Page 4 - CUA Best Practice Report: Pediatric hemorrhagic cystitis

Hannick & Koyle

Non-invasive treatment
al conducted a study of patients receiving cyclophospha-
mide conditioning prior to allogeneic BMT who were treated
with CBI and compared to historical controls who did not
27
receive CBI. The treatment group received CBI with nor- Antivirals
mal saline at 300 ml/hour via a three-way Foley catheter 12
hours before their first dose of cyclophosphamide through Given the aforementioned prevalence of viral sources of
until 48 hours after their last dose of cyclophosphamide, HC, some have recommended following BK virus titers in
at which point the catheter was removed. The incidence of urine and blood using DNA PCR assays during the course
19
HC in the treatment group was 32.5% compared to 50% of conditioning for BMT/SCT. Alternatively, at the onset of
in the control group (p=0.11), and there was no significant HC, viral cultures and viral loads can be measured to target
difference of the grades of HC. There was, however, a shorter therapeutic intervention. The antiviral cidofovir has become
duration of HC and shorter hospitalization in the treatment the mainstay of treatment for polyomaviruses, such as BKV
group, was well as a lower incidence of late-onset HC (7.7% and JCV, and adenovirus, though its route of administra-
in CBI group, 45% in control group; p=0.009). Though no tion, and dosage are quite varied in the literature. Given
comparative studies have evaluated its effectiveness alone, its potential nephrotoxicity and potential pre-existing renal
using similar rationale to that of CBI, many conditioning compromise in this patient population, lower doses (0.25‒1
protocols incorporate the use of IV hyperhydration (4‒5 L mg/kg/week vs. traditional 3‒5 mg/kg/week), administration
D5 with 0.45% normal saline [NS] with 20 mEq KCl/day, through an intravesical route via urethral catheter (invasive),
starting 24 hours prior to infusion of cyclophosphamide) or combination with probenecid have all been proposed to
and forced diuresis (as needed to maintain urine output of reduce potential renal injury. 30-32 Other antivirals, lefluno-
150‒200 ml/hour) in attempts to dilute potential damaging mide to treat BKV and ribavirin to treat adenovirus, have
therapy byproducts. 2,28 also been studied in pediatric patients with virus-induced
The addition of mesna to therapy during conditioning HC, but rigorous trials assessing their efficacy in this patient
targets the acrolein metabolite of cyclophosphamide through population are lacking. 33,34
binding with mesna’s sulfhydryl group and consequent deac- Recommendation: In patients with HC proven to be due
tivation of acrolein. In a prospective, controlled study, Jiang to a virus on urine culture or urine PCR, targeted treat-
et al compared intermittent to continuous intravenous (IV) ment with IV or intravesical antivirals is recommended as
11
mesna during cyclophosphamide conditioning. Patients in a relatively low-risk treatment (Level 3 evidence, Grade C
the continuous treatment group had significantly less HC recommendation).
occurrences at both 30 and 60 days (continuous: 30 days
– 0%, 60 days – 5.88%; intermittent: 30 days – 34.4%, 60 Pentosan polysulfate (PPS)
days – 40.6; p<0.002 for both).
Control of the dysuria or bladder spasms that may be The use of PPS has been primarily studied in interstitial
associated with HC and/or Foley catheterization for its cystitis. As a semisynthetic glycosaminoglycan, its proposed
prevention and/or treatment is routine. Options for pain mechanism of action is through adherence to the bladder
management include treatment through the use of vari- wall glycosaminoglycan layer and replacement of already
ous short- and long-acting narcotics, (i.e., morphine and damaged areas in order to protect the bladder from irritants
derivatives), anticholinergics (i.e., solifenacin, oxybutynin, such as urine, bacteria, and other toxic substances. Duthie
6
and tolterodine), penazopyridine, and intravesical lidocaine/ et al tested the application of PPS to the pediatric post-
bupivacaine. 21,28,29 Many of these patients will also experi- BMT HC population through the introduction of a protocol
ence marked myelosuppression, therefore, close monitoring for HC management and retrospectively compared this to
35
and replacement of red blood cells, platelets, and plasma is historical controls. Once HC was diagnosed, protocol
required to ensure the safe and successful resolution of HC. 28 patients were hydrated and treated with analgesia and oral
Recommendation: Routine history and physical with PPS 100 mg three times daily. Bladder catheterization was
imaging should be performed to confirm the etiology of avoided, escalating from in/out to CBI if patients had repeat
HC at onset. All patients undergoing chemotherapeutic clot retention and cystoscopy with clot evacuation in refrac-
conditioning prior to allogeneic BMT/SCT should receive tory bleeding. The authors noted that the diagnosis of HC
preventative hyperhydration, CBI, and mesna, as well as, was made significantly quicker with the introduction of the
supportive analgesia with systemic and targeted medica- protocol (39 vs. 76 days; p<0.01) and transfusions of blood
tions at the onset of HC with symptoms (Level 3 evidence, and platelets were significantly reduced in the protocol
Grade C recommendation). group. No side effects of the drug were noted. Both groups
had similar duration of HC (protocol 32 days vs. control
36 days; p=0.84), although 4/5 controls died with active

E328 CUAJ • November 2019 • Volume 13, Issue 11