Faculty Bibliography

PURPOSE: To determine the clinical and biologic effects of bevacizumab, an anti-vascular endothelial growth factor (VEGF) monoclonal antibody, in unresectable hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Adults with organ-confined HCC, Eastern Cooperative Oncology Group performance status of 0 to 2, and compensated liver disease were eligible. Patients received bevacizumab 5 mg/kg (n = 12) or 10 mg/kg (n = 34) every 2 weeks until disease progression or treatment-limiting toxicity. The primary objective was to determine whether bevacizumab improved the 6-month progression-free survival (PFS) rate from 40% to 60%. Secondary end points included determining the effects of bevacizumab on arterial enhancement and on plasma cytokine levels and the capacity of patients' plasma to support angiogenesis via an in vitro assay. RESULTS: The study included 46 patients, of whom six had objective responses (13%; 95% CI, 3% to 23%), and 65% were progression free at 6 months. Median PFS time was 6.9 months (95% CI, 6.5 to 9.1 months); overall survival rate was 53% at 1 year, 28% at 2 years, and 23% at 3 years. Grade 3 to 4 adverse events included hypertension (15%) and thrombosis (6%, including 4% with arterial thrombosis). Grade 3 or higher hemorrhage occurred in 11% of patients, including one fatal variceal bleed. Bevacizumab was associated with significant reductions in tumor enhancement by dynamic contrast-enhanced magnetic resonance imaging and reductions in circulating VEGF-A and stromal-derived factor-1 levels. Functional angiogenic activity was associated with VEGF-A levels in patient plasma. CONCLUSION: We observed significant clinical and biologic activity for bevacizumab in nonmetastatic HCC and achieved the primary study end point. Serious bleeding complications occurred in 11% of patients. Further evaluation is warranted in carefully selected patients

Recently, donation after cardiac death (DCD) has been encouraged in order to expand the donor pool. We present a case of anaplastic T-cell lymphoma transmitted to four recipients of solid organ transplants from a DCD donor suspected of having bacterial meningitis. On brain biopsy, the donor was found to have anaplastic central nervous system T-cell lymphoma, and the recipient of the donor's pancreas, liver and kidneys were found to have involvement of T-cell lymphoma. The transplanted kidneys and pancreas were excised from the respective recipients, and the kidney and pancreas recipients responded well to chemotherapy. The liver recipient underwent three cycles of chemotherapy, but later died due to complications of severe tumor burden. We recommend transplanting organs from donors with suspected bacterial meningitis only after identification of the infectious organism. In cases of lymphoma transmission, excision of the graft may be the only chance at long-term survival

Introduction: Quantifying cellularity is an integral component of bone marrow examinations. Estimates of marrow cellularity may influence the diagnostic interpretation of bone marrow samples. The accuracy of cellularity estimates may be influenced by the variable distribution of cellular elements within the marrow space. To better understand the degree of heterogeneity of bone marrow cellularity, we undertook a study to quantify the variable distribution of bone marrow cells in bone marrow core biopsies. Method: 8 gauge bone marrow core biopsies of 20 patients were retrospectively reviewed by 2 hematopathologists (SI,CL). The specimens were recovered from the posterior superior iliac crest using standard technique with 8G Snarecoil biopsy needles by 3 operators (KH, PK, GD). The percent cellularity was determined in sequential 0.2 X 0.4 cm portions of the core biopsies by each of the hematopathologists. Cellularities were recorded in 10% increments. Results: The mean age of the patients was 73.2 1.8 years. There were 12 males and 8 females. 5 patients had monoclonal gammopathies. Anemia, multiple myeloma and thrombocytopenia were each diagnosed in three patients. 2 patients demonstrated myelodysplasia and 1 patient each had acute leukemia, leukocytosis, non-Hodgkin's lymphoma and thrombocytosis. The mean white blood cell count, hemoglobin and platelet count were 8.7 (range 3.842.8), 12.2 (range 10.115.3), and 233 (range 91226), respectively. The mean length of the core biopsies was 1.78 0.09 cm (range 1.43.3) and the median number of 0.2 x 0.4 cm portions examined per core biopsy was 8 (range 512). In total, 165 portions were examined by each hematopathologist independently. The cellularity of 12 and 11 portions could not be determined by each of the hematopathologists, respectively, as a result of biopsy artifacts. No core biopsy showed a consistent cellularity within the examined portions, each core demonstrating a range of cellularities. Only 2/20 and 1/20 of the core biopsies, as examined by each hematopathologist, respectively, demonstrated 2 consistent cellularities. A median of 4 different cellularities were identified in each core. The mean range of cellularities of each core's portions was 43 4.6 %, and 46.5 4.9 %, as determined by the 2 hematopathologists, respectively, which was statistically equivalent (paired t-test p=0.349)

PURPOSE: To evaluate thalidomide in advanced hepatocellular carcinoma (HCC) and to evaluate combined thalidomide and low-dose interferon-alpha2a (IFN-alpha2a) after tumor progression on thalidomide. Systemic therapy is minimally effective in HCC and tumor angiogenesis is a potential therapeutic target. PATIENTS AND METHODS: Patients with unresectable HCC were eligible if they had preserved hepatic and renal function. The initial thalidomide dosage was 200 mg daily and was adjusted for toxicity. Upon progression, patients could continue thalidomide with additional low-dosage (one million units twice daily) IFN-alpha2a. RESULTS: Thirty-eight enrolled patients were predominantly hepatitis C virus infected (53%), Child-Pugh class A (79%), and Eastern Cooperative Oncology Group performance status 0-1 (92%); 60% had extrahepatic metastasis. Confirmed disease control was seen in seven patients (18%) and included one complete and one partial response (5% response rate). The median progression-free survival was 2.1 months, and median overall survival was 5.5 months. Tumor invasion of the portal vein or vena cava, large (>10 cm) tumor, and younger age were associated with shorter overall survival. Toxicity included fatigue in 74% of patients. Six patients stopped therapy because of side effects, including two patients (5%) with grade 4 arteriothrombotic events. Five patients continued thalidomide upon progression with the addition of IFN-alpha2a; there was no disease control and 80% had grade 3 toxicity. CONCLUSIONS: Thalidomide is not well tolerated and confers limited disease control in advanced HCC. Combination thalidomide and low-dose IFN-alpha2a is neither safe nor efficacious in this population

Breast involvement with non-Hodgkin's lymphoma (NHL) is rare. Patients with AIDS have an increased incidence of NHL, often with high-grade histology, extranodal presentation and aggressive clinical course. Lymphoma of the breast in patients with HIV-1 infection has not been reported. We reviewed our tumor registry database of all AIDS-associated NHL and report on the clinical presentation and long-term outcome of 3 patients with AIDS who presented with lymphomatous involvement of the breast