Arsenic Trioxide/IFN- Combination Eradicated ATLL in SCID Mice: A Focus on Morphology
ST Saab, H El Hajj, A Bazarbachi, G Zaatari. American University of Beirut, Beirut, Lebanon
Background: We reproduced a previously described Adult T-cell leukemia/lymphoma (ATLL) mouse model to evaluate systemic involvement, disease progression and survival effects of arsenic trioxide (As), interferon- (IFN) and their combination (As/IFN).
Design: Splenic lymphoma cells were transfered from Tax transgenic mice to SCID mice by IP injection. After inoculation (d0), SCID mice were randomized to receive As, IFN, or As/IFN(d6-30);10 mice per group. Another As/IFN group (N=10) underwent identical treatment protocol. Mice were sacrificed at d21, 26, and 30. Finally, As/IFN in two treatment intervals (d6-30 and 42-54)was tested on ten mice. The spleen, liver, lung, bone marrow and kidney were harvested for gross examination and paraffin embedding for all mice.
Results: ATLL was established with untreated mice showing extensive organ involvement(26d average survival). As and IFN showed significant survival advantages over untreated mice and similar systemic involvement. All died of disease(50 and 45d, respectively).
As/IFN cured 40% of mice. At 6mo sacrifice, organs showed near normal morphology. The drug combination tripled survival in the rest (57d). Survival was further enhanced with two courses of As/IFN (80% still alive at 14 mo) and tripled survival (59d) in those that died of disease; slightly improved from the single treatment interval group.
Despite persistent organ involvement at d21, 26 and 30, splenic weights gradually declined with significant tumor regression at d30, signifying a delayed tumor response to As/IFN.
Conclusions: This in vivo model is useful in the morphological evaluation of tumor behavior under chemotherapy effect. As/IFN significantly increased survival and cured a subset of mice. Addition of a second treatment course further enhanced survival and the proportion of cured mice.
Wednesday, March 11, 2009 9:30 AM
Poster Session V # 183, Wednesday Morning