Viral infections in immunosuppressed patients with hematological malignancies

Abstract

Acute or reactivated viral infections are common in patients who are immunosuppressed because of hematopoietic stem cell transplantation (HSCT) or chemotherapy due to hematological malignancies. The severity of the immunosuppression, the type of immune functions that are affected by various therapeutic interventions, as well as underlying hematological malignancy contributes to viral susceptibility and clinical outcome of the infection. Furthermore, in patients undergoing HSCT, the serostatus of viruses with reactivation capacity in both the recipient and the donor must be considered, as well as the sociodemographic and genetic characteristics.

Here we have studied DNA viruses that can cause clinical events in patients with malignant hematological diseases. Foremost, we evaluated whether it is advisable to continuously screen for the presence of these viruses during illness or chemotherapy in children and adults. In papers I and II we studied the presence of human adenovirus (HAdV) in the blood of patients undergoing HSCT. In papers III and IV, the presence of parvovirus B19 (B19V) in the bone marrow of children with various malignancies was studied, while paper V focused on the presence of B19V in the blood of adults and children undergoing HSCT. Paper VI focused on human herpesvirus 6 (HHV-6), polyoma BK virus (BKV) and B19V in the blood of adult patients undergoing chemotherapy for non-transplanted hematological malignancies. In these retrospective studies, blood and/or bone marrow samples were analyzed by quantitative real-time PCR for DNA representing HAdV, B19V, HHV-6 and BKV. Clinical and laboratory data were obtained from medical records. The proportion of patients with HAdV infection was relatively small, and asymptomatic infections did not occur. On the other hand, HAdV DNA loads >15,000 copies/mL in blood were associated with morbidity and mortality. Furthermore, findings of B19V in bone marrow of children undergoing treatment for acute lymphoblastic leukemia (ALL), were associated with prolonged chemotherapy. Neither B19V, HHV-6A, 6B nor BKV was common in the blood of adult patients with hematological malignancies who were immunosuppressed due to chemotherapy.

In general, screening for these viruses in the patient groups presented may not be indicated at the current state. However, testing for HAdV should be performed generously when unexpected symptoms occur, even if they are not typical for the virus. B19V infection is almost always linked with some degree of cytopenia, and if unexpected cytopenia occurs in children undergoing chemotherapy, B19V infection should be tested for. Patients with primary infections normally suffer from more severe clinical disease as compared to those with reactivated infections. Thus, knowledge of viral serostatus in HSCT recipients and donors should be taken into account in diagnostic considerations.

Overall, the diagnostic value of direct viral detection in blood and/or bone marrow samples of immunosuppressed patients with hematological malignancies is of considerable importance. Hopefully, a broad spectrum of novel antiviral compounds as well as novel procedures for adoptive cell therapy will be developed for these viral infections. Whether novel interventions will be used as pre-emptive therapy, or as symptomatic treatment, there will be an urgent need to monitor viral load. The present thesis can thus inform the field of clinically relevant viral infections and how to monitor these in selected patient categories that can be targeted for future therapeutic clinical interventions.