Fludarabine phosphate and melphalan: a reduced intensity conditioning regimen suitable for allogeneic transplantation that maintains the graft versus malignancy effect.

Reduced intensity conditioning (RIC) for allogeneic stem cell transplantation allows stable donor cell engraftment with the maintenance of a graft versus malignancy effect. Many different regimens exist employing various combinations of chemotherapy, radiotherapy and T-cell depletion. We examined the role of non-T-cell depleted RIC regimens in 56 patients with haematological malignancies. Patients received fludarabine phosphate for 5 days (30 mg/m2 in 35 patients, 25 mg/m2 in 21 patients) and melphalan for 1 day (140 mg/m2 in 36 patients, 100 mg/m2 in 20 patients). Immunosuppression was with CyA alone in 33 patients and CyA/MTX in 23 patients. Twenty-four of the 26 patients with chimerism data showed >95% donor chimerism at 3 months post transplant. aGVHD occurred in 18% of patients receiving CyA/MTX compared to 53% of patients receiving CyA. The 100-day mortality rate was 0.16 (95%CI 0.08-0.28) and 1-year nonrelapse mortality was 0.24 (95%CI 0.13-0.38). Thirty-three patients remained alive and in CR at a median of 19 months post transplant (range 3-38 months). We have shown that patients transplanted with fludarabine phosphate, melphalan 100 mg/m2 and with CyA/MTX as post transplant immunosuppression can achieve good disease control with an acceptable level of toxicity. Further studies are required to confirm these findings.

FLUDAP: salvage chemotherapy for relapsed/refractory aggressive non-Hodgkin's lymphoma.

The aim of this study was to investigate the combination of fludarabine phosphate, dexamethasone, cytosine arabinoside and cis-platinum (FLUDAP) in the treatment of patients with relapsed/refractory aggressive non-Hodgkin's lymphoma (NHL). This regimen comprises: dexamethasone 100 mg/d continuous infusion (cont. inf.) d1-3; cytosine arabinoside (ara-C) 1 g/m2/d cont. inf. d 2,3; fludarabine phosphate 30 mg/m2 short inf. 4hr prior to each 24hr ara-C inf.; cis-platinum 50 mg/m2 4hr inf. at the start of each 24hr ara-C inf. G-CSF (lenograstim, Granocyte) is given at 263 microg s.c. daily from day 7 until the neutrophil count reaches 1.0x10(9)/l. The regimen repeats at 21 day intervals. A total of 33 patients were registered (median age 47 years; 24 males, 9 females); the majority (73%) were refractory to their previous treatment and most had advanced disease by Ann Arbor stage. Thirteen (39%) of the 33 enrolled patients (52% of the 25 fully evaluable patients who received at least 2 courses of FLUDAP) responded to treatment. A maximum response of complete remission was achieved in 5 patients, good partial remission in 3, and partial remission in 5. Twelve patients went on to successful stem cell supported intensification therapy. Median survival times were higher in the responding patients, and in those patients transplanted post-FLUDAP. The toxicity associated with the FLUDAP regimen was generally predictable; frequently reported severe events included haematological toxicity and infection. In conclusion, the FLUDAP regimen shows promise as a salvage regimen and increases the available therapeutic options in the treatment of recurrent/refractory aggressive NHL.

Antiplatelet drugs and the incidence of thromboembolic complications of the St. Jude Medical aortic prosthesis in patients with rheumatic heart disease.

The incidence of thromboembolic complications after St Jude Medical aortic valve replacement was evaluated in patients who received antiplatelet drugs alone (aspirin and dipyridamole). This report includes 107 consecutive patients undergoing aortic valve replacement with the St. Jude Medical prosthesis from February, 1980, until December, 1983. There were three perioperative deaths (2.8%). Thirty-seven of these patients received life-time warfarin anticoagulation and therefore were excluded from further analysis. The remaining 67 patients receiving antiplatelet drugs were followed up for 22 +/- 8 months (range 5 to 54 months) with a total observation period of 123 patient-years. Group 1 consisted of 52 patients having single St. Jude Medical aortic valve replacement (mean age 27 +/- 10 years). Group 2 included 15 patients having St. Jude Medical aortic valve replacement with additional mitral valve replacement (mean age 27 +/- 11 years). There were no postoperative embolic events in Group 1, but two St. Jude Medical aortic prostheses became thrombotic (2.1 per 100 patient-years) 19 and 32 months after the operation. Emergency aortic valve replacement was done in one of these patients and aortic thrombectomy in the other. Both patients are alive and doing well. In Group 2, three patients (10 per 100 patients-years) had thrombosis of the St. Jude Medical aortic valve 10, 12, and 30 months after the operation, and two of them required emergency aortic value replacement. One of these patients also had a massive left coronary embolus and could not be weaned from cardiopulmonary bypass. The third patient, who was asymptomatic, was prescribed warfarin anticoagulation and has been well. None of the seven patients in this group with St. Jude Medical aortic and mitral prostheses has had a thromboembolic event. These results indicate that antiplatelet drugs alone are associated with a very low risk of embolism but are insufficient to prevent thrombosis of St. Jude Medical aortic valves, even when the patients have sinus rhythm.

Left heart decompression via the pulmonary artery.

A technique of left heart decompression is presented which is simple and easy to apply. Cannulation of the main pulmonary artery with a coiled wire reinforced venous cannula provides access for continuous suction and effectively decompresses both the left and right sides of the heart. An in-line vacuum release valve controls the amount of suction.

Percutaneous transluminal angioplasty of a large septal artery.

A severely stenotic, large-caliber, first septal artery was successfully dilated in a patient with refractory angina and nonsurgical, multivessel coronary artery disease. The success of this dilatation was related to favorable coronary anatomy and to the availability of a guidewire-directed dilatation catheter. Septal artery stenosis with or without surgically accessible stenoses in other coronary vessels represents a potential indication for percutaneous transluminal coronary angioplasty.

Biologic reconstruction of the right ventricular outflow tract. Preliminary experimental analysis and clinical application in a neonate with type I truncus arteriosus.

A unique concept of right ventricular outflow tract reconstruction is presented. Applications of this concept, employing a glutaraldehyde-preserved heterograft mitral valve leaflet mounted directly to the right ventricle, was studied in six immature goat models. Interval evaluation of these models demonstrated no significant outflow tract obstruction or aneurysm. Only one animal had significant pulmonary outflow regurgitation angiographically at the time of sacrifice. All heterograft valve leaflets showed a degree of calcification and/or retraction directly related to the time interval between implant and sacrifice. Encouraging early results were obtained with this method of pulmonary outflow tract reconstruction in a 2,400 gram neonate with type I truncus arteriosus.

Septal wall motion. Its significance on outcome of left ventricular scar resection.

To assess the importance of septal wall motion on patient outcome after resection of large akinetic and dyskinetic segments of left ventricle, the records of 70 patients undergoing left ventricular scar excision alone or in combination with myocardial revascularization procedures between January 1970 and January 1977 were reviewed. Patients requiring simultaneous prosthetic valve replacement were excluded. Preoperative left anterior oblique ventriculograms categorized this series of patients into two distinct groups, group A (36 patients) having normal septal wall motion and group B (34 patients) having akinetic or dyskinetic septal walls. Indications for operation and preoperative ejection fractions were similar in both groups. Analysis of these patients subjected to surgery with and without preoperative evidence of septal wall motion demonstrated no significant difference in either functional clinical capacity or in mortality. Mortality for both groups was 11%. Absence of ventricular septal wall motion has no significant effect on outcome of left ventricular scar resection and should not be used as a contraindication to surgery.

Current status of prosthetic cardiac valves.

The majority of patients with acquired valvular heart disease have severe damage to valves which is not amenable to repair but can now be treated by valve replacement with an acceptable mortality and morbidity. The caged ball or disc valve is widely used and is proving clinically satisfactory for cardiac valve replacement. Thromboembolism is the significant complication. With improvement in technique the incidence of infection, detachment and other complications has been reduced.