Cidofovir for the treatment of adenovirus disease in HSCT patients
| Author (year of publication) . | No. of patients . | P/R . | Indication . | Drug therapy . | Nephrotoxicity, n % . | Success AdV clearance, n % . | Mortality, n (%) or direct AdV-related mortality, n (%) . |
|---|---|---|---|---|---|---|---|
| Preemptive treatment | Preemptive treatment | ||||||
| Anderson (2008) | 7 Children | P | 7 patients with AdV isolation from plasma, or from 2 other sites evaluated by PCR | CDV 1 mg/kg intravenously 3 times a week | 0 (0) | 2 (28) | 2 (29) |
| 5 still had isolation of AdV from any of the peripheral sites after CDV discontinuation, all resolved spontaneously. | 0 (0) | ||||||
| Bhadri (2009) | 20 Children | R | Proven AdV in stool, urine, NPA, CSF. | Induction with 5 mg/kg intravenously, followed by 3 mg/kg | 7 (35) | 17 (85) | 14 (70) |
| Routine stool screening rapid culture, antigen detection | When prolonged treatment was needed 1 mg/kg 3 times a week | 2 (10) | |||||
| Screening for AdV in other sites as clinically indicated | |||||||
| Greil et al (2006) | 10 Children | R | AdV detection in 10 of 34 pediatric patients treated with ribavirin prophylaxis | Ribavirin prophylaxis | No data | No data | 1 (10) |
| CDV preemptive | 0 (0) | ||||||
| Ljungman (2003) | 16 Adults and children | R | Asymptomatic patients (n = 16) of a total of 45 patients with any detection of AdV from stool, upper airway specimens, blood, urine (detection by culture, antigen detection, PCR) | CDV 5 mg/kg intravenously weekly (n = 39) | No data for this group; overall in 45 patients, 17 (38%) | (75) | 6 (37) |
| 1-4 mg/kg (n = 6) | 2 (13) | ||||||
| Yusuf (2006) | 14 Children | R | 14 asymptomatic pediatric patients (of a total number of 57 patients), positive AdV detection by PCR | CDV 5 mg/kg intravenously weekly, for 2 weeks, followed by once every 2 weeks until viral clearance with 3 negative samples | 0 | (100) | No data for this group |
| Median 5 doses (range, 1-22) | None of which developed reactivation | 29 of 57 (51) for the whole group | |||||
| 1 of 57 (8) | |||||||
| Therapeutic treatment | Therapeutic treatment | ||||||
| Robin (2007) | 25 Adults and children | R | Disseminated AdV disease | CDV 5 mg/kg intravenously weekly | No data | 6 (24) | 21 (84) |
| Symeonidis (2006) | 11 Adults and children | R | Positive AdV cultures and severe or persistent symptoms | CDV 5 mg/kg intravenously weekly | 2 (18) | No data | 6 (54) |
| OR | 6 (54) | ||||||
| CDV 1 mg/kg every other day | |||||||
| Ouachee-Chardin (2004) | 16 children | R | AdV disease | CDV 3-5 mg/kg intravenously weekly | 5 (31) reversible tubulopathy | 14 (87) | 3 (18) |
| PCR for detection of AdV | 2 (13) | ||||||
| Yusuf (2006) | 43 Children | R | 43 Patients with clinical symptoms attributable to AdV infection | CDV 5 mg/kg intravenously weekly for 2 weeks, followed by once every 2 weeks until viral clearance with 3 negative samples | 0 | 42 (97) | No data for this group |
| AdV detection by PCR (of a total number of 57 patients with positive AdV PCR) | Median 5 doses (range, 1-22) | 29/57 (51) for the whole group | |||||
| 1 of 57 (8) | |||||||
| Hoffman (2001) | 8 Children | P | Of 17 patients with positive AdV cultures, 8 were enrolled in phase 2 trial of CDV treatment | CDV 1 mg/kg intravenously 3 times a week | 1 (13) | 8 (100) | 2 (25) |
| Detection with shell vial culture method | Not leading to discontinuation | 0 (0) | |||||
| Ljungman (2003) | 29 Adults and children | R | Patients with probable and definite AdV disease (n = 29) of a total of 45 patients with any detection of AdV from stool, upper airway specimens, blood, urine (detection by culture, antigen detection, PCR) | CDV 5 mg/kg intravenously weekly (n = 39) | No data of this group. | 20 (69) | 10 (34) |
| 1-4 mg/kg (n = 6) | Overall in 45 patients: 14 (31%) | 5 (17) | |||||
| Muller (2005) | 10 Children | R | AdV isolation from > 1 site and clinical symptoms, or isolation from 1 site with severe clinical symptoms | CDV 5 mg/kg intravenously weekly during 6 weeks, followed by once every 2 weeks for total of 9 doses | 3 (30) (with > 50% serum creatinine elevation) | 9 (90), 1 required additional CDV therapy to clear the virus | 0 (0) |
| Kampmann (2005) | 11 Children | R | Patients in whom AdV was detected (n = 26) were on ribavirin. In case of persistent adenoviremia and AdV disease CDV was started (n = 11). | CDV 5 mg/kg intravenously weekly for 2 weeks, followed by 5 mg/kg every 2 weeks | ? | No data in this group | 9 (81) |
| In case of persistent adenoviremia and AdV disease CDV was started (n = 11). | 5 (46) | ||||||
| Nagafuji (2004) | 16 Adults | P | Patients after HSCT with hemorrhagic cystitis and a urine sample positive for viral culture, Adv PCR and immunochromatograph | CDV 1 mg/kg intravenously 3 times a week, for 3 weeks | 3 (19) | 12 (75) | 2 (13) |
| Author (year of publication) . | No. of patients . | P/R . | Indication . | Drug therapy . | Nephrotoxicity, n % . | Success AdV clearance, n % . | Mortality, n (%) or direct AdV-related mortality, n (%) . |
|---|---|---|---|---|---|---|---|
| Preemptive treatment | Preemptive treatment | ||||||
| Anderson (2008) | 7 Children | P | 7 patients with AdV isolation from plasma, or from 2 other sites evaluated by PCR | CDV 1 mg/kg intravenously 3 times a week | 0 (0) | 2 (28) | 2 (29) |
| 5 still had isolation of AdV from any of the peripheral sites after CDV discontinuation, all resolved spontaneously. | 0 (0) | ||||||
| Bhadri (2009) | 20 Children | R | Proven AdV in stool, urine, NPA, CSF. | Induction with 5 mg/kg intravenously, followed by 3 mg/kg | 7 (35) | 17 (85) | 14 (70) |
| Routine stool screening rapid culture, antigen detection | When prolonged treatment was needed 1 mg/kg 3 times a week | 2 (10) | |||||
| Screening for AdV in other sites as clinically indicated | |||||||
| Greil et al (2006) | 10 Children | R | AdV detection in 10 of 34 pediatric patients treated with ribavirin prophylaxis | Ribavirin prophylaxis | No data | No data | 1 (10) |
| CDV preemptive | 0 (0) | ||||||
| Ljungman (2003) | 16 Adults and children | R | Asymptomatic patients (n = 16) of a total of 45 patients with any detection of AdV from stool, upper airway specimens, blood, urine (detection by culture, antigen detection, PCR) | CDV 5 mg/kg intravenously weekly (n = 39) | No data for this group; overall in 45 patients, 17 (38%) | (75) | 6 (37) |
| 1-4 mg/kg (n = 6) | 2 (13) | ||||||
| Yusuf (2006) | 14 Children | R | 14 asymptomatic pediatric patients (of a total number of 57 patients), positive AdV detection by PCR | CDV 5 mg/kg intravenously weekly, for 2 weeks, followed by once every 2 weeks until viral clearance with 3 negative samples | 0 | (100) | No data for this group |
| Median 5 doses (range, 1-22) | None of which developed reactivation | 29 of 57 (51) for the whole group | |||||
| 1 of 57 (8) | |||||||
| Therapeutic treatment | Therapeutic treatment | ||||||
| Robin (2007) | 25 Adults and children | R | Disseminated AdV disease | CDV 5 mg/kg intravenously weekly | No data | 6 (24) | 21 (84) |
| Symeonidis (2006) | 11 Adults and children | R | Positive AdV cultures and severe or persistent symptoms | CDV 5 mg/kg intravenously weekly | 2 (18) | No data | 6 (54) |
| OR | 6 (54) | ||||||
| CDV 1 mg/kg every other day | |||||||
| Ouachee-Chardin (2004) | 16 children | R | AdV disease | CDV 3-5 mg/kg intravenously weekly | 5 (31) reversible tubulopathy | 14 (87) | 3 (18) |
| PCR for detection of AdV | 2 (13) | ||||||
| Yusuf (2006) | 43 Children | R | 43 Patients with clinical symptoms attributable to AdV infection | CDV 5 mg/kg intravenously weekly for 2 weeks, followed by once every 2 weeks until viral clearance with 3 negative samples | 0 | 42 (97) | No data for this group |
| AdV detection by PCR (of a total number of 57 patients with positive AdV PCR) | Median 5 doses (range, 1-22) | 29/57 (51) for the whole group | |||||
| 1 of 57 (8) | |||||||
| Hoffman (2001) | 8 Children | P | Of 17 patients with positive AdV cultures, 8 were enrolled in phase 2 trial of CDV treatment | CDV 1 mg/kg intravenously 3 times a week | 1 (13) | 8 (100) | 2 (25) |
| Detection with shell vial culture method | Not leading to discontinuation | 0 (0) | |||||
| Ljungman (2003) | 29 Adults and children | R | Patients with probable and definite AdV disease (n = 29) of a total of 45 patients with any detection of AdV from stool, upper airway specimens, blood, urine (detection by culture, antigen detection, PCR) | CDV 5 mg/kg intravenously weekly (n = 39) | No data of this group. | 20 (69) | 10 (34) |
| 1-4 mg/kg (n = 6) | Overall in 45 patients: 14 (31%) | 5 (17) | |||||
| Muller (2005) | 10 Children | R | AdV isolation from > 1 site and clinical symptoms, or isolation from 1 site with severe clinical symptoms | CDV 5 mg/kg intravenously weekly during 6 weeks, followed by once every 2 weeks for total of 9 doses | 3 (30) (with > 50% serum creatinine elevation) | 9 (90), 1 required additional CDV therapy to clear the virus | 0 (0) |
| Kampmann (2005) | 11 Children | R | Patients in whom AdV was detected (n = 26) were on ribavirin. In case of persistent adenoviremia and AdV disease CDV was started (n = 11). | CDV 5 mg/kg intravenously weekly for 2 weeks, followed by 5 mg/kg every 2 weeks | ? | No data in this group | 9 (81) |
| In case of persistent adenoviremia and AdV disease CDV was started (n = 11). | 5 (46) | ||||||
| Nagafuji (2004) | 16 Adults | P | Patients after HSCT with hemorrhagic cystitis and a urine sample positive for viral culture, Adv PCR and immunochromatograph | CDV 1 mg/kg intravenously 3 times a week, for 3 weeks | 3 (19) | 12 (75) | 2 (13) |
Listed are all clinical studies that used cidofovir in patients who received HSCT either for preemptive treatment when symptoms are not yet present or for therapeutic treatment when disease symptoms are present. Only studies with n > 5 were presented.
P indicates prospective study; R, retrospective study; AdV, adenovirus; CDV, cidofovir; NPA, nasopharyngeal aspirate; CSF, cerebrospinal fluid; PCR, polymerase chain reaction.