Treatment and biology of lymphomatoid granulomatosis
8029 Background: LYG is a rare angiocentric-destructive process with EBV+ B-cells and reactive T-cells. LYG is graded with grades I-II showing rare-moderate large EBV+ B-cells (usually polyclonal or oligoclonal) and grade III showing numerous large EBV+ B-cells (usually monoclonal), likely reflecting progressive transformation. Historically, steroids and/or chemotherapy have a 14 mos median survival. Methods: We are investigating Interferon-a (I-a) for grade I/II and dose-adjusted EPOCH ±Rituximab (R) for grade III LYG. Results: Characteristics of 53 pts are: male sex 68%; median age (range) 46 (17–67) and median ECOG P.S. 1 (0–3). Disease sites include lung 98%, CNS 38%, kidney 15%, skin 17%, liver 19% and nodes 4%. On study LYG grades are I-30%, II-26% and III-44%. Prior treatment was none-28%, chemotherapy± R-34%, and steroids alone-40% of pts. For grades I/II, I-a is begun at 7.5 million IUs TIW and escalated as tolerated until disease regression and continued 1 yr after CR. Of 31 patients treated with I-a, PFS is 62% at the median f/u of 5.3 yrs. Of 25 evaluable pts (3 NE; 3 TE), 60% had sustained CR for a median of 60 mos (4–175). In 9 pts who progressed on I-a, grade III was found in 5. Thus, in 20 pts with only grade I/II, 75% had sustained CR with I-a. In 11 evaluable pts with CNS disease, 81% achieved remission with I-a alone. The median time to remission is 9 mos (3–40) and median I-a dose is 20 MIU (7–40). Among 24 pts receiving DA-EPOCH±R, PFS is 40% at the median f/u of 28 mos. Of 21 evaluable pts (2 NE, 1 TE), 66% achieved CR. OS of all 53 pts is 68% at the median f/u of 4 yrs. Median EBV viral loads in 29 pts at study entry were 18 copies/10e6 genome equivalents (0–22727) (normal<200). Lymphocyte subsets in 30 pts showed a median CD4–428 (24–2322) and CD8–165 cells/mm3 (42–1316). In 12 pts in CR and with serial values, the mean CD8 cells (131 ± 44) (p2= 0.013) but not CD4 cells (65 ± 75) increased with treatment. Conclusions: High dose I-a produces sustained remissions in grade I/II LYG and is effective in CNS LYG. DA-EPOCH±R can produce durable CRs in grade III LYG. We hypothesize LYG emerges in a compromised immune milieu and undergoes progressive transformation if not effectively treated. Historical results suggest steroids may allow transformation by compromising immune function. No significant financial relationships to disclose.