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This phase 1 study (clinical trial NCT00477815) was conducted to determine the maximum tolerated dose (MTD) of yttrium-90 ibritumomab tiuxetan (90Y-Zevalin) with high dose melphalan (HDM) therapy in multiple myeloma (MM) patients undergoing autologous stem cell transplantation (ASCT). In a 3+3 trial design, 30 patients received rituximab 250 mg/m2with indium-111 ibritumomab tiuxetan (111In-Zevalin) for dosimetry (day −22); rituximab 250 mg/m2with escalating doses of 90Y-Zevalin (day −14); melphalan 100 mg/m2(days −2,−1) followed by ASCT (day 0) and sargramostim (GM-CSF, day 0) until neutrophil engraftment. Each patient’s 111In-Zevalin dosimetry data were used to calculate the dose of 90Y-Zevalin (in mCi) to deliver 10, 12, 14, 16, 18 or 20 Gy to the liver. Dose limiting toxicities were seen in 3 patients. The overall response rate was 73% (22/30) with stringent complete response in 2 patients; complete response, 5; very good partial response, 12; and partial response, 3. The median PFS was 16.5 months and the median overall survival was 63.4 months. In MM, the MTD of 90Y-Zevalin with HDM is 18 Gy to the liver. The addition of radiation with novel delivery methods such as radioimmunotherapy combined with standard transplant regimens warrants further study.

Thalidomide is a glutamic acid derivative initially introduced as a sedative hypnotic nearly forty years ago. It was withdrawn following numerous reports linking it to a characteristic pattern of congenital abnormalities in babies born to mothers who used the drug for morning sickness. It has gradually been re‐introduced into clinical practice over the past two decades, albeit under strict regulation, since it was found to be useful in the management of erythema nodosum leprosum and HIV wasting syndrome. Recognition of its anti‐angiogenic effect led to its evaluation in the treatment of various malignancies, where angiogenesis has been shown to play an important role. Numerous clinical trials done over the past four years have confirmed the significant anti‐myeloma activity of this drug. It has also shown promise in preliminary trials in the treatment of a variety of different malignant diseases. The mechanisms of its antineoplastic effects continue to be the focus of ongoing research. It has become clear that even though its anti angiogenic effects play a significant role in the anti‐tumor activity, there are other properties of this drug which are responsible as well. It also possesses anti‐TNF alpha activity, which has led to its evaluation in several inflammatory states. In this concise review, we briefly describe the historical background and pharmacological aspects of this drug. We have concisely reviewed the current knowledge regarding mechanisms of its anti‐neoplastic activity and the results of various clinical trials in oncology.

Angiogenesis is the formation of new blood vessels and occurs physiologically during embryonal growth, wound healing and during the menstrual cycle. It is essential for the proliferation and metastases of most malignant neoplasms. Recent evidence suggests that angiogenesis is increased in multiple myeloma and has prognostic value in the disease. Angiogenic cytokines such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor are expressed by myeloma cells and appear to play a role in the increased angiogenesis seen in myeloma. In addition, VEGF may serve as a paracrine growth factor for myeloma cells. Based on the increased angiogenesis observed in myeloma, thalidomide has been studied as antiangiogenic therapy. Although its mechanism of action in myeloma is still unclear, thalidomide appears to be active in 25–30% of patients with refractory myeloma. Major toxicities include constipation, sedation, skin rash, fatigue, and peripheral neuropathy. Studies are ongoing to determine its role as initial treatment for myeloma. This paper reviews the available data on angiogenesis in myeloma, and summarizes the role of thalidomide therapy in this disease. The pharmacology and toxicity of thalidomide are also discussed. Copyright 2000 Harcourt Publishers Ltd

We describe 9 patients who presented with a neoplastic meningitis of lymphomatous origin. No evidence of parenchymal central nervous system or systemic tumor was identified either at the time of presentation or throughout the course of their disease. We have chosen to call this entity “primary leptomeningeal lymphoma” (PLML). This unusual form of neurologic lymphoma must be differentiated from the more common clinical situations of primary parenchymal lymphoma with meningeal involvement and systemic lymphoma complicated by lymphomatous meningitis.

PURPOSE: This study was designed to evaluate the clinical characteristics, surgical treatment, and outcome of carcinoid tumors of the rectum and to assess flow cytometry deoxyribonucleic acid (DNA) analysis as a potential prognostic factor for management of these tumors. METHODS: Medical records, tumor registry database, and pathology slides were retrospectively reviewed. Flow cytometry DNA analysis was performed on archived specimens. RESULTS: One hundred nine patients with rectal carcinoid tumors underwent surgery between 1962 and 1987. Follow-up was available in 86 patients for a mean period of 12 years. Of 100 patients with tumors less than 2 cm, only one with a 1.5 cm ulcerated tumor developed liver metastases. Of nine patients with a tumor more than or equal to 2 cm, three with known liver metastases underwent rectal biopsy only, and three had rectal biopsy and laparotomy with biopsy of liver metastases. Three patients underwent radical resection. Following abdominoperineal resection, one patient died with local recurrence after 5 years, and one developed hepatic recurrence after 5.5 years and died at 9 years. One patient with coloanal anastomosis developed local and hepatic metastases seven years after surgery and died at ten years. No patients developed carcinoid syndrome. DNA ploidy did not correlate with metastases at presentation or recurrence of carcinoid tumor. CONCLUSION: Radical resection of rectal carcinoids with ulceration or size greater than or equal to 2 cm is associated with a poor prognosis; however, survival may be long term, even in the presence of metastatic disease. DNA ploidy does not appear to be a useful prognostic factor for rectal carcinoid tumors.

Peripheral blood mononuclear cells from 11 patients with untreated B-chronic lymphocytic leukemia (CLL) were exposed to sodium phenylacetate (NaPA) in culture to assess its ability to induce differentiation. We found no evidence of cellular differentiation or induction of tartrate resistant acid phosphatase activity, as seen when B-CLL cells were treated with phorbol ester. We observed a striking decrease in the viability of the B-CLL cells in a time and dose dependent fashion when exposed to NaPA. After six days of culture, control cells from the 11 patients studied had a median viability of 90%, whereas cells exposed to NaPA at 5 and 10 mM concentrations had median viabilities of 39 and 16%, respectively. The cells treated with NaPA developed prominent cytoplasmic vacuoles. NaPA binds and depletes glutamine which is an important amino acid for lymphocyte metabolism. Although the mechanism of the cytocidal effects demonstrated in this study are unknown, they may relate at least partially to glutamine deprivation.

Background: Although the association between large uterine fibromyomas and secondary polycythemia has been described previously, the mechanism has not been elucidated definitively. Investigators have measured erythropoietin levels in fibromyomas to determine whether these tumors are causing the polycythemia by erythropoietin overproduction; however, these studies were performed before the availability of recombinant erythropoietin assays.