In chronic lymphocytic leukemia (CLL), the detection of minimal residual disease (MRD) correlates with outcome in the trial setting. However, MRD assessment does not guide routine clinical management and its assessment remains complex. We incorporated detection of the B cell, tumor-specific antigen CD160 to develop a single-tube, flow cytometry assay (CD160FCA) for CLL MRD to a threshold of 10−4 to 10−5. One hundred and eighty-seven patients treated for CLL were enrolled. Utilizing the CD160FCA methodology, there was a high level of comparison between blood and bone marrow (R=0.87, P<0.001). In a validation cohort, CD160FCA and the international standardised approach of the European Research Initiative on CLL group demonstrated high concordance (R=0.91, P<0.01). Patients in complete remission (CR) and CD160FCA negative had longer event-free survival (EFS) (63 vs 16 months, P<0.01) and prolonged time to next treatment (60 vs 15 months, P<0.001) vs MRD positive patients; with a median time to MRD positivity of 36 months. In multivariate analysis, CD160FCA MRD detection was independently predictive of EFS in patients in CR and even predicted EFS in the good-risk cytogenetic subgroup. CD160FCA offers a simple assay for MRD detection in CLL and gives prognostic information across different CLL risk groups.

3063 Background: Depsipeptide, a unique bicyclic peptide histone deacetylase inhibitor (HDACi), has shown activity in a range of in vitro and in vivo tumor models and clinical activity in T-cell lymphomas and prostate cancer. This study seeks to confirm the CTCL activity previously reported by the NCI (Piekarz, et al., ASCO, 2004). Methods: Single-arm, open label study, in 25 centers in the UK, Germany, Poland and the US. Patients aged ≥18 years with biopsy-confirmed CTCL (centrally reviewed) who have failed at least one prior systemic treatment receive up to 6 cycles of depsipeptide as a 4-hour IV infusion on Days 1, 8 and 15 q 28 days. Eligibility criteria include: mycosis fungoides and Sézary syndrome plus variants, Stages IB - IVA, adequate organ function, ECOG PS ≤ 1. Patients with significant cardiovascular abnormalities are excluded in addition to those taking QTc-prolonging or CYP3A4-inhibiting drugs. The primary endpoint is overall reponse rate measured by a combination of imaging, circulating cell counts and a weighted skin average instrument, confirmed by standardized photography. A subset undergoes pharmacokinetic assessments. Correlative studies include acetylation status, apoptotic markers and proteomic analyses where possible. Target accrual is 76 to yield 64 evaluable patients. Results: 30 patients have received treatment with 17 evaluable for efficacy. Responses seen are 1 cCR, 4 PRs (duration 2+ to 6 months) 9 SD and 3 PD. 3 patients withdrew early for PD and 2 for other reasons. The remaining patients on study are too early to assess. Most frequent toxicities are: nausea/vomiting, fatigue, myelosuppression and asymptomatic ECG changes. No patient has withdrawn for toxicity and there have been no treatment-related deaths. Conclusions: The previously reported efficacy of depsipeptide in CTCL has also been seen in the present study. Duration of response is encouraging. Toxicity is manageable and the study continues to accrue. [Table: see text]

The gastrointestinal tract is the commonest extra-nodal site of involvement in B-cell lymphomas and poses particular diagnostic and management problems, including therapy induced bowel perforation and bleeding. Rituximab therapy has demonstrated a significant increase in the complete response rate and prolongs disease free (DFS) and overall survival (OS) in diffuse large B-cell lymphoma. The extra efficacy of rituximab based therapies might increase the immediate complications peculiar to lymphomas of the gastrointestinal tract, particularly perforation. This has not been studied previously. We have reviewed treatment related complications and outcome in 40 cases of primary gastric and intestinal B-cell lymphoma (36 Diffuse Large B-Cell lymphoma, 3 Burkitt Lymphoma, 1 post transplant lymphoproliferative disorder) of the gastrointestinal tract (esophagus 1 case, stomach 21, small bowel 14, ileocaecal 3, large bowel 7;some patients had more than one site involved) over a 25 year period. Rituximab therapy was added to conventional therapy for patients treated in the last 5 years. There were 10 patients (median age 60; range 35–79; M: F=1.5:1) treated with regimens that included rituximab and 30 patients (median age 56; range 12–91; M: F=1.5:1) treated without rituximab. This included chemotherapy (12 patients), surgery alone (2 patients), both surgery and chemotherapy (14 patients) and radiotherapy (1 patient). One patient was not fit for any type of therapy. Complications occurred in 7 patients not treated with rituximab and in 1 patient who received this treatment. Complications included perforation (3 patients treated without rituximab; 1 patient in the rituximab group), bleeding (3 patients treated without rituximab; no episodes of bleeding in the rituximab group) and intestinal obstruction (3 patients in the group not treated with rituximab; no episodes of obstruction in the rituximab treated group). The difference in the complication rate between the two groups was not significant. Five patients in the group that did not receive rituximab died; two of neutropenic sepsis, two of gastric perforation and the other of operative complications. There were no treatment related deaths in the rituximab group. There was one patient in the rituximab treated group and three patients in the group that did not receive rituximab who had refractory disease. The median DFS was 21 and 14 months in patients treated with and without rituximab, respectively (p=0.6). The mean OS was 35 months in the rituximab treated group and 45 months in the group that did not receive rituximab (p = 0.9). There is presently no evidence that rituximab should be withheld early in the treatment of primary gastro-intestinal B-cell lymphomas because of concern about increasing the complication rate.