BLOG: Update on double-stranded DNA viruses from Tandem Meetings
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Reactivation of double-stranded DNA viruses is an important cause of morbidity and mortality after hematopoietic stem cell transplantation.
We highlight studies on the biology, risk factors and management of viral reactivations.
Regimens for graft-versus-host disease prevention potentially may increase infection risk.
The FDA approved abatacept (Orencia, Bristol Myers Squibb) for acute GVHD prevention based in part on results of the ABA2 trial.
The trial did not show a signal for increased cytomegalovirus or Epstein-Barr virus with abatacept.
Albanese and colleagues studied the immune reconstitution of placebo and abatacept-treated patients who received 8/8 HLA-matched HCT. They demonstrated equivalent T-cell repertoire reconstitution as measured by T-cell receptor sequence clonality.
Their results further substantiate intact T-cell reconstitution with abatacept.
Letermovir prophylaxis has reduced clinically significant cytomegalovirus infections (CS-CMVi) in the first 100 days among cytomegalovirus-seropositive (R+) HCT recipients.
Rebound (CS-CMVi), however, may occur in the setting of delayed immune reconstitution.
Dadwal and colleagues presented the results of a randomized phase 3, placebo-controlled clinical trial that evaluated the safety and efficacy of extending letermovir prophylaxis from day 100 to day 200 among R+ HCT recipients.
The trial met its primary endpoint — proportion of patients with CS-CMVi between week 14 and week 28 after HSCT — with significantly lower CS-CMVi in letermovir group vs. placebo group (95% CI, -25.8 to -6.5), with a P value of 0.0005. Letermovir extension to day 200 after HSCT was safe and well tolerated.
Rosa and colleagues studied vaccination of cytomegalovirus R+ stem cell donors as an alternative approach to pharmacologic cytomegalovirus prevention.
In a pilot study, R+ patients received an HCT from cytomegalovirus-seropositive matched-related donors vaccinated once with Triplex (Helocyte Inc.), a recombinant modified vaccinia Ankara (MVA) viral vector expressing immunodominant cytomegalovirus antigens, a median 15 days prior to stem cell harvest.
On day 28 after HCT, levels of functionally activated cytomegalovirus-specific CD8+ T cells were significantly higher among Triplex-vaccinated HCT donors compared with HCT recipients from unvaccinated donors. Predominantly central and effector memory cytomegalovirus-specific T-cell responses continued to expand in the donor-vaccinated recipients through 1-year follow up.
Thrombotic microangiopathy is the final common pathway of endothelial injury.
Thrombotic microangiopathy occurs in 20% to 30% of pediatric HCT.
Sabulski and colleagues explored the mechanisms of BK polyomavirus (BKPyV) cystitis in two pediatric cohorts.
Proteomic analyses showed signaling pathway overlap between BKPyV cystitis and thrombotic microangiopathy, suggesting that thrombotic microangiopathy may contribute to cystitis.
Further studies are needed to better define this relationship and guide development of targeted therapies.
Off-the-shelf, third-party, multivirus specific T cells are in phase 3 trials for prevention of viral reactivations in high-risk patients.
Yared and colleagues presented the outcomes of a phase 2, open-label trial of posoleucel (Viralym-M, AlloVir) for prevention of clinically significant infection or end-organ disease from cytomegalovirus, Epstein-Barr virus, human herpesvirus 6, BK virus, JC virus and adenovirus.
Patients received posoleucel starting at a median 43 days, for seven planned doses over 14 weeks.
Posoleucel was well tolerated. Researchers noted no signal of increased GVHD, with low rates of clinically significant infections/early-onset disease, and viral control was associated with expansion of reactive T cells.
References:
The following were presented at Tandem Meetings | Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR, Feb. 15-19, 2023; Orlando:
- Albanese A, et al. Abstract 334.
- Dadwal SS, et al. Abstract 76.
- Dadwal SS, et al. Abstract 78.
- La Rosa C, et al. Abstract 82.
- Sabulski A, et al. Abstract 77.
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