The clinical and financial burden of pre-emptive management of cytomegalovirus disease after allogeneic stem cell transplantation—implications for preventative treatment approaches

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 cell...

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Published in:	Cytotherapy (Oxford, England) Vol. 16; no. 7; pp. 927 - 933
Main Authors:	Jain, Natasha A., Lu, Kit, Ito, Sawa, Muranski, Pawel, Hourigan, Christopher S., Haggerty, Janice, Chokshi, Puja D., Ramos, Catalina, Cho, Elena, Cook, Lisa, Childs, Richard, Battiwalla, Minoo, Barrett, A. John
Format:	Journal Article
Language:	English
Published:	England Elsevier Inc 01.07.2014
Subjects:	Adolescent Adult Advanced Basic Science Aged antiviral cellular therapy Child CMV reactivation Cost of Illness Cytomegalovirus - genetics Cytomegalovirus - pathogenicity Cytomegalovirus Infections - economics Cytomegalovirus Infections - pathology Cytomegalovirus Infections - virology economic cost Female Hematologic Neoplasms - mortality Hematologic Neoplasms - pathology Hematologic Neoplasms - therapy Hematopoietic Stem Cell Transplantation - adverse effects Hematopoietic Stem Cell Transplantation - economics Humans Male Middle Aged Other pre-emptive therapy Risk Factors T-Lymphocytes - immunology T-Lymphocytes - pathology T-Lymphocytes - virology Tissue Donors Transplantation, Homologous - adverse effects Transplantation, Homologous - economics Virus Activation - genetics economic cost CMV reactivation pre-emptive therapy antiviral cellular therapy
ISSN:	1465-3249, 1477-2566, 1477-2566
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Abstract	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. 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. 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. 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.
AbstractList	Abstract Background aims 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. 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. 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. 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. 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. 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.BACKGROUND AIMSAlthough 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.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.METHODSWe 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.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.RESULTSThere 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.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.CONCLUSIONSOur 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.
Author	Muranski, Pawel Hourigan, Christopher S. Ramos, Catalina Haggerty, Janice Lu, Kit Cho, Elena Battiwalla, Minoo Childs, Richard Ito, Sawa Jain, Natasha A. Barrett, A. John Cook, Lisa Chokshi, Puja D.
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Snippet	Although cytomegalovirus (CMV) infection after allogeneic stem cell transplantation (SCT) is rarely fatal, the management of CMV by pre-emptive medication for... Abstract Background aims Although cytomegalovirus (CMV) infection after allogeneic stem cell transplantation (SCT) is rarely fatal, the management of CMV by...
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SubjectTerms	Adolescent Adult Advanced Basic Science Aged antiviral cellular therapy Child CMV reactivation Cost of Illness Cytomegalovirus - genetics Cytomegalovirus - pathogenicity Cytomegalovirus Infections - economics Cytomegalovirus Infections - pathology Cytomegalovirus Infections - virology economic cost Female Hematologic Neoplasms - mortality Hematologic Neoplasms - pathology Hematologic Neoplasms - therapy Hematopoietic Stem Cell Transplantation - adverse effects Hematopoietic Stem Cell Transplantation - economics Humans Male Middle Aged Other pre-emptive therapy Risk Factors T-Lymphocytes - immunology T-Lymphocytes - pathology T-Lymphocytes - virology Tissue Donors Transplantation, Homologous - adverse effects Transplantation, Homologous - economics Virus Activation - genetics
Title	The clinical and financial burden of pre-emptive management of cytomegalovirus disease after allogeneic stem cell transplantation—implications for preventative treatment approaches
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