Baseline levels of innate and adaptive immune cell functions were studied in patients with pancreatic cancer. The effects of pemetrexed were measured at 7 and 14 days after initial therapy then 14 days after combination therapy with gemcitabine. Pretherapy levels of absolute numbers of natural killer (NK) cells positively correlated with survival. Cytolytic units of NK activity correlated positively with NK cell numbers. Pemetrexed decreased NK cytolytic units to significance when combined with gemcitabine. Pemetrexed increased intracellular accumulation of interferon gamma (IFNγ) in NK cells that correlated negatively with survival. Addition of gemcitabine decreased IFNγ-producing NK cells to baseline. Memory (CD45RO*) T cells enumerated at baseline correlated negatively with survival but were decreased by pemetrexed therapy. Memory T cells were increased in subjects with greater B7-H3 expression in tumor tissue, whereas OX40*-activated total T cells and helper T-cell subset were decreased. FoxP3*, CD8* T cells correlated positively with progression-free interval and survival. In conclusion, innate NK-cell immunity and FoxP3*, CD8* T cells seemed beneficial to pancreatic cancer patients. Higher levels of B7-H3 expression in pancreatic tumors were detrimental to effective immunity. Although pemetrexed therapy increased activation of a subset of NK cells to produce IFNγ, addition of gemcitabine abated those responses, decreasing IFNγ-producing NK cells, whereas NK cells producing interleukin-2 without IFNγ at this timepoint positively correlated with survival. Innate immunity and adaptive immunity thus are important in defense against pancreatic cancer. Progression-free interval and survival were longer than observed in a phase III trial where gemcitabine preceded pemetrexed suggesting that a larger trial of pemetrexed preceding gemcitabine is warranted.

Conventional treatment of mantle cell lymphoma (MCL) yields modest responses and short remissions. We report 30 hematopoietic stem cell transplants (HSCT) for MCL: 13 autologous, 10 allogeneic myeloablative, and 7 nonablative. After a median 1.2 years from diagnosis (range 0.5 to 4.7) and a median of 2 pre-HSCT chemotherapeutic regimens (range 1 to 5), their median age at HSCT was 52 years (range 37 to 67). Eleven patients (41%) were in first remission, 11 (41%) were in second remission, and 7 (25%) had resistant disease. Four died early. Nineteen achieved CR (83%) and 4 PR (17%). With median 2.7 years of follow-up, 5-year overall survival (OS) was 42% (95% CI 11-73%) after autologous versus allogeneic at 49% (95% CI 22-76%). Five-year progression-free survival (PFS) was 31% (95% CI 3-59%) and 50% (95% CI 24-76%) for autologous and allogeneic HSCT, respectively. Fourteen died: 3 from sepsis, 1 acute GVHD, 10 MCL. No autologous transplant-related deaths occurred. Allogeneic transplant-related mortality was 29% (95% CI 6-52%) at 1 and 5 years.

Our study indicates that a major disparity in the use of standard therapy for rectal cancer in the older adult exists in academic hospital settings. It will be important for oncologists to reconsider increasing the usage of curative therapy in these patients.

14504 Background: Neoadjuvant or Adjuvant Chemoradiotherapy (CRT) plus surgery is the standard of care for treatment of Stage II/Stage III rectal cancer. Previous studies of practice patterns have evaluated SEER data using single dose chemotherapy as a surrogate for having ever been treated. No study to date has evaluated the use of CRT along with surgery to determine the ability of elderly patients with rectal cancer to complete prescribed therapy. Methods: A retrospective study of all patients treated for Stage II/III rectal cancer identified by Tumor Registrar from January 1, 1987 to June 1, 2006 at the Boston VAMC and Boston Medical Center were analyzed. Data was extracted from computerized records and paper charts. Statistical analysis was performed with SAS software. The primary endpoint was to determine if younger (<70 yr) and older (>=70yr) patients were equally likely to complete CRT and surgery without having a dose of chemotherapy or radiation reduced, held, or delayed. Secondary endpoints were to determine if older and younger age groups were equally likely to receive CRT and a multivariate analysis of factors (age, having received neoadjuvant therapy, number of comorbidities, stage of tumor) had an effect on these outcomes. Results: A total of 266 patients were identified and included in the study. The likelihood of completing CRT and surgery without a dose being held, delayed or reduced was statistically similar among patients age 70 and older (16.1%) as among younger patients (23.9%) (Chi-square 2.16 p=0.1414). However, older patients were far less likely (58.24%) than younger patients (76%) to receive CRT (Chi-square 8.79 p=0.003). A multivariate analysis of factors associated with completion of CRT without a dose being held, delayed or reduced identified only the number of comorbidities (one or more) OR=0.383 (95% CI 0.186–0.790) as statistically significant. In addition, multivariate analysis of factors associated with receiving CRT identified having received neoadjuvant therapy OR=5.397 (95% CI 2.303–12.60) and age >=70 OR=0.424 ( 95% CI 0.201–0.898) as statistically signficant. Conclusion: Elderly patients with rectal cancer are less likely to be prescribed CRT than younger patients. However, elderly patients who are prescribed to receive CRT appear to be able to tolerate the therapy as well as younger patients. No significant financial relationships to disclose.