Transplantation of peripheral blood progenitor cells from HLA-identical sibling donors. European Group for Blood and Marrow Transplantation (EBMT)

Transplantation of peripheral blood progenitor cells (PBPCs) has largely replaced autologous bone marrow transplantation. The same might occur in the allogeneic setting if the favourable initial experience with allogeneic PBPCT is confirmed. We analysed all primary transplants utilizing unmodified PBPC from HLA-identical sibling donors reported to the European Group for Blood and Marrow Transplantation (EBMT) for 1994. 59 patients with a median age of 39 years received myeloablative therapy for acute myelogenous leukaemia (23 patients, acute lymphoblastic leukaemia (13), chronic myelogenous leukaemia (nine), lymphoma (seven), or other diagnoses (seven) mostly of advanced stages followed by transplantation of allogeneic PBPC. Three patients died soon after grafting, the others showed prompt haemopoietic recovery with median times to recover an absolute neutrophil count (ANC) above 0.5 and 1.0 x 10(9)/I of 15 (range 9-27) and 17d (range 10-28) respectively. Time to platelet recovery above 20 or 50 x 10(9)/I was 16 (range 9-76) and 18d (range 12-100) respectively. 27 patients (46%) developed no or mild acute graft-versus-host disease (GVIID). The incidence of moderate (grade II) disease was 27%; 24% of the patients developed severe acute GVHD (grades III or IV), 55% of patients who were alive 90d after transplantation developed chronic GVHD, the probability to develop extensive chronic GVHD was 32% (95% confidence interval 22-42) with a median follow-up of 14 months. Overall and event-free survival (EFS) at 1 year were 54% (CI 48-60) and 50% (CI 43-57), respectively, the relapse incidence was 23% (CI 17-29). EFS was 67% (CI 55-79) in patients transplanted for acute leukaemias in first complete remission, chronic myelogenous leukaemia in first chronic phase, or severe aplastic anaemia. Transplantation of allogeneic PBPC resulted in prompt and durable engraftment. The incidence and severity of acute and chronic GVHD seemed comparable to that observed after allogeneic BMT. Overall and event-free survival in this cohort of patients, most of whom suffered from advanced leukaemia or lymphoma, is encouraging, suggesting that the high numbers of T lymphocytes and/or natural killer cells contained in a typical PBPC collection product exert a vigorous graft-versus-leukaemia effect. Further evaluation of allogeneic PBPCT is highly desirable.     

Incidence and outcome of hepatic veno-occlusive disease after blood or marrow transplantation: a prospective cohort study of the European Group for Blood and Marrow Transplantation. European Group for Blood and Marrow Transplantation Chronic Leukemia Working Party

To determine the incidence and outcome of hepatic veno-occlusive disease (VOD) after blood or marrow transplantation (BMT), we prospectively evaluated all consecutive patients receiving a BMT during a 6-month period in participating EBMT centers. All of them were evaluated for occurrence of VOD according to previously defined clinical criteria. The clinical course, outcome, value of prophylactic and therapeutic interventions, and the influence of previously described risk factors were analyzed. During the study period, 1,652 BMT were performed in 73 centers. VOD was diagnosed in 87 patients (5.3%; 95% confidence interval [CI], 4.2% to 6.4%). Fifty-six of 631 allogeneic BMT (8.9%) and 31 of 1,010 autologous BMT (3.1%) developed this complication (P <.0001). VOD was classified as mild in 7 (8%), moderate in 56 (64.4%), and severe in 24 (27.6%) cases. Sixteen patients died of VOD (corresponding to 1% of the whole series, 18.4% of VOD patients, and 66.7% of severe VOD). The use of unfractionated heparin did not significantly decrease the incidence of VOD. Independent variables associated with an increased risk of VOD were allogeneic BMT (relative risk [RR], 2.8; P <.001), pre-BMT elevation of serum aspartate aminotransferase (RR, 2.4; P =.001), high-dose cytoreductive therapy (RR, 2.3; P =.003), Karnofsky performance score less than 90% (RR, 2.7; P =.006), and prior abdominal radiation (RR, 2.9; P =.03). In conclusion, this prospective study shows that (1) the incidence of VOD is lower than that reported in smaller studies from single centers, (2) about one fourth of cases of VOD progress to severe disease, (3) main risk factors have a major impact on incidence of VOD, and (4) the use of prophylactic unfractionated heparin does not seem to reduce the incidence of VOD.     

Transplantation of hematopoietic stem cells. II: Indications for transplantation of hematopoietic stem cells after myeloablative therapy

The destruction of hematopoiesis and lymphopoiesis by total body irradiation or high dose chemotherapy for the treatment of malignancy can be reversed by the transplantation of allogeneic or autologous hematopoietic stem cells. In primary disorders of bone marrow or immune system, allogeneic stem cells replace deficient cells. Acute leukemias can be cured, with in 50 to 80% disease free survival after 5 to 8 years. The allogeneic graft versus leukemia effect by immunoreactive cells reduces the relapse rate in myeloid and lymphoid malignancies. 40 to 70% of patients with chronic myeloid leukemia remain disease free after more than 5 years. Patients with malignant lymphoma have a 40 to 70% chance of cure with autologous transplantation, which is not increased by allogeneic cells, because of a higher incidence of severe complications. An increasing number of patients without option for cure is treated with the aim of prolonging remission or retarding disease progression, such as in chronic myeloid leukemia, multiple myeloma and certain solid tumors. New studies suggest in breast cancer with axillary lymph node metastases, that adjuvant high dose chemotherapy with autologous stem cell support will significantly improve disease free survival from 30 to over 60% after 3 to 5 years. In congenital metabolic and storage diseases deficient enzymes are substituted by the allogeneic cells. Clinical trials explore the use of stem cell transplantation after myeloablative therapy in autoimmune disorders as well as in gene therapy with transfected hematopoietic stem cells.     

Long-term results after allogeneic bone marrow transplantation for chronic myelogenous leukemia in chronic phase: a report from the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation

The purpose of this study was to determine the long-term results of allogeneic bone marrow transplantation for chronic myeloid leukemia. A retrospective analysis was carried out of the outcome of 373 consecutive transplants performed at 38 European institutions between 1980 and 1988 and reported to the registry of the European Group for Blood and Marrow Transplantation. All transplants were carried out for first chronic phase of chronic myelogenous leukemia using unmanipulated marow cells from HLA-identical sibling donors. The probability of survival and leukemia-free survival at 8 years were 54% (95% CI: 49-59) and 47% (95% CI: 41-52) respectively. The probabilities of developing acute GVHD (II-IV) at 100 days and chronic GVHD at 4 years after transplant were 47% (95% CI: 41-53) and 52% (95% CI: 46-58) respectively. The probabilities of transplant-related mortality and leukemic relapse 8 years after BMT were 41% (95% CI: 36-48) and 19% (95% CI: 14-25), respectively. Transplant within 12 months of diagnosis was associated with reduced transplant-related mortality (34 vs 45%, P = 0.013) and resulted in improved leukemia-free survival (52 vs 44%, P = 0.03). The probability of relapse was significantly reduced in patients who developed chronic GVHD (RR = 0.33, P = 0.004). The probability of relapse occurring more than 2 years after transplant was increased more than five-fold in patients transplanted from a male donor (RR = 5.5, P = 0.006). Sixty-seven patients in hematologic remission were studied for residual disease by two-step RT/PCR for BCR-ABL mRNA and 61 (91%) tested negative. We conclude that bone marrow transplantation can induce long-term survival in approximately one-half of CML patients; the majority of survivors have no evidence of residual leukemia cells when studied by molecular techniques. The probability of late relapse is increased with use of a male donor.     

Granulocytic sarcoma after allogeneic bone marrow transplantation: a retrospective European multicenter survey. Acute and Chronic Leukemia Working Parties of the European Group for Blood and Marrow Transplantation

In the newly established rat sarcoma cell line LSR-SF (SR) expression of pp60v-src was detected. Karyotype analyses revealed various chromosome aberrations during prolonged passaging of the tumor cells in vitro. Polyploidy was found to be a characteristic feature of the line studied. A large metacentric chromosome persistently present in the cells was accepted as a line marker.     

Cataracts after total body irradiation and bone marrow transplantation in patients with acute leukemia in complete remission: a study of the European Group for Blood and Marrow Transplantation

PURPOSE: Advances in bone marrow transplantation (BMT) have consistently improved long-term survival. Therefore, evaluation of late complications such as cataracts is of paramount importance. METHODS AND MATERIALS: We analyzed data of 2149 patients from the EBMT registry. A cohort of 1063 patients were evaluable for survival and ophthalmologic status after transplant for acute leukemia (AL) in first or second complete remission. Conditioning therapy included either single-dose total body irradiation (STBI) or fractionated TBI (FTBI) grouped in different dose rates (low: LDR < or = 0.04 Gy/min; high: HDR > 0.04 Gy/min). RESULTS: The overall 10-year estimated cataract incidence (ECI) was 50%. It was 60% in the STBI group, 43% in the FTBI group < or = 6 fractions, and 7% in the FTBI group > 6 fractions (p < 10(-4)). It was significantly lower (30%) in the LDR than in the HDR groups (59%;p < 10(-4)). Patients receiving heparin for veno-occlusive disease prophylaxis had fewer cataracts than those who did not (10-year ECI: 33% vs. 53%, respectively;p = 0.04). The 10-year ECI was 65% in the allogeneic vs. 46% in the autologous BMT patients (p = 0.0018). Factors independently associated with an increased risk of cataract were an older age (> 23 years), higher dose rate (> 0.04 Gy/min), allogeneic BMT, and steroid administration (> 100 days). The use of FTBI was associated with a decreased risk of cataract. Heparin administration was a protective factor in patients receiving STBI. In terms of cataract surgery, the unfavorable factors for requiring surgery were: age > 23 yr, STBI, dose rate > 0.04 Gy/min, chronic graft-vs.-host disease (cGvHD), and absence of heparin administration. Among the patients who required cataract surgery (111 out of 257), secondary posterior capsular opacification was observed in 15.7%. CONCLUSION: High dose rate and STBI are the main risk factors for cataract development and the need for surgery, and the administration of heparin has a protective role in cataractogenesis.     

Allogeneic bone marrow transplantation vs filgrastim-mobilised peripheral blood progenitor cell transplantation in patients with early leukaemia: first results of a randomised multicentre trial of the European Group for Blood and Marrow Transplantation

In a multicentre trial involving 20 transplant centres from 10 countries haematopoietic stem cells were obtained either from the bone marrow of 33 sibling donors or from the peripheral blood of 33 such donors after administration of filgrastim (10 microg/kg/day). The haematopoietic stem cells were infused into their HLA-identical recipients suffering from acute leukaemias in remission or chronic myeloid leukaemia in chronic phase. PBPC donors tolerated filgrastim administration and leukapheresis well with the most frequent side-effects being musculoskeletal pain, headache, and mild increases of LDH, AP, Gamma-GT or SGPT. Pain and haematoma at the harvest site and mild anaemia were the most frequent complaints of BM donors. Severe or life-threatening complications were not seen with any type of harvest procedure. Time to platelet recovery greater than 20 x 10(9)/l was 15 days (95% confidence interval (CI) 13-16 days) in the PBPCT group and 19 days (CI 16-25) in the BMT group. Time to neutrophil recovery greater than 0.5 x 10(9)/l was 14 days (CI 12-15 days) in the PBPCT group as compared to 15 days (CI 15-16 days) in the BMT group. The numbers of platelet transfusions administered to PBPCT and BMT patients were 12 (range: 1-28) and 10 (range: 3-39), respectively. Sixteen patients (48%) transplanted with bone marrow and 18 patients (54%) transplanted with PBPC developed acute GVHD of grades II-IV; acute GVHD of grades III or IV developed in six (18%) and seven (21%) patients, respectively. Kaplan-Meier plots for transplant-related mortality until day 100 and leukaemia-free survival at a median of 400 days after BMT or PBPCT showed no significant differences. Administration of filgrastim and leukapheresis in normal donors were feasible and well tolerated. The number of days with restricted activity and of nights spent in hospital was lower in donors of PBPC. Transplantation of PBPC to HLA-identical siblings with early leukaemia resulted in earlier platelet engraftment. The incidence of moderate to severe acute GVHD, transplant-related mortality, and leukaemia-free survival did not show striking differences. Further investigation of allogeneic PBPCT as a substitute for allogeneic BMT is warranted.     

Autologous bone marrow transplantation for patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia following MDS. Chronic and Acute Leukemia Working Parties of the European Group for Blood and Marrow Transplantation

Intensive chemotherapy followed by autologous bone marrow transplantation (ABMT) may provide an alternative therapy for young patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia following MDS (sAML) lacking a suitable donor. We report the results for 79 patients with MDS/sAML transplanted with autologous marrow in first complete remission (CR). Within the total group of 79, a cohort of 55 patients for whom the duration of first CR was known were compared with a matched control group of 110 patients with de novo AML. The 2-year survival, disease-free survival (DFS), and relapse rates for the 79 patients transplanted in first CR were 39%, 34%, and 64%, respectively. The relapse risk was greater than 55% for all stages and all disease categories. Patients younger than 40 years had a significantly (P = .04) better DFS (39%) than patients older than 40 years (25%). The DFS at 2 years was 28% for the cohort of 55 patients transplanted for MDS/sAML and 51% for those transplanted for de novo AML (P = .025). Relapse rates were 69% for patients with MDS/sAML and 40% for those with de novo AML (P = .007). ABMT for MDS or secondary leukemia results in a lower DFS when compared with similarly treated patients with de novo AML due to a higher relapse rate. The DFS of 28% for these patients suggests that autotransplantation may be a valuable therapy for this disease. The low treatment-related mortality rate of less than 10% supports the view that sufficient numbers of hematopoietic stem cells are present in patients with MDS to allow adequate repopulation after autologous stem-cell transplantation.     

Risk assessment for patients with chronic myeloid leukaemia before allogeneic blood or marrow transplantation. Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation

BACKGROUND: Transplantation of blood or bone-marrow stem cells is the treatment of choice for selected patients with chronic myeloid leukaemia (CML). Transplantation is used with increasing frequency and success, but remains associated with substantial risks of morbidity and mortality. Other treatments with satisfactory short-term outcome are available. For appropriate counselling of patients, a rapid and simple way to assess risk is needed. METHODS: Data from 3142 patients (1873 [60%] male, 1269 [40%] female; mean age 34 years, range <1-60 years) treated with allogeneic blood or marrow transplants for CML between 1989 and 1997, reported to the European Group for Blood and Marrow Transplantation (EBMT), were used to develop and test a simple risk score based on previously reported major pretransplant risk factors: histocompatibility, stage of disease at time of transplantation, age and sex of donor and recipient, and time from diagnosis to transplantation. We analysed probabilities of survival, leukaemia-free survival, transplant-related mortality, and relapse incidence with respect to these risk factors. FINDINGS: At the time of analysis, 1922 (61%) of the 3142 patients were alive-1567 (65%) of those with HLA-identical sibling donors and 417 (57%) of those with unrelated donors. 1682 (54%) were alive without relapse. 1220 (39%) patients had died, 1013 (83%) of transplant-related causes, 207 (17%) of relapse. 447 (14%) patients had relapsed. The final scoring system was highly predictive for leukaemia-free survival, survival and transplant-related mortality. Survival at 5 years was 72%, 70%, 62%, 48%, 40%, 18%, and 22% for patients with scores 0, 1, 2, 3, 4, 5, and 6, respectively. Risk of transplant-related mortality was 20%, 23%, 31%, 46%, 51%, 71%, and 73%. Data showed the same trends for HLA-identical sibling transplants and unrelated transplants for transplants done in 1989-93 and 1994-96. INTERPRETATION: Pretransplant risk factors are cumulative for individual patients with CML having blood or marrow transplantation. A simple system based on five main factors gives adequate risk assessment for counselling of patients and taking decisions.     

Chromosomal aberrations in lymphocytes predict human cancer: a report from the European Study Group on Cytogenetic Biomarkers and Health (ESCH)

Chromosomal aberrations (CAs), sister chromatid exchanges (SCEs), and micronuclei (MN) in peripheral blood lymphocytes have for decades been used as cytogenetic biomarkers to survey genotoxic risks in the work environment. The conceptual basis for this application has been the idea that increased cytogenetic damage reflects an enhanced cancer risk. Nordic and Italian cohorts have been established to evaluate this hypothesis, and analyses presented previously have shown a positive trend between CA frequency and increased cancer risk. We now report on a pooled analysis of updated data for 3541 subjects examined for CAs, 2703 for SCEs, and 1496 for MN. To standardize for interlaboratory variation, the results for the various cytogenetic end points were trichotomized on the basis of the absolute value distribution within each laboratory as "low" (1-33 percentile), "medium" (34-66 percentile), or "high" (67-100 percentile). In the Nordic cohort, there was an elevated standardized incidence ratio (SMR) for all cancer among subjects with high CA frequency [1.53; 95% confidence interval (CI), 1.13-2.05] but not for those with medium or low CA frequency. In the Italian cohort, a SMR in cancer of 2.01 (95% CI, 1.35-2.89) was obtained for those with a high CA frequency level, whereas the SMRs for those with medium or low did not noticeably differ from unity. Cox's proportional hazards models gave no evidence that the effect of CAs on total cancer incidence/mortality was modified by gender, age at test, or time since test. No association was seen between the SCEs or the MN frequencies and subsequent cancer incidence/mortality. The present study further supports our previous observation on the cancer predictivity of the CA biomarker, which seems to be independent of age at test, gender, and time since test. The risk patterns were similar within each national cohort. This result suggests that the frequency of CAs in peripheral blood lymphocytes is a relevant biomarker for cancer risk in humans, reflecting either early biological effects of genotoxic carcinogens or individual cancer susceptibility.     

Safeguarding the administration of high-dose chemotherapy: a national practice survey by the American Society for Blood and Marrow Transplantation

Overdoses of high-dose chemotherapy before hematopoietic cell transplantation are serious adverse events, but their frequency and etiology are unknown. The American Society for Blood and Marrow Transplantation (ASBMT) conducted an anonymous national survey to identify errors in safety practices during the administration of high-dose chemotherapy. The questionnaire was returned from 115 (68%) of 170 hematopoietic transplant centers in the United States. Ninety-four of the programs were university or affiliated centers, 19 were community hospitals, and 41 were founded since 1990. A total of 7650 transplants were reported for 1994: 22% of the programs performed 1-20 transplants, 60% performed 21-100 transplants, and 18% performed more than 100 transplants. Fifteen of the 115 responding centers reported a total of 18 patients inadvertently given overdoses of cisplatin (n=3), carboplatin (n=2), busulfan (n=2), cytosine arabinoside (n=2), cyclophosphamide (n=2), interleukin-2 (n=2), or other agents (n=5) between 1989 and 1994. Cumulative drug doses given as a daily dose (six cases) and nursing infusion errors (six cases) were the most common errors. The estimated chemotherapy overdose error rate was 0.06%, or 6 cases/10,000 transplants, with 95% confidence limits of 0.03-0.11%. The overdose rate among more experienced centers in operation before 1990 was lower than that among newer centers (p < 0.01). Large centers (> 100 transplants performed in 1994) experienced errors at rates lower than those in medium-sized centers (21-100 transplants, p = 0.03). Although the number of events was small in this self-reporting survey, overdoses were noted in 13% of the responding centers, especially among more recently established units. Safety practices need to emphasize multidisciplinary checkpoints at the physician, pharmacist, nursing, and institutional levels. Based on these survey results, ASBMT recommendations for further safeguards for high-dose chemotherapy administration are proposed.     

A randomized trial comparing busulfan with total body irradiation as conditioning in allogeneic marrow transplant recipients with leukemia: a report from the Nordic Bone Marrow Transplantation Group

Between October 1988 and December 1992, 167 patients with leukemia receiving marrow transplants from HLA-identical donors and conditioned with cyclophosphamide (120 mg/kg) were randomized to additional treatment with either busulfan (16 mg/kg, n = 88) or total body irradiation (TBI; n = 79). The busulfan-treated patients had an increased cumulative incidence of veno-occlusive disease of the liver, ie, 12% compared with 1% in the TBI group (P = .009). Furthermore, hemorrhagic cystitis occurred in 24% of the busulfan patients versus 8% in the TBI patients (P = .003). In patients with advanced disease beyond first remission or first chronic phase, transplantation-related mortality was 62% among the busulfan-treated patients compared with 12% among the TBI recipients (P = .002). These differences between the two groups were statistically significant in multivariate analysis. Seizures were seen in 6% of the busulfan-treated patients and were absent in the TBI group (P = .03). Grade II-IV of acute graft-versus-host disease (GVHD) was similar in the two groups, but grade III-IV and chronic disease was more common in the busulfan-treated group (P = .04). Death associated with GVHD occurred in 17% of the busulfan-treated group and 2% of the TBI group (P = .003). Patients treated with busulfan had a 3-year actuarial survival of 62%, which was worse than the 76% among those treated with TBI (P < .03). In multivariate analysis, poor survival was associated with advanced disease (P < .0001), no posttransplant septicemia (P = .0006), grade II-IV GVHD (P = .006), and busulfan treatment (P < .02). The incidence of relapse did not differ between the two groups. Relapse-free survival was also similar in the two treatment groups on analysis of data from all patients, children, patients with early disease, and those with acute myeloid leukemia, acute lymphoblastic leukemia, and chronic myeloid leukemia. However, in adults (P = .05) and patients with advanced disease (P = .005), leukemia-free survival was significantly better in those treated with TBI. We conclude that patients treated with busulfan have more early toxicity and an increased transplant-related mortality in patients with advanced disease. TBI is therefore the treatment of choice, especially in adults and patients with advanced disease. However, busulfan is an acceptable alternative for patients with early disease and for those in whom TBI is not feasible.     

10 years' neuroblastoma screening in Europe: preliminary results of a clinical and biological review from the Study Group for Evaluation of Neuroblastoma Screening in Europe (SENSE)

Between January 1986 and May 1996, 870,313 children were tested in European neuroblastoma (NB) screening programmes. Among these children, 82 cases of NB (age range 4-24 months, median 11 months) were detected by screening. 83% of the patients had localised NB and 17% were diagnosed with generalised NB (stage 4, 10%; stage 4s, 7%). Unfavourable biological markers (MYCN amplification, loss of heterozygosity (LOH) 1p36, DNA di/tetraploidy) were observed in 14% of 76 biologically examined cases. The median follow-up time of all the patients was 21.5 months (range 1-101 months). To date, 69 patients are in complete remission (CR) and 2 patients have died due to therapy (stage 4, 1 patient; stage 3, 1 patient with unfavourable markers). Apart from screened patients, 16 other patients with NB were found who had previously had a normal screening test, i.e. 'false negative' patients (age range 10-41 months, median 31.5 months). The median interval between screening and diagnosis was 24.5 months (range 6-35 months). 11 of the 'false negative' patients suffered from generalised NB (stage 4) and 5 had localised NB at diagnosis. Unfavourable biological markers were observed in 7/12 patients. 5 patients have died, 2 achieved partial remission and 9 CR. 9 of the 11 patients with unfavourable biological markers diagnosed due to NB screening are currently in CR. It is very likely that, among the patients without unfavourable biological markers, we detected tumours which may have regressed spontaneously. These children may have undergone 'unnecessary,' but unavoidable, diagnostic procedures and therapy. To reduce the number of 'false negative' patients, a later screening could be helpful and should be evaluated.     

Increased incidence of cytomegalovirus (CMV) infection and CMV-associated disease after allogeneic bone marrow transplantation from unrelated donors. The Fukuoka Bone Marrow Transplantation Group

The purpose of this study was to identify correlates of physical activity behavior in a sample of rural, predominantly African American youth. Three hundred sixty-one fifth-grade students from two rural counties in South Carolina (69% African American, median age = 11 years) completed a questionnaire designed to measure beliefs and social influences regarding physical activity, physical activity self-efficacy, perceived physical activity habits of family members and friends, and access to exercise and fitness equipment at home. After school physical activity and television watching were assessed using the Previous Day Physical Activity Recall (PDPAR). Students were classified as physically active according to a moderate physical activity standard: two or more 30-min blocks at an intensity of 3 METs (metabolic equivalents) or greater, and a vigorous physical activity standard: one or more 30-min blocks at an intensity of 6 METs or greater. According to the moderate physical activity standard, 34.9% of students were classified as low-active. Multivariate analysis revealed age, gender, television watching, and exercise equipment at home to be significant correlates of low activity status. According to the vigorous physical activity standard, 32.1% of the students were classified as low-active. Multivariate analysis revealed age, gender, television watching, and self-efficacy with respect to seeking support for physical activity to be significant correlates of low activity status. In summary, gender and the amount of television watching were found to be the most important correlates of physical activity in rural, predominantly African American youth.     

The molecular specificity of action of the tetrapeptide acetyl-N-Ser-Asp-Lys-Pro (AcSDKP) in the control of hematopoietic stem cell proliferation

Nutritional effects have traditionally focused on outcomes, such as nitrogen balance, wound healing, or muscle strength. Little emphasis has been placed on how biochemical or physical improvements translate into functional changes as perceived by the patient. Because glutamine (GLN)-supplemented nutrition promotes protein synthesis and improves nitrogen balance, we assessed the mood of individuals participating in a randomized controlled blinded trial receiving GLN solutions. Patients (n = 23) undergoing marrow transplantation were randomized by the research pharmacist to receive either standard total parenteral nutrition (TPN) (control) or GLN-containing TPN (40 g of glutamine total). The solutions were isocaloric and isonitrogenous and were administered until the patient was eating 50% of estimated requirements. Before TPN and on admission to the hospital, the patient completed the Profile of Mood States questionnaire, a standardized test quantifying the degree of tension, depression, anger, vigor, fatigue, and confusion. The patient completed the questionnaire again at the end of TPN near discharge. The tests were scored and the change from baseline for each mood for both groups of patients was calculated at the completion of TPN. The scores for vigor in the control group (delta scores) decreased over the course of hospitalization as would be expected with a serious illness. The group receiving glutamine TPN, however, essentially showed little change in vigor from baseline and the delta score was significantly different from the control group (delta vigor score -0.85 +/- 2.1 in the glutamine group vs. -5.90 +/- 1.7 in the control group; p = .07).(ABSTRACT TRUNCATED AT 250 WORDS)