ACCESS
Journal of Urology, 26, 159-166.
[2] Daniel, B.D., Jose, A.K. and Duncan, T.W. (2009) Pe-
diatric hemorrhagic cystitis. Journal of Pediatric Urology,
5, 254-264. doi:10.1016/j.jpurol.2009.02.199
[3] Paduch, D.A. (2007) Viral lower urinary tract infections.
Current Urology Reports, 8, 324-335.
[4] Dropulic, L.K. and Jones, R.J. (2008) Polyomavirus BK
infection in blood and marrow transplant recipients. Bone
Marr ow Transplantation, 4, 11-18.
[5] Leung, A.Y., Chan, M.T., Yuen, K.Y., et al. (2005) Cipro-
floxacin decreased polyoma BK virus load in patients
who underwent allogeneic hematopoietic stem cell trans-
plantation. Clinical Infectious Diseases, 40, 528-537.
[6] Hughes, A.J., Schwarer, A.P. and Millar, I.L. (1998)
Hyperbaric oxygen in the treatment of refractory hemor-
rhagic cystitis. Bone Marrow Transplant, 22, 585-586.
[7] Droller, M.J., Saral, R. and Santos, G. (1982) Prevention
of cyclophosphamide-induced hemorrhagic cystitis. Urol-
ogy, 20, 256-258. doi:10.1016/0090-4295(82)90633-1
[8] Saad, E.R., Bresnahan, B.A., Cohen, E.P., et al. (2008)
Successful treatment of BK viremia using reduction in
immunosuppression without antiviral therapy. Transplan-
tation, 85, 850-854. doi:10.1097/TP.0b013e318166cba8
[9] Vats, A., Shapiro, R., Singh Randhawa, P., et al. (2003)
Quantitative viral load monitoring and cidofovir therapy
for the management of BK virus-associated nephropathy
in children and adults. Transplantation, 75, 105-112.
[10] Sener, A., House, A.A., Jevnikar, A.M., et al. (2006) In-
travenous immunoglobulin as a treatment for BK virus
associated nephropathy: One-year follow-up of renal allo-
graft recipients. Transplantation, 81, 117-120.
GVHD: Graft Versus Host Disease
CMV: Cytomegalovirus
EBV: Epstein Barr Virus
PCR: Polymerase Chain Reaction
BU-CY: Busulfan-Cyclophosphamide
INR: International Normalized Ratio
APTT: Acti vated Partial Thro mbopl astin Time