BACKGROUND: Epstein-Barr virus (EBV) is the causative agent of immunosuppression
associated lymphoproliferations such as post-transplant lymphoproliferative
disorder (PTLD), AIDS related immunoblastic lymphomas (ARL) and immunoblastic
lymphomas in X-linked lymphoproliferative syndrome (XLP). The reported overall
mortality for PTLD often exceeds 50%. Reducing the immunosuppression in
recipients of solid organ transplants (SOT) or using highly active antiretroviral
therapy in AIDS patients leads to complete remission in 23-50% of the PTLD/ARL
cases but will not suffice for recipients of bone marrow grafts. An additional
therapeutic alternative is the treatment with anti-CD20 antibodies (Rituximab) or
EBV-specific cytotoxic T-cells. Chemotherapy is used for the non-responding cases
only as the second or third line of treatment. The most frequently used
chemotherapy regimens originate from the non-Hodgkin lymphoma protocols and there
are no cytotoxic drugs that have been specifically selected against EBV induced
lymphoproliferative disorders. METHODS: As lymphoblastoid cell lines (LCLs) are
well established in vitro models for PTLD, we have assessed 17 LCLs for cytotoxic
drug sensitivity. After three days of incubation, live and dead cells were
differentially stained using fluorescent dyes. The precise numbers of live and
dead cells were determined using a custom designed automated laser confocal
fluorescent microscope. RESULTS: Independently of their origin, LCLs showed very
similar drug sensitivity patterns against 29 frequently used cytostatic drugs.
LCLs were highly sensitive for vincristine, methotrexate, epirubicin and
paclitaxel. CONCLUSION: Our data shows that the inclusion of epirubicin and
paclitaxel into chemotherapy protocols against PTLD may be justified