Publication: Therapeutic trials for a rabbit model of
EBV-associated Hemophagocytic Syndrome (HPS):
Effects of vidarabine or CHOP, and development of
Herpesvirus papio (HVP)-negative lymphomas
surrounded by HVP-infected lymphoproliferative disease
Authors
Hayashi, K. ; Joko, H. ; Koirala, T.R. ; Onoda, S. ; Jin, Z.S. ; Munemasa, M. ; Ohara, N. ; Oda, W. ; Tanaka, T. ; Oka, T. ; Kondo, E. ; Yoshino, T. ; Takahashi, K. ; Yamada, M. ; Akagi, T.
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Publisher
Murcia : F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
Abstract
Epstein-Barr virus-associated hemophagocytic
syndrome (EBV-AHS), which is often associated
with fatal infectious mononucleosis or T-cell
lymphoproliferative diseases (LPD), is a distinct disease
characterized by high mortality. Treatment of patients
with EBV-AHS has proved challenging. To develop
some therapeutic interventions for EBV-AHS, we
examined the effectiveness of an antiviral agent
(vidarabine) or chemotherapy (CHOP), using a rabbit
model for EBV-AHS.
Fourteen untreated rabbits were inoculated
intravenously with cell-free virions of the EBV-like virus
Herpesvirus papio (HVP). All of the rabbits died of
HVP-associated (LPD) and hemophagocytic syndrome
(HPS) between 21 and 31 days after inoculation.
Furthermore, three HVP-infected rabbits treated with
vidarabine died between days 23 and 28 after
inoculation, and their clinicopathological features were
no different from those of untreated rabbits, indicating
that this drug is not effective at all to treat HVP-induced
rabbit LPD and HPS.
Three of the infected rabbits that were treated with
one course, with an incomplete set of three courses, or
with three full courses of CHOP treatment died of HVPinduced
LPD and HPS with a bleeding tendency and/or
with opportunistic infections. They died on the 26th,
62nd and 105th day after virus inoculation, respectively.
CHOP treatment transiently suppressed the HVPinduced
LPD and contributed to the prolonged survival
time of two infected rabbits. However, it did not remove
all of the HVP-infected cells from the infected rabbits,
and residual HVP-infected lymphocytes caused
recurrences of rabbit LPD and HPS. The most interesting finding of this experiment was observed in
the infected rabbit with the longest survival time of 105
days: HVP-negative lymphomas surrounded by HVPinduced
LPD developed in the larynx and ileum of this
rabbit, causing an obstruction of the lumen. We
concluded that these were not secondary lymphomas
caused by CHOP treatment, because no suspicious
lesions were detected in three uninfected rabbits that
were treated with three courses of CHOP for 120 days. It
is therefore necessary to clarify the mechanism by which
HVP-negative lymphomas associated with HVP-induced
LPD can develop.
Our data from therapeutic trials using EBV-AHS
animal models indicate that vidarabine is not effective as
an agent to treat HVP-infected rabbits, and even the
cytotoxic chemotherapy of CHOP is not sufficient to
cure the HVP-infected rabbits or to prolong the survival
time of infected rabbits. Further studies will therefore be
required to develop better therapies to treat EBV-AHS.
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