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

Abstract

Background Although CMV infection after allogeneic stem cell transplantation (SCT) is only rarely fatal, the management of CMV by preemptive 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 preemptive strategies, but have yet to be justified in terms of transplant outcome and cost. Patients and methods We compared outcomes and post-transplant treatment cost in 44 patients who never required preemptive CMV treatment with 90 treated patients undergoing SCT at our institute between 2006–2012. 81 subjects received CD34+ selected myeloablative SCT, 12 umbilical cord blood transplants, and 41 T-replete nonmyeloablative SCT. 119 (89%) patients were at risk for CMV because either the donor or recipient was seropositive. Of these, 90 (75.6%) reactivated CMV at a median of 30 (range 8–105) days post transplant and received antivirals. Results There was no difference in standard transplant risk factors between the two groups. In multivariate modeling, CMV reactivation >250 copies/ml (OR=3, P<0.048), total duration of inpatient IV antiviral therapy (OR = 1.04, P<0.001), type of transplant (T-deplete vs. T-replete) (OR=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 post SCT of $58,000 to $74,000/patient. Discussion 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.

Putting a price tag on novel autologous cellular therapies

“…Our case study thus demonstrates that immunotherapy may offer not only significant clinical advantages to immunocompromised patients, but can also be manufactured at a reasonable cost if an appropriate operational model is adopted. Our findings also mirror results from other studies examining the need to reduce the economic burden of post-transplantation care (9,30).…”

“…Thus, adoptive immunotherapies associated with lower toxicities for the prevention and treatment of CMV infection and disease are highly needed and may also produce overall cost savings in posttransplant patient care. Indeed, a recent study has suggested that even if the prevention capabilities of antiviral donor-derived cytotoxic T lymphocytes (CTL) in HSCT, which cost $10,000 to manufacture, would only be 50% effective at avoiding the need for antiviral treatment, it is still considered the less expensive option compared to the cost of antiviral treatment and associated hospital care of more than $50,000 per patient (9). Researchers working in this field anticipate that such therapies could replace conventional treatments, possibly allowing this novel therapeutic category to be accepted as standard practice (10).…”

Impact of early CMV reactivation in cord blood stem cell recipients in the current era

“…Adoptive cellular immunotherapy, after having amassed an excellent record for efficacy and safety, is advancing from therapy of refractory disease to prophylaxis. Boosting immune reconstitution and antiviral immunity post (CB) HCT rather than focusing on pharmacotherapy has the potential to be cost effective 33–35 . Regardless of the approach, our data confirms that there is a great scope for further improving the management of CMV after cord blood HCT.…”

New advances in the management of cytomegalovirus in allogeneic haemopoietic stem cell transplantation

“…The management of CMV viraemia is further complicated by potential treatment toxicities (e.g. ganciclovir‐induced neutropenia, nephrotoxicity), prolonged hospitalisation, worse ICU outcomes, increased risk for other bacterial or fungal infections, increased healthcare costs and contribution to transplant‐related mortality . Overall, it is estimated that the attributable healthcare cost of managing CMV is US$58 000–74 000 per patient, placing a large economic burden on over stretched healthcare resources …”