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An ever-looming threat: infections in immunocompromised hosts

Burden of Viral Infections among Autologous Stem Cell Transplant Patients: A Prospective Longitudinal Study

April 19 • O0363

G. Destras1/2, A. Bal1/2/3, P. Sesques4, C. Sarkozy4, L. Generenaz3, G. Oriol3, G. Salles4, B. Lina1/2, F. Mallet3, A. Pachot3, G. Billaud1, L. Josset1/2, S. Trouillet-Assant2/3, V. Cheynet3, K. Brengel-Pesce3, F. Morfin1/2

1) Laboratoire de Virologie, Institut des Agents Infectieux, Groupement Hospitalier Nord, Hospices Civils de Lyon, Lyon, France
2) Univ Lyon, Université Lyon 1, CIRI, Inserm U1111 CNRS UMR5308, Virpath, Lyon, France
3) Joint research unit Hospices Civils de Lyon - bioMérieux, Centre Hospitalier Lyon Sud, 165 Chemin du Grand Revoyet, 69310 Pierre-Bénite, France
4) Service d'hématologie clinique, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Pierre-Bénite, France

Background: Hematopoietic stem cell transplantation remains the only curative treatment for many hematological disorders. Surrounding this immunosuppressive therapy, viral reactivations caused by herpesviruses, adenovirus, BK virus require particular attention to prevent organ damage. Despite some severe cases reported in autologous stem cell transplant (ASCT) patients, few recommendations regarding the management of viral infections have been established so far. We aimed to investigate viral infections in patients who underwent ASCT in a large prospective longitudinal study.

Material and Methods: A systematic screening of plasma viral load, targeting 9 viruses at 11 time-points (from diagnosis to 90 days post transplantation), was performed on 477 samples from 48 patients (n=42 multiple myeloma, n=6 lymphoma) prospectively enrolled. Clinical criteria and hemogram values were collected. All patients received antiviral prophylaxis with valaciclovir.

Results: Of 4293 PCRs performed, 86 (2.0%) were positive corresponding to 75/477 (15.7%) samples. While sixteen patients (35%) had no virus detected during follow-up, most positive samples (56%) were found after aplasia and 30 days after transplantation. Patients mainly presented CMV reactivation (59% of CMV seropositive patients). Overall, low viral loads (<3 log copies/mL) were found except for one patient with parvovirus B19 primary infection (11.85 log copies/ml), and for two patients with HHV6 (3.84 log copies/ml) and CMV (4.50 log copies/ml) clinical reactivations. For this latter patient, CMV was also the unique pathogen identified in the bronchoalveolar lavage collected during an interstitial pneumonia episode requiring 6 days of hospitalization. No specific reactivation was associated with clinical or biological criteria. Interestingly, no reactivation was found in multiple myeloma patients treated with daratumumab, a cd-38 monoclonal antibody for which an increase in viral reactivations was previously reported.

Conclusion: This is the largest prospective study reported so far describing viral detection during the follow-up of ASCT patients. We found a limited clinical impact of viral reactivations in these patients treated with valaciclovir, suggesting a potential benefit of administering an antiviral prophylaxis in all ASCT patients (not yet recommended). However, CMV testing should be systematically considered in case of infectious complications. This study might contribute to upgrade guidelines regarding ASCT patient management.

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Molecular

2-Hour Oral session