Lifestyle determinants and mortality in German vegetarians and health-conscious persons: results of a 21-year follow-up.

BACKGROUND: The long-term observation of vegetarians in affluent countries can provide insight into the relative effects of a vegetarian diet and lifestyle factors on mortality. METHODS: A cohort study of vegetarians and health-conscious persons in Germany was followed-up prospectively for 21 years, including 1,225 vegetarians and 679 health-conscious nonvegetarians. Standardized mortality ratios compared with the German general population were calculated for all causes and specific causes. Within the cohort, Poisson regression modeling was used to investigate the joint effects of several risk factors on overall and cause-specific mortality. RESULTS: Standardized mortality ratios for all-cause mortality was significantly below 100: 59 [95% confidence interval (95% CI), 54-64], predominantly due to a deficit of deaths from circulatory diseases. Within the cohort, vegetarian compared with nonvegetarian diet had no effect on overall mortality [rate ratio (RR), 1.10; 95% CI, 0.89-1.36], whereas moderate and high physical activity significantly reduced risk of death (RR, 0.62, 0.64), adjusted for age, sex, smoking, alcohol intake, body mass index, and educational level. Vegetarian diet was however associated with a reduced RR of 0.70 (95% CI, 0.41-1.18) for ischemic heart disease, which could partly be related to avoidance of meat. CONCLUSIONS: Both vegetarians and nonvegetarian health-conscious persons in this study have reduced mortality compared with the general population. Within the study, low prevalence of smoking and moderate or high level of physical activity but not strictly vegetarian diet was associated with reduced overall mortality. The nonsignificant reduction in mortality from ischemic heart diseases in vegetarians compared with health-conscious persons could be explained in part by avoidance of meat intake.     

Soft tissue sarcomas of the extremity

In 1955, in a series of abstracts entitled "A Half Century of Effort to Control Cancer," Pack and Ariel wrote, "in each individual case, there is a constant battle of judgement between the wisdom of more radical amputation and the need for preservation of that important functional part." This dilemma remains with us today. In his paper on the histogenesis of tumors, Stout, relating to the philosophy of treatment, wrote that "the best chance of curing malignant tumors of the soft tissues lies in the hands of the therapist who makes the first attempt." Pack's words are as true today as they were in 1955, and although limb salvage is possible for many patients with soft tissue sarcomas, preservation of an extremity at the risk of patient survival is not a feasible option. Most efforts at less than amputative surgery must entail multimodality therapy. Although there are some reports of success with single-agent therapy, such as surgery alone, the majority of successful, nonamputative series include surgery with radiation and/or chemotherapy. It must be emphasized that an extremely important aspect of the treatment of these patients is the judgment and evaluation by the primary physician. Therefore it is extremely important that the primary physician be familiar with the many factors involved in prognosis, both in terms of local control and of systemic illness, in order for the patient to be informed of treatment options. If this is not possible, the patient should be referred to a center that is involved in active research protocols or treatments. Although rare, the soft tissue sarcomas remain among the most difficult to treat, even though over the years there has been significant progress in diagnosis, classification, and successful local control. Patient survival is based on a multitude of factors that include the histogenesis of the tumor, its grade, size, anatomical location, the surgical procedure performed, the use of preoperative or postoperative radiation, and the clinical stage of the disease--whether it is primary or metastatic. In time, it is probable that additional factors will be found.     

Surgical Resection and Intraperitoneal Chemotherapy for Recurrent Abdominal Sarcomas

Background: Recurrent abdominal sarcomas have an extremely high rate of recurrence and poor overall survival. A prospective study was initiated to assess the feasibility, toxicity, and benefit of surgical resection and intraperitoneal chemotherapy for improving local control of disease and overall survival.Methods: Fifty-four patients underwent surgical excision of all gross disease and postoperative intraperitoneal chemotherapy with mitoxantrone. Thirty-five patients had peritoneal disease only (stage II), and 19 patients had peritoneal disease with hepatic metastases (stage III).Results: Nine (17%) patients remain free of disease with a mean follow-up of 37 months. The remaining 45 patients (83%) have had recurrence, with a mean interval to recurrence of 11 months. Stage (P 5.001) and grade (P 5.005) were the only two variables found to significantly affect recurrence. There was an overall peritoneal recurrence rate of 48% and an overall hepatic failure rate of 69%. Nineteen (35%) of the patients are alive, with a mean follow-up of 46 months. The overall 5-year survival was 31%. The 5-year survival for stage II patients was 46%; for stage III patients, it was only 5%. Stage (P 5.001) and grade (P 5.056) were the only two variables found to significantly affect survival. There were no treatment-related deaths, and only 5 patients (9%) developed local complications.Conclusions: Aggressive surgical resection and intraperitoneal chemotherapy for recurrent abdominal sarcomas is a feasible treatment approach with minimal toxicity. Although this treatment had little effect on the hepatic spread of this disease and thus overall survival, it appears to have significantly lowered the rate of peritoneal recurrence and may provide a survival benefit for patients with disease limited to the peritoneum.     

Cyclosporine as prophylaxis for graft-versus-host disease: a randomized study in patients undergoing marrow transplantation for acute nonlymphoblastic leukemia

Seventy-five patients, 13 to 49 years of age, with acute nonlymphoblastic leukemia in first remission were treated with cyclophosphamide, fractionated total body irradiation, and marrow transplantation from an HLA-identical sibling and randomized to receive either cyclosporine (CSP) (n = 36) or methotrexate (MTX) (n = 39) as prophylaxis for graft-v-host disease (GVHD). All patients engrafted, and 22 who were given CSP and 21 who were given MTX, are alive at 20 to 47 (median, 35) months (P = .5). Engraftment as assessed by granulocyte recovery (P less than .0005) and platelet transfusion requirement (P = .01) was faster in patients on CSP. Twelve patients (33%) on CSP and 22 (56%) on MTX developed acute GVHD of grades II through IV (P = .07) and 15 of 30 on CSP and 14 of 32 on MTX that were at risk developed chronic GVHD. The most frequent causes of death were interstitial pneumonitis and marrow relapse of leukemia, which occurred with similar frequency in both groups. Beneficial effects observed in patients on CSP included less severe mucositis and shorter duration of hospitalization; adverse effects included renal function impairment and hypertension. These data confirm that CSP is a useful immunosuppressant in patients undergoing marrow transplantation but fail to show a significant improvement in survival as compared with the standard regimen of MTX.     

Phase I trial of interleukin-2 after unmodified HLA-matched sibling bone marrow transplantation for children with acute leukemia

Allogeneic bone marrow transplantation (BMT) for advanced acute leukemia is associated with a high risk of relapse. It is postulated that interleukin-2 (IL-2) administered after BMT might induce or amplify a graft-versus-leukemia effect and thereby reduce the relapse rate. To identify an IL-2 regimen for testing this hypothesis, a phase I trial of IL-2 (Roche) was performed in children in complete remission (CR) without active graft-versus-host disease (GVHD) off immunosuppressive agents after unmodified allogeneic matched-sibling BMT for acute leukemia beyond first remission. Beginning a median of 68 days after BMT, 17 patients received escalating doses of induction IL-2 (0.9, 3.0, or 6.0 x 10(6) IU/m2/d representing levels I, II, and III) for 5 days by continuous intravenous infusion (CIV). After 6 days of rest, they received maintenance IL-2 (0.9 x 10(6) IU/m2/d) for 10 days by CIV infusion. Levels I and II were well-tolerated, but, of 6 patients at level III, 1 developed pulmonary infiltrates, 1 developed hypotension (both resolved), and 1 died of bacterial sepsis and acute respiratory distress syndrome. Grade II acute GVHD developed in 1 patient at level I and 1 at level III. The maximum tolerated dose of induction IL-2 was level II. IL-2 induced lymphocytosis, with an increase in CD56+ and CD8+ cells. Ten patients remain in CR at 5+ to 67+ months. Thus, a regimen of IL-2 has been identified that did not induce a high incidence of acute GVHD when administered to children after unmodified allogeneic BMT. Its clinical activity will be assessed in a phase II trial.     

Transplantation of allogeneic peripheral blood stem cells mobilized by recombinant human granulocyte colony-stimulating factor [see comments]

Peripheral blood stem cells (PBSCs) are widely used in autologous transplantation because of ease of collection and rapid hematopoietic reconstitution. However, PBSCs have rarely been used for allogeneic transplantation because of concerns about donor toxicities from cytokine administration and the theoretical increased risk of graft- versus-host-disease (GVHD) from the large number of T cells infused. Eight patients with advanced malignancies received allogeneic PBSC transplants from genotypically HLA-identical sibling donors. All donors received 5 days of recombinant human granulocyte colony-stimulating factor (rhG-CSF; 16 micrograms/kg/day) subcutaneously and were leukapheresed for 2 days. After treatment of the patient with total body irradiation and cyclophosphamide (n = 7) or etoposide, thiotepa, and cyclophosphamide (n = 1), PBSCs were infused immediately after collection and without modification. All patients received cyclosporine and either methotrexate (n = 6) or prednisone (n = 2) for GVHD prophylaxis, rhG-CSF was well tolerated with mild bone pain requiring acetaminophen occurring in two donors. All patients engrafted and in seven hematopoietic recovery was rapid, with 500 neutrophils/microL achieved by day 18 and 20,000 platelets/microL by day 12. Complete donor engraftment was documented by Y chromosome analysis in all four sex-mismatched donor-recipient pairs tested and by DNA analysis in two sex-matched pairs. One patient died on day 18 of veno-occlusive disease of the liver with engraftment but before chromosome analysis could be performed (results are pending in 1 patient). A second patient died of fungal infection 78 days after transplant. Grade 2 acute GVHD occurred in two patients and grade 3 GVHD occurred in one patient. One patient is 301 days from transplant in remission with chronic GVHD; the remaining five patients are alive and disease free 67 to 112 days after transplantation. Preliminary results indicate that allogeneic PBSCs mobilized by rhG-CSF can provide rapid hematologic recovery without an appreciably greater incidence of acute GVHD than would be expected with marrow. Further follow-up is required to determine the incidence of chronic GVHD and any potential beneficial effects on relapse after transplant.     

Allogeneic peripheral blood stem cell transplantation in patients with advanced hematologic malignancies: a retrospective comparison with marrow transplantation

Allogeneic peripheral blood stem cell (PBSC) transplants from HLA- identical siblings were performed in 37 patients with advanced hematologic malignancies. Outcomes were compared to a historical group of 37 similar patients with advanced hematologic malignancies receiving bone marrow (BM) transplants from HLA-identical donors. The PBSC group and historical BM group were well matched for diagnosis, disease stage, age, and graft-versus-host disease (GVHD) prophylaxis. Patients received PBSC transplants between 1993 to 1995 while BM patients were treated between 1989 to 1994. Engraftment, measured by the time to reach a peripheral neutrophil count > 500/L and platelet count > 20,000/microL without transfusions, occurred on days 14 and 11 in the patients transplanted with PBSC compared to days 16 and 15 in the patients receiving BM (P = .00063, .00014). The PBSC group required a median of 8 U of red blood cells and 24 U of platelets compared to 17 U of red blood cells and 118 U of platelets for BM transplant recipients (P = .0005, .0001). The estimated risks of developing grades 2 to 4 acute GVHD were 37% for the PBSC group and 56% for the BM group (P = .18), while the estimated risks of grades 3 to 4 acute GVHD were 14% for the PBSC group and 33% for the BM group, P = .05). Chronic GVHD occurred in 7 of 18 evaluable patients receiving PBSC and 6 of 23 evaluable patients receiving BM, P = .5. The estimated risks of transplant-related mortality at 200 days were 27% versus 45% (P = .33) relapse were 70% versus 53% (P = .27) and of overall survival were 50% and 41% (P = .39) for patients transplanted with PBSC or BM, respectively. This retrospective comparison suggests that compared to marrow transplantation from HLA-identical donors, allogeneic PBSC transplantation from HLA-identical donors is associated with faster engraftment, fewer transfusions, and no greater incidence of acute or chronic GVHD.     

Recurrence of aplastic anemia following cyclophosphamide and syngeneic bone marrow transplantation: evidence for two mechanisms of graft failure

Two patients with aplastic anemia were treated with high-dose cyclophosphamide and marrow transplantation from their normal, genetically identical twin. Both patients rapidly recovered normal marrow function, but marrow failure recurred 13 and 18 months later. Because donor and host pairs were identical twins, these cases of graft failure could not have resulted from the usual cause of graft failure, ie, immunological reactivity of host cells against unshared minor histocompatibility antigens of the donor. These results imply that there are at least two mechanisms responsible for graft failure after marrow transplantation for severe aplastic anemia.