High efficacy and low toxicity of short-course oral valganciclovir as pre-emptive therapy for hematopoietic stem cell transplant cytomegalovirus infection.
BACKGROUND
Cytomegalovirus (CMV) infection is a major infectious complication post-allogeneic hematopoietic stem cell transplantation (HSCT). CMV seropositivity in Eastern Mediterranean and certain Asian countries is reported to be close to 100%; hence, the need for effective pre-emptive treatment strategy that has low toxicity. Valganciclovir (VGC) is a prodrug of ganciclovir with high bioavailability.


METHODS
HSCT patients with documented CMV infection (as defined by positive CMV antigenemia) were treated as outpatients with VGC at a starting dose of 900 mg twice daily for 1 week. Those who were antigenemia negative after one week received 900 mg once daily for another week and treatment was subsequently discontinued. Those who were positive after one week of therapy continued on the twice-daily treatment schedule for another week and changed to a daily schedule once they converted to antigenemia negativity.


RESULTS
From January 2004 to December 2007, 47 HSCT patients received preemptive treatment with VGC for 61 episodes of CMV infection. The antigenemia range was 1 to 700 infected cells/slide. Complete responses were observed in 92% and 97% after the 1st and 2nd week of treatment, respectively. Three percent of the episodes were considered refractory, requiring alternative therapy. No CMV disease was observed in this cohort.


CONCLUSIONS
Neutropenia was the main observed toxicity, requiring granulocyte-colony stimulating factor in 8 episodes. Outpatient treatment of CMV infection with "short-course oral VGC" given as a one-week twice-daily treatment and one week once daily maintenance is a highly effective therapy with minimal toxicity. These results require validation in a larger, randomized study.
Saleh
A J M
AJ
King Faisal Cancer Centre, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. asaleh@kfshrc.edu.sa
Al Mohareb
Fahad
F
Al Rabiah
Fahad
F
Chaudhri
Naeem
N
Al Sharif
Fahad
F
Al Zahrani
Hazzaa
H
Mohamed
Said Yousuf
SY
Patel
Moosa
M
Rasheed
Walid
W
Nurgat
Zubeir
Z
Bakr
Mohammad
M
Ahmed
Shad
S
Zaidi
Syed
S
Nasser
Amr
A
Ibrahim
Khaled
K
Al Abdely
Hail
H
Aljurf
Mahmoud
M
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000956:Antigens, Viral / Q000097:blood; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D003587:Cytomegalovirus / Q000187:drug effects / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000188:drug therapy* / Q000209:etiology; D004334:Drug Administration Schedule; D005260:Female; D015774:Ganciclovir / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D016896:Treatment Outcome; D000077562:Valganciclovir; D055815:Young Adult
D000956:Antigens, Viral; D000998:Antiviral Agents; D000077562:Valganciclovir; D015774:Ganciclovir