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

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.

Selectively T cell-depleted allografts from HLA-matched sibling donors followed by low-dose posttransplantation immunosuppression to improve transplantation outcome in patients with hematologic malignancies.

We evaluated a photodepletion technique to selectively deplete host-reacting T cells from human leukocyte antigen (HLA)-matched sibling stem cell transplantations with the goal of reducing posttransplantation immunosuppression to improve antimalignancy effects postallografting. Donor lymphocytes were stimulated with irradiated expanded recipient T lymphocytes in an ex vivo mixed lymphocyte reaction. Alloactivated T cells preferentially retaining the photosensitizer 4,5-dibromorhodamine 123 (TH9402) were eliminated by exposure to visible light. Twenty-four patients with hematologic malignancies (16 high risk) conditioned with fludarabine, cyclophosphamide, and totalbody irradiation received a CD34-selected stem cell allograft from an HLA-matched sibling along with 5 × 10(6)/kg selectively depleted donor T cells. Low-dose cyclosporine was used for posttransplantation immunosuppression. Eleven patients survived at a median of 30 months. Probabilities (± SEM) for overall and disease-free survival are 39% ± 12% and 30% ± 12%, respectively, whereas grade III-IV acute graft-versus-host disease (aGVHD) was 13% ± 7%. Six patients relapsed, with a relapse probability of 27% ± 10%. These results suggest that selectively photodepleted allografts in matched sibling transplantations followed by low-dose immunosuppression may protect against severe aGVHD but is associated with delayed immune recovery.

Radiation exposure from diagnostic procedures following allogeneic stem cell transplantation--how much is acceptable?

BACKGROUND: Frequent diagnostic radiology procedures in allogeneic stem cell transplantation (SCT) recipients raise concern about the potential harm from incidental radiation. OBJECTIVES: To determine the cumulative radiation dose from diagnostic studies in allogeneic SCT and its impact on clinical outcome. PATIENTS AND METHODS: This retrospective cohort study was conducted to determine the cumulative radiation dose from diagnostic studies following SCT. Sixty-four consecutive patients with hematological malignancies in a single tertiary care institution underwent total body irradiation (TBI)-based myeloablative conditioning followed by six of six human leukocyte antigen (HLA)-identical sibling allogeneic SCT. The median follow-up was 3 years. The cumulative effective dose in mSv from diagnostic radiological studies in the peri-transplant period from day -30 to day +200 was calculated for each patient and its impact on overall survival and non-relapse mortality was determined. RESULTS: The median cumulative radiation exposure from diagnostic radiological procedures was 92 mSv (range 1.2-300), representing about 30× the normal annual background radiation for the population and 10% of the 1200 cGy TBI dose used in conditioning. Sixty-five percent of the cumulative radiation exposure was delivered between day +1 and day 100 and computed tomography scans contributed 88%. In multivariate analysis, diagnostic procedures did not significantly impact clinical outcomes. CONCLUSIONS: While radiation exposure from diagnostic procedures did not impact clinical outcomes the risk of secondary cancers in long-term survivors is likely to be increased. Our results indicate that patients who are acutely ill for prolonged periods can receive clinically significant radiation doses during their hospital care. Our findings should prompt attempts to limit radiation exposure from diagnostic procedures in post-SCT recipients.