Autotransplantation following busulfan, etoposide and cyclophosphamide in patients with non-Hodgkin's lymphoma.

The purpose of the study was to determine the toxicities and effectiveness of a novel preparative regimen of busulfan (Bu) 14 mg/kg, etoposide 50 or 60 mg/kg, and cyclophosphamide (Cy) 120 mg/kg in non-Hodgkin's lymphoma (NHL) and to analyze results using doses based on different body weight parameters and the two different etoposide doses. Three hundred and eighty-two patients aged 16 to 72 underwent first autologous transplantation with mobilized peripheral blood progenitor cells between August 1992 and December 1998 at either of two transplant centers. Mucositis was the most common toxicity. Hepatic toxicity was the most common life-threatening toxicity; severe hepatic VOD occurred in 11 patients (2.9%). Ten patients (2.6%) died from treatment-related toxicity. The 3-year progression-free survival (PFS) for the entire group was 46.9% (95% CI, 40.5-53.3%). Elevated LDH, resistance to chemotherapy, and intermediate/aggressive histology were significant adverse prognostic factors. For patients in sensitive first relapse PFS was 47.0% (95% CI, 37-57%). Neither etoposide dose nor body weight parameter utilized significantly affected outcome. In conclusion, the novel preparative regimen of Bu, etoposide and Cy results in a low incidence of treatment-related mortality and is effective in the treatment of patients with NHL. Bone Marrow Transplantation (2000) 25, 1243-1248.

Efficacy of color flow duplex imaging for proximal upper extremity venous outflow obstruction in hemodialysis patients.

PURPOSE: The efficacy of color flow duplex imaging (CFDI) in detecting proximal upper extremity venous outflow obstruction in hemodialysis patients was compared with that of traditional contrast venography. METHODS: From 1993 through 1997, all hemodialysis patients who were evaluated for upper extremity venous outflow obstruction of the axillary, subclavian, or brachiocephalic veins with both CFDI and venography were identified. Medical history, hemodialysis access procedures, and indications for imaging were reviewed. The diagnostic accuracy of CFDI was compared with that of venography for proximal venous outflow obstruction, including focal stricture, partial obstruction, or complete occlusion. RESULTS: Sixty upper extremities in 42 hemodialysis patients were imaged with both CFDI and venography. Previous ipsilateral intravenous dialysis catheters had been present in 33 (55%) of the extremities imaged; current catheters were present in 16 (27%) of the extremities imaged; and 28 (67%) of the extremities imaged had a current ipsilateral arteriovenous (AV) shunt. Five (8%) of the 60 duplex scans were nondiagnostic because of artifact from intravenous dialysis catheters (3) or incomplete visualization of the subclavian or brachiocephalic veins (2) and were excluded from further analysis. In the remaining 55 duplex scans, proximal venous outflow obstruction was found in 18 (33%), compared with 21 (38%) identified by means of venography (P = not significant [NS]). Overall sensitivity, specificity, positive predictive value, and negative predictive value for CFDI were 81%, 97%, 94%, and 89%, respectively. CONCLUSION: CFDI is a reliable means of detecting proximal upper extremity venous outflow obstruction and should replace contrast venography as the initial imaging study in hemodialysis patients.

Mobilization of peripheral-blood progenitor cells with high-dose etoposide and granulocyte colony-stimulating factor in patients with breast cancer, non-Hodgkin's lymphoma, and Hodgkin's disease.

PURPOSE: We analyzed the safety and effectiveness of high-dose etoposide (2 g/m2) followed by granulocyte colony-stimulating factor (G-CSF) as a peripheral-blood progenitor cell (PBPC) mobilization regimen and assessed extent of tumor reduction in patients with breast cancer, non-Hodgkin's lymphoma (NHL), and Hodgkin's disease (HD). PATIENTS AND METHODS: One hundred sixty-nine consecutive patients who eventually underwent PBPC transplantation received treatment with high-dose etoposide (2 g/m2) followed by daily G-CSF (5 microg/kg). RESULTS: This mobilization method was effective in nearly all patients. No patients died of mobilization-related complications. A 50% reduction in tumor size was seen in 19% of assessable patients with breast cancer, 44% of those with NHL, and 38% of those with HD. Hematopoietic recovery (HR) following transplantation occurred in all patients. Patients with > or = 4 x 10(6) CD34+ cells/kg engrafted with neutrophils at a median of 9 days after transplant and patients with at least 1.2 x 10(6) CD34+/CD33- cells/kg achieved platelet recovery at a median of 15 days. CONCLUSION: Etoposide plus G-CSF is an effective and safe method for mobilization of PBPCs. Etoposide is an effective agent in tumor reduction in NHL and HD and is less effective in breast cancer. The substantially lower incidence of prior exposure to this agent compared with cyclophosphamide favors its use.

Mechanical characteristics of dilated polytetraflouroethylene used for transluminally placed endovascular grafts.

This study was conducted to assess the mechanical characteristics of dilated polytetraflouroethylene (PTFE) for use in transluminally placed endovascular grafts (TPEGs). Ten-centimeter lengths of 3- and 4-mm thinwalled PTFE were dilated to 8, 10, 12, and 15 mm diameters (3 mm) and 10-, 14-, 16-, and 20-mm diameters (4 mm), respectively (n = 6 for each size). The dilated PTFE segments were evaluated for leakage, further dilation, structural changes (with electron microscopy), and changes in wall thickness occurring after 24 hours of perfusion at pressures of 300-350 mmHg. Both 3- and 4-mm thinwalled PTFE could be dilated to five times their initial diameter before rupture occurred. Three-millimeter grafts dilated to 12- and 4-mm grafts dilated to 14 mm remained resistant to leakage at perfusion pressures up to 350 mmHg. When 3-mm grafts were dilated to 15 mm, the PTFE leaked saline at a rate of 20.3 +/- 9.3 cc per hour at 300 mmHg. pressure. Four-millimeter grafts dilated to 16- and 20-mm diameters leaked saline at 8.4 +/- 7.8 and 52.8 +/- 22 cc per minute, respectively, at the same pressure. No grafts were found to increase in diameter after 24 hours of pressure perfusion. Electron microscopy revealed that PTFE node size was significantly smaller in dilated grafts than in undilated grafts, but there was no significant change in internodal distance. This data suggests that thinwalled PTFE can be dilated to large diameters and retain sufficient strength to resist supraphysiologic pressures. Long-term studies are needed to determine the late structural integrity of dilated PTFE.

Management of failed and infected axillofemoral grafts.

PURPOSE: The purpose of this study was to review the treatment of patients with failed or infected axillofemoral bypass grafts and to determine the efficacy of remedial procedures in maintaining graft patency and limb preservation. METHODS: Thirty-four patients with 37 failed or infected axillofemoral grafts were retrospectively reviewed. In nine cases there was no attempt at revascularization, and in the remaining 28 cases, a total of 52 remedial procedures was performed. Nine were performed in patients with graft infection and 43 in patients with graft thrombosis. In patients with axillofemoral graft failure, 21 thrombectomies, 13 graft revisions, and 9 secondary reconstructions were performed. Eighty-eight percent of patients were monitored at least 2 years or until graft failure. RESULTS: Eight of nine patients receiving no remedial procedure required major amputation. The limb salvage rate was 64% +/- 11% at 30 months in the 25 patients undergoing remedial procedures. Twenty-eight percent of failed axillofemoral grafts remained patent at 2 years after initial failure with single or multiple thrombectomies or revisions. Life-table primary patency after secondary reconstructions (81% +/- 10.9% at 24 months) was significantly better than after thrombectomy alone (10% +/- 4.2% at 24 months) or graft revision (16% +/- 10.6% at 24 months) by log-rank test (p < 0.001 and p < 0.005, respectively). Patients undergoing reconstruction with descending thoracic aorta to femoral artery bypass had an 89% +/- 11% patency rate at 24 months. Graft infection resulted in a perioperative mortality rate of 22% and amputation in 57% of survivors. CONCLUSION: Axillofemoral graft failure most often results in limb loss without remedial procedures. Thrombectomy and revision procedures had poor long-term patency rates and salvaged only a minority of grafts despite multiple procedures. Reconstruction by use of an alternate source of inflow such as the descending thoracic aorta resulted in better long-term patency rates in patients well enough to tolerate a major reoperative procedure.

Depletion of dietary arginine inhibits growth of metastatic tumor.

The effects of dietary arginine on the growth of a murine colon tumor metastatic to the liver were examined in a model of advanced neoplastic disease. Tumor growth was influenced by arginine both in vivo and in vitro. An arginine-supplemented diet stimulated tumor growth by 55% compared with controls. Conversely, an arginine-depleted diet inhibited tumor growth by 78% compared with controls. In vitro culture of both murine and human colon tumor cells confirmed that arginine was necessary for cell growth. Flow-cytometric analysis using propidium iodide and bromodeoxyuridine suggested that colon tumor cells cultured without arginine enter a quiescent S phase and depend on arginine for further growth and cell cycle progression. The potential roles for selective dietary arginine modulation in patients with cancer with advanced disease are discussed.