VAD Therapy Research Articles

Initial European experience with the lionheart(TM) LVAS (Left Ventricular Assist System)for destination therapy

aggregate adverse event rate was higher for LVAD pts (risk ratio 2.29 [95% CI 1.85-2.84]). Freedom from sepsis in LVAD pts was 55% at one year and 48% at two years post-implant with superior survival in non-septic pts (62% vs. 35% at 1 yr. and 41% vs. 7% at 2 yrs. in non-septic vs. septic LVAD patients [p 0.02]). Survival is improved with permanent VAD therapy compared to OMM for pts with severe HF who are not transplant candidates. However, infectious problems cause substantial morbidity and mortality in pts with permanently implanted LVADs. Decreasing infections will improve survival and decrease morbidity in permanent VAD recipients and will likley improve the risk-benefit ratio for permanent LVAD therapy.

Nonsecretory primary plasma cell leukemia successfully treated with VAD and MP therapy

Nonsecretory primary plasma cell leukemia successfully treated with VAD and MP therapy

Impact of complete remission with intensive therapy in patients with responsive multiple myeloma.

Clinical outcomes were assessed in 68 consecutive patients with multiple myeloma of high or intermediate tumor mass that had responded to VAD or dexamethasone-based therapy and were consolidated with early intensive therapy and autologous stem cell transplantation. Results were compared with those of 50 comparable patients who refused or were unable to receive intensive treatment for socioeconomic reasons. Following high-dose therapy, the rate of CR increased from 6 to 37%, with median survival prolonged by 10 months. Survival of 21 patients with disease converted from PR to CR (median 8.3 years) was significantly longer than that of similarly-treated patients who remained in PR (median 5.0 years). CR of myeloma represents the major surrogate marker of long survival and the primary goal of myeloablative treatment for patients in PR. Twelve of 18 patients with rapid reduction of myeloma protein (T(1/2) < 0.5 months), and myeloma protein reduction to <1.0 g/dl after primary therapy achieved CR (67%), identifying pretransplant features favorable to intensive therapy. Among 35 patients with slower reduction or higher residual myeloma protein, CR occurred in eight patients (23%) (P < 0.01), for whom other treatments should be considered. The kinetics of response to initial therapy should be considered in selecting patients more likely to achieve CR and consequent long survival after intensive treatment.

THE VENTRICULAR ASSIST DEVICE: An Overview

With the continuing shortage of available donor organs for cardiac transplantation, the use of the VAD has become a necessity in the treatment of heart failure. Organized efforts by the NIH allowed for the development of the prototypes of the devices that are used currently. There are five FDA-approved VADs for use as bridge to recovery or bridge to transplant indications. A thorough understanding of the physiology of the VAD and the basic concepts associated with VAD function is important in the management of these patients. Indications for use of VADs include cardiogenic shock from a potentially reversible cardiac insult, continued deterioration of cardiac transplant candidates despite maximal medical therapy, and as an alternative to cardiac transplantation. Patient selection and timing are crucial for good patient outcomes. Postoperative concerns of the VAD patient include fluid overload, inadequate preload, bleeding, tamponade, arrhythmias, and right heart failure. Postoperative nursing care supports hemodynamic stability, early ambulation, attention to respiratory concerns, and nutritional support. Long-term complications include infection and hypertension. Long-term nursing care includes education and emotional support. Future endeavors with VAD therapy surround the concept of destination therapy and refinement of the systems that are used currently to provide circulatory support.

Cyclophosphamide, etoposide, vincristine, adriamycin, and dexamethasone (CEVAD) regimen in refractory multiple myeloma: An international oncology study group (IOSG) phase II protocol

A 4- day continuous intravenous (CIV) infusion of vincristine and doxorubicin with high-dose dexamethasone (VAD) regimen is a standard refractory multiple myeloma (MM) regimen. A Phase II study of a CEVAD regimen, i.e., VAD plus etoposide administered as a 96-hr continuous infusion, was carried out with IV bolus cyclophosphamide. Thirty-six patients were treated on study and received a total of 114 cycles of CEVAD: median 2 cycles (range 1–8). No patient achieved a CR. The overall rate of PR was 15/36 (42%). Patients achieved maximal response after a median of 4 (range 3–6) courses. PR rates were 40% (4/10) in patients with primary refractory disease, 48% (11/23) in patients with secondary refractory disease, 31% (6/19) in patients who had failed previous VAD therapy, and 50% (7/14) in patients receiving 2nd or subsequent relapse therapy. Three patients died during their initial cycle of therapy from rapidly progressive disease and sepsis. Overall median survival was 24 weeks with a 1-year survival of 33.3% {95% confidence interval of 20–46%}. Myelosuppression was the most frequent adverse event with NCI grade 2 neutropenia and/or thrombocytopenia in 15% of first cycles, grade 3 in 20%, and grade 4 in 65%. Two-thirds of patients had at least one episode of grade 3 or 4 sepsis. In 15% of septic episodes positive blood cultures were obtained. Overt cardiotoxicity was seen in two patients. CEVAD as used in this study was not more effective than VAD in terms of overall response rate or survival. Am. J. Hematol. 63:125–130, 2000. © 2000 Wiley-Liss, Inc.

Myeloid markers in adult acute lymphocytic leukemia. Correlations with patient and disease characteristics and with prognosis.

The expression of myeloid markers on lymphoblasts has been associated with adverse outcome in acute lymphocytic leukemia (ALL). The purpose of the study was to analyze the experience with adults treated at the University of Texas M. D. Anderson Cancer Center with myeloid marker- (MY) positive ALL in relation to patient and disease characteristics, response to therapy, and prognosis. Since 1988, 64 of 162 adults (40%) with newly diagnosed ALL referred to our service had MY-positive ALL. Their characteristics and outcomes were compared with the 98 patients with MY-negative ALL. Patients were treated with the vincristine-doxorubicin-dexamethasone (VAD) regimens. Patients with MY-positive ALL were significantly older (median ages, 47 years vs. 33 years; P = 0.03), had a higher incidence of CD34 antigen expression (59% vs. 36%; P < 0.01), and a lower incidence of common acute leukemia antigen expression (50% vs. 71%; P < 0.01), serum alkaline phosphatase elevation (58% vs. 83%; P < 0.01), and thrombocytopenia at diagnosis (49% vs. 69%; P = 0.02). Myeloid marker positivity, as expected, was significantly higher in null cell ALL (82%), and significantly lower in mature B-cell ALL (17%) (P < 0.01). Forty-one of 64 MY-positive patients achieved complete remission (CR) after induction therapy compared with 76 of 98 patients MY-negative disease (CR rate 64% vs. 78%; P = 0.06). With a median follow-up of 45 months, no statistical differences were observed in remission duration or survival between MY-positive and MY-negative patients, overall, and within immunophenotypic subsets (T-cell vs. others), or among subgroups with single marker (CD13, CD14, CD33, CD34) positivity. The 3-year remission duration rates were 32% for MY-negative and 40% for MY-positive patients (P not significant), and 3-year survival rates were 26% and 31%, respectively (P not significant). With VAD therapy, myeloid marker positivity is not associated with significant differences in prognosis in adult ALL.

Results of the vincristine, doxorubicin, and dexamethasone regimen in adults with standard- and high-risk acute lymphocytic leukemia.

One hundred five untreated adult patients with acute lymphocytic leukemia (ALL) were entered on the vincristine, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and Decadron (dexamethasone; Merck Sharp and Dohme, West Point, PA) (VAD) regimen. Induction therapy with VAD and VAD plus cyclophosphamide (CVAD) was followed by a 2-year rotating maintenance program with multiple antileukemic combinations, and included early intensifications with Adriamycin and high-dose cytarabine (ara-C) and a late intensification with cyclophosphamide, carmustine (BCNU), and etoposide (VP-16) (CBV) followed by autologous bone marrow transplantation (BMT). Duration of therapy was 24 to 30 months. Eight-eight patients (84%) achieved complete remission (CR) with VAD-CVAD, and 94 (90%) ultimately had CR with continuation of the maintenance as planned. Induction mortality was 3%; only half of the patients required prolonged hospitalization of 1 week or longer, or intravenous antibiotics. Maintenance therapy was given to 79 patients, while nine with histocompatibility locus antigen (HLA)-matched related donors underwent allogeneic BMT. The median remission duration was 22 months, and the median survival was 19 months. Factors associated with significantly worse CR rates were older age, the presence of hypoalbuminemia or hyperbilirubinemia, L2 or L3 morphology, and myeloid markers on leukemic cells. Those associated with significantly worse remission durations were the presence of elevated leukocyte or absolute peripheral blast counts, Philadelphia chromosome (Ph)-positive or B-cell ALL, L2 morphology, and more than one course to achieve CR. Patients could be divided into standard-risk ALL (28% of patients) and high-risk ALL (72% of patients) with long-term remission rates of 70% versus less than 30%. The 26 patients who underwent CBV autologous BMT had similar long-term outcome compared with 21 patients who did not (older age, medical contraindications, or socioeconomic problems). The presence or absence of myeloid markers on leukemic cells did not affect long-term prognosis. We conclude that VAD therapy is a well-tolerated effective induction regimen. High-risk ALL patients require alternative maintenance investigational approaches.

VAD chemotherapy—toxicity and efficacy—in patients with multiple myeloma and other lymphoid malignancies

Thirty-three patients with multiple myeloma (11 untreated, 15 refractory and seven relapsed patients) have received vincristine and adriamycin infusion therapy with oral dexamethasone (VAD). The median number of course received was five. In addition 16 patients with lymphoid malignancy have received a median of four courses of VAD. Three patients who relapsed after VAD have received further VAD therapy making 52 patient treatments assessable for toxicity. Ten per cent had nausea, 4 per cent vomiting, 4 per cent total alopecia, 25 per cent constipation, 33 per cent paraesthesiae, 8 per cent proximal myopathy, 33 per cent dyspepsia, 23 per cent proven bacteraemia, and 19 per cent chest infections. Infections were not usually associated with neutropenia. Shingles was seen in four patients with myeloma, but none of the patients with lymphoid malignancy. The response rate in myeloma was 9/11, for previously untreated patients, 3/7 for relapsed, and 8/15 for refractory patients. Responses have been seen in other lymphoid malignancies-1/2 patients with relapsed acute lymphoblastic leukaemia had a complete remission. Two out of seven patients with chronic lymphocytic leukaemia achieved a partial remission, and a further three had a clinical improvement. Three out of six patients with non-Hodgkin lymphoma and one patient with macroglobulinaemia achieved a partial remission.