Cytotoxic drug sensitivity of Epstein-Barr virus transformed lymphoblastoid B-cells.
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.


CONCLUSIONS
Our data shows that the inclusion of epirubicin and paclitaxel into chemotherapy protocols against PTLD may be justified.
Markasz
Laszlo
L
Department of Microbiology, Tumor and Cell Biology and Center for Integrative Recognition in the Immune System, Karolinska Institute, Box 280 S-17177 Stockholm, Sweden. markaszl@freemail.hu <markaszl@freemail.hu>
Stuber
György
G
Flaberg
Emilie
E
Jernberg
Asa Gustafsson
AG
Eksborg
Staffan
S
Olah
Eva
E
Skribek
Henriette
H
Szekely
Laszlo
L
D000970:Antineoplastic Agents / Q000633:toxicity*; D000998:Antiviral Agents / Q000494:pharmacology*; D001402:B-Lymphocytes / Q000187:drug effects / Q000821:virology*; D016026:Bone Marrow Transplantation / Q000009:adverse effects; D045744:Cell Line, Tumor; D002472:Cell Transformation, Viral; D004854:Herpesvirus 4, Human / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008223:Lymphoma / Q000188:drug therapy*; D008232:Lymphoproliferative Disorders / Q000188:drug therapy* / Q000276:immunology; D011183:Postoperative Complications / Q000276:immunology
D000970:Antineoplastic Agents; D000998:Antiviral Agents