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Background: Paraneoplastic pemphigus (PNP) is an autoimmune mucocutaneous disease associated with cancer. Since the original description of the condition, various publications have suggested the presence of a heterogeneous spectrum of paraneoplastic mucocutaneous conditions with clinical features of lichenplanus. Several cases of PNP have been reported following treatment with fludarabine. Methods: We present a case of lichenoid syndrome in a follicular B-cell non-Hodgkin lymphoma (NHL) patient after treatment with fludarabine and review 8 additional published cases of fludarabine related PNP. Results: Our case is unique due to the fact that the patient presented with lichenoid features both clinically and microscopically and responded well to rituximab therapy. According to literature, both skin and mucosa (eyes and gastrointestinal tract) are involved and symptoms start about 1-2 weeks after exposure to fludarabine. Various immunosuppressive treatments have been employed including high dose steroids. Many of these patients developed complications related to the immunosuppressive therapy such as cytomegalovirus, candidiasis and pneumocystis carinii infection and died from respiratory failure. On the other hand, long-term remissions have also been described. Conclusion: Our case represents an unusual case of fludarabine related to mucocutaneous lichenoid syndrome, a variant of PNP, and in view of the outcome in previously described cases, rituximab may be considered a preferred and safe first line therapy for such complication.

Follicular small cell and follicular mixed small and large cell lymphoma (FL) are incurable with conventional chemotherapy, and generally follow a relapsing course, eventually becoming resistant to first-line therapy with alkylating agents. Fludarabine is a novel chemotherapeutic agent that is effective in FL, but its role in alkylator-resistant disease remains unclear. We conducted a retrospective review of all patients with alkylator-resistant FL treated with fludarabine. Patients were identified from pharmacy records and included if they fulfilled criteria for alkylator-resistant FL. Resistance was defined as failure to achieve a partial response, progression while on therapy, or relapse within six months of completing therapy. Seventeen patients met the criteria of alkylator-resistant FL and were included in the analysis. All patients received fludarabine 25 mg/m(2) for five days. A median of 2.5 courses of fludarabine was given. One patient had a complete remission and eight patients had partial remissions, for an overall response rate of 53%. Median progression-free survival was 5.4 months and median overall survival was 15.4 months for all patients. Four patients underwent subsequent autologous stem cell transplantation; all required additional salvage chemotherapy for post-fludarabine relapses. Three patients remain in remission more than 12 months post-transplantation. Fludarabine produces partial responses in patients with advanced refractory FL; however, the duration of the response limits its utility in alkylator-resistant disease.

In an attempt to further define prognostic factors in patients with follicular non-Hodgkin's lymphoma, two subgroups of patients receiving 2nd line therapy; (a) those who had failed to achieve CR with initial therapy and (b) those who had relapsed after achieving initial CR, were examined. Patients who failed to achieve initial remission were not totally refractory to retreatment. Seven of 34 (21%) who had failed to respond to initial treatment achieved CR following treatment with various 'salvage chemotherapy' approaches. There were, however, no significant pretreatment prognostic factors that were predictive for response. Among patients who relapsed after initial CR, 22 of 54 (41%) achieved a second CR following retreatment with conventional chemotherapy approaches. The only factors which were significant in predicting for second CR were sex (female) and age (60 years). In both subgroups, patients who achieved CR following 'salvage' therapy survived significantly longer than those who responded less favourably. These findings emphasise the fact that response to treatment is the major predictor of survival among patients with indolent non-Hodgkin's lymphomas.

PURPOSE To evaluate polymerase chain reaction (PCR) analysis as a method for the detection of circulating lymphoma cells in patients with stage III and IV t(14; 18)-positive follicular Non-Hodgkin's lymphoma (NHL) in first remission in a longitudinal prospective study. PATIENTS AND METHODS Peripheral blood or bone marrow from eight patients with stage III and IV t(14; 18)-positive NHL was studied using PCR to detect the presence of t(14; 18)-positive cells in the circulation at different times during first remission. RESULTS In four of six patients with no clinical evidence of disease (NCED), t(14; 18)-positive cells were detectable in the circulation. In one of two patients with clinical evidence of disease (CED), no t(14; 18)-positive cells were found at the four different occasions tested during first remission. First-remission duration ranged from 17 to 81+ months. The duration from the first PCR determination in remission until first relapse or the end of the observation period ranged from 10 to 37+ months. CONCLUSION In patients with t(14; 18)-positive follicular NHL stage III and IV, treated with conventional remission induction therapy, the presence or absence of t(14; 18)-positive cells in the circulation shows no obvious correlation with the clinical remission status and the remission duration.

A case of centroblastic centrocytic follicular lymphoma arising within a bilateral adenolymphoma of the parotid glands with Involvement of the adjacent lymph nodes is reported. The patient was treated with combination chemotherapy and three years after the first cycle of therapy there was no evidence of disease. The occurrence of primary malignant lymphomas in the lymphoid stroma of an adenolymphoma has seldom been discussed in literature. All cases reported of follicular centre cell type were characterized by an indolent clinical course.

The overall survival with follicular lymphoma has not significantly changed over the last few decades, and there is no universal agreement as to the optimal first-line or subsequent therapy. High-dose chemotherapy with autologous hematopoietic cell transplantation (HCT) confers high response rates and improved progression-free survival in advanced-stage disease, and more recent data indicate a positive effect on overall survival. Initial results with myeloablative allogeneic HCT unequivocally demonstrated a reduction in relapse/progression compared with autologous HCT, but it is associated with prohibitive nonrelapse mortality. Nonmyeloablative or reduced-intensity regimens have substantially reduced up-front toxicity, and preliminary data seem highly encouraging with regard to efficacy. Novel strategies include the use of rituximab for in vivo purging and maintenance therapy. The incorporation of radioimmunoconjugates into conditioning regimens to deliver targeted radiotherapy also appears promising. This review summarizes current and new developments regarding the role of HCT for patients with follicular lymphoma.

We report an unusual patient with a 21 year history of lymphoma of three different histological varieties: a low grade follicular non-Hodgkin's lymphoma, mixed cellularity Hodgkin's disease and a high grade B cell monocytoid non-Hodgkin's lymphoma.

Denileukin diftitox (ONTAK ® ) is indicated for the treatment of patients with cutaneous T cell lymphoma. Clinical experience with this drug in other lymphomas is limited. This case report concern a patient with stage IV follicular lymphoma who, relapsing after autologous transplant and having failed multiply systemic therapies, including retuximab and CHOP, achieved a prolonged remission with denileukin diftitox.

Abstract 1522 Background: Follicular NHL (f-NHL) accounts for approximately 70% of indolent lymphomas. We estimated the marginal cost of progression for patients with f-NHL treated in the outpatient community setting. Methods: Using US Oncology's iKnowMed electronic medical records (EMR), we identified 1002 f-NHL patients who achieved complete remission or had documented stable disease between 7/1/2006 and 2/29/2008. This database captures information in a network of about 1,200 community-based oncologists where patients are treated according to usual clinical practice with no criteria for therapy selection and no schedule of visits imposed. To estimate outpatient cost of care, we linked the EMR data to US Oncology's claims data warehouse. Patients were categorized into 2 cohorts based on whether they experienced disease progression or not. Patient demographic and clinical information were characterized at baseline and follow-up time was censored at the last entry for disease status or 6 months after date of complete remission/ stable disease or date of progression. Costs per patient month (estimated based on outpatient claims and normalized to 2007 Medicare reimbursement rates) were compared between progressed and non-progressed patients. Econometric regression analysis was used to compare healthcare cost after adjusting for potential confounders. To further explore the economic burden of progression, we compared resource utilization as measured by outpatient physician visits, chemotherapy visits, laboratory and acute care visits. Results: Of the 1,002 f-NHL patients identified, 204 progressed and 798 did not. At baseline, patients who progressed were more likely to have been diagnosed with advanced disease, have 4+ positive lymph nodes, have worse ECOG performance status and high LDH and low HGB levels compared to patients who did not progress. The mean overall costs per patient-month over the 6-month follow-up period were significantly higher for patients who progressed vs. those who did not progress ($3612 vs. $965; difference = $2,647; p Conclusions: Results of this retrospective study indicate that therapies which delay disease progression for f-NHL may provide substantial economic benefits in addition to improvements in clinical outcomes. Disclosures: Hoang: Genentech: Consultancy. Gruschkus:US Oncology: Employment. Darragh:US Oncology: Employment. Forsyth:US Oncology: Employment. Beveridge:US Oncology: Consultancy, Employment. Reyes:Genentech Inc: Employment.

8065 Background: The F158V variant of the Fc gamma 3A receptor (FCGR3A) correlates with clinical response to rituximab. In SAKK 35/98 (NCT00003280), patients (pts) received rituximab induction ther...

17528 Background: There is no data regarding safety and efficacy of treating follicular NHL patients with a second course of 90Y ibritumomab tiuxetan (Zevalin). Methods: Patients with follicular NHL who received 2 courses of Zevalin therapy were identified nationally, and data was retrospectively collected. Results: 10 patients (pts) (mean age 62.5 years, 48–91) were identified. Prior to the first Zevalin, all pts received chemotherapy (mean 2.4 courses, 1–5), 3/10 auto-PBSCT, and 4/10 external beam radiotherapy(ebRT). After the initial course of treatment, the mean time to nadir for the anemia was 7.9 weeks (wks)(4–13), neutropenia was 6.7 wks (4–10); and thrombocytopenia was 5.2 wks (4–8). 1 pt required growth factor support and transfusions; 2 had an incomplete recovery of platelet count at 23 and 30 wks (76,000 and 126,000/μl). Hematologic toxicity and grades are in the table below. Prior to the second course of Zevalin 2 pts received ebRT, 1 received 131I tositumomab, and 3 received chemotherapy (1–5 regimens). The median time to the second Zevalin course was 613 days (183–1,300). After the second course of Zevalin, the mean time to nadir for the anemia was 8.2 wks (2–25); neutropenia was 6.7 wks (4–10); and thrombocytopenia was 5.5 wks (4–7). 4/10 pts required growth factor support, 2 required transfusions, 3 had incomplete recovery of platelet count and early progression, 2 pts had a maximum recovery of their platelet count at 29 and 40 wks (143,000 and 144,000/μl). There were no infectious or bleeding complications with either course of Zevalin. No secondary myelodysplastic syndrome or acute leukemia were reported. Conclusions: Retreating patients with follicular NHL with a second course of Zevalin is tolerable with substantial evidence of clinical efficacy. This data warrants further evaluation of Zevalin retreatment in a clinical trial. [Table: see text] [Table: see text]

6567 Background: The potential for long term disease-free survival for patients with recurrent follicular lymphoma receiving high-dose chemotherapy and an autologous hematopoietic stem cell transpl...

6520 Background: A phase II, open-label, multicenter study was conducted to determine the efficacy of Bexxar therapy following CVP in pts with previously untreated follicular NHL. Methods: Pts rece...

Purpose/Objective: In a first prospective non randomized trial, 107 patients with stage III and IV “low-grade” lymphomas have been treated with a combination of chemotherapy and low-dose Total Body Irradiation (LD-TBI) [Richaud and Hozrni, 19921. This study show that this scheme of LD-TBI was very well tolerated, gave a high response rate (83%) and extended RFS. It incite us to start a pilot study on localized follicular lymphomas.

75 cases treated between 1970 and 1976 for malignant follicular non-Hodgkin's lymphoma were analysed for their cardinal signs. Contrary to non-Hodgkin's lymphoma of "higher malignancy degree", the average age of patients with malignant follicular non-Hodgkin's lymphoma is generally over 50 years, being more common in females. By the time the diagnosis is made a generalised stage has usually been reached. In the described group of patients the five-year survival rate was 65%, but compared with the malignant lymphoma of higher malignancy the prognosis is often complicated by secondary diseases resulting from the higher age. The findings confirm the need for histological sub-classification of malignant non-Hodgkin's lymphoma.

Summary FL is usually widely disseminated at presentation and responds to radiotherapy, single agent chemotherapy and combination therapy. The disease pursues a remitting and relapsing course with continuing sensitivity to brief periods of treatment until a terminal phase of drug resistance, transformation, or bone marrow failure is reached. Newly recognized prognostic factors indicative of tumour bulk include hepatosplenomegaly, B symptoms, anaemia and abnormal liver function. Using these factors it is possible to identify those patients at first diagnosis for whom conservative management is appropriate and those with a much less favourable prognosis for whom experimental treatments are being investigated.