Paradoxical rising cytomegalovirus antigenemia during preemptive ganciclovir therapy in hematopoietic stem cell transplant recipients: incidence, risk factors, and clinical outcomes.
Preemptive ganciclovir (GCV) therapy is adopted increasingly in hematopoietic stem cell transplant (HCT) recipients, but occasional cases of increasing cytomegalovirus (CMV) antigenemia levels occur during preemptive GCV therapy. This prospective study investigated the incidence, risk factors, and clinical outcomes of paradoxical responses during GCV therapy. Adult patients receiving allogeneic HCTs during a 24-month period were enrolled. Patients were prospectively monitored for CMV antigenemia once a week until 3 months after engraftment. Paradoxical responders were defined as patients exhibiting CMV antigenemia levels elevated from the baseline after the first week of preemptive GCV therapy. Of 252 HCT recipients, 97 (38%) received preemptive GCV therapy due to CMV infection. Of these 97 patients, 23 (24%) were classified as paradoxical responders. Risk factors for paradoxical response were a low white blood cell (WBC) count (P = 0.02) and a prolonged duration of CMV antigenemia (P = 0.04) before preemptive therapy. There were no significant differences in rates of successful viral clearance and secondary episodes of CMV infection between paradoxical responders (87% [20/23] and 26% [6/23]) and nonparadoxical responders (95% [70/74] and 23% [17/74], respectively). However, breakthrough CMV disease during preemptive GCV therapy was significantly more frequent in paradoxical responders (17% [4/23]) than in nonparadoxical responders (3% [2/74], P = 0.03). Paradoxical responses occurred in one-quarter of the HCT recipients receiving preemptive GCV therapy. A low WBC count and a long duration of CMV antigenemia before GCV therapy were associated with paradoxical responses, and breakthrough CMV disease during preemptive GCV therapy occurred more frequently in paradoxical responders.
Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Pungnap-dong, Songpa-gu, Seoul 138-736, Republic of Korea.
So-Youn
SY
Park
Sang-Oh
SO
Lee
Sang-Ho
SH
Choi
Yang Soo
YS
Kim
Jun Hee
JH
Woo
Heungsup
H
Sung
Mi-Na
MN
Kim
Dae-Young
DY
Kim
Jung-Hee
JH
Lee
Je-Hwan
JH
Lee
Kyoo-Hyung
KH
Lee
Sung-Han
SH
Kim
D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage*; D018890:Chemoprevention / Q000379:methods; D003586:Cytomegalovirus Infections / Q000453:epidemiology* / Q000517:prevention & control*; D005260:Female; D015774:Ganciclovir / Q000008:administration & dosage*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors; D016896:Treatment Outcome; D014766:Viremia / Q000453:epidemiology* / Q000517:prevention & control*; D055815:Young Adult
D000998:Antiviral Agents; D015774:Ganciclovir