The clinical and financial burden of pre-emptive management of cytomegalovirus disease after allogeneic stem cell transplantation-implications for preventative treatment approaches.
OBJECTIVE
Although cytomegalovirus (CMV) infection after allogeneic stem cell transplantation (SCT) is rarely fatal, the management of CMV by pre-emptive medication for viral reactivation has toxicity and carries a financial burden. New strategies to prevent CMV reactivation with vaccines and antiviral T cells may represent an advance over pre-emptive strategies but have yet to be justified in terms of transplantation outcome and cost.


METHODS
We compared outcomes and post-transplantation treatment cost in 44 patients who never required pre-emptive CMV treatment with 90 treated patients undergoing SCT at our institute between 2006 and 2012. Eighty-one subjects received CD34+ selected myeloablative SCT, 12 umbilical cord blood transplants, and 41 T-replete non-myeloablative SCT. One hundred nineteen patients (89%) were at risk for CMV because either the donor or recipient was seropositive. Of these, 90 patients (75.6%) reactivated CMV at a median of 30 (range 8-105) days after transplantation and received antivirals.


RESULTS
There was no difference in standard transplantation risk factors between the two groups. In multivariate modeling, CMV reactivation >250 copies/mL (odds ratio = 3, P < 0.048), total duration of inpatient IV antiviral therapy (odds ratio = 1.04, P < 0.001), type of transplantation (T-deplete vs. T-replete; odds ratio = 4.65, P < 0.017) were found to be significantly associated with increased non-relapse mortality. The treated group incurred an additional cost of antiviral medication and longer hospitalization within the first 6 months after SCT of $58,000 to $74,000 per patient.


CONCLUSIONS
Our findings suggest that to prevent CMV reactivation, treatment should be given within 1 week of SCT. Preventative treatment may improve outcome and have significant cost savings.
Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
Natasha A
NA
Jain
Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
Kit
K
Lu
Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
Sawa
S
Ito
Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
Pawel
P
Muranski
Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
Christopher S
CS
Hourigan
Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
Janice
J
Haggerty
Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
Puja D
PD
Chokshi
Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
Catalina
C
Ramos
Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
Elena
E
Cho
Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
Lisa
L
Cook
Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
Richard
R
Childs
Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA. Electronic address: minoo.battiwalla@nih.gov.
Minoo
M
Battiwalla
Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
A John
AJ
Barrett
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D017281:Cost of Illness; D003587:Cytomegalovirus / Q000235:genetics* / Q000472:pathogenicity; D003586:Cytomegalovirus Infections / Q000191:economics / Q000473:pathology* / Q000821:virology; D005260:Female; D019337:Hematologic Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000191:economics; D006801:Humans; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology / Q000821:virology; D014019:Tissue Donors; D014184:Transplantation, Homologous / Q000009:adverse effects* / Q000191:economics; D014775:Virus Activation / Q000235:genetics
CMV reactivation; antiviral cellular therapy; economic cost; pre-emptive therapy