We evaluated toxicity, engraftment, chimerism, graft-versus-host disease (GVHD), and response to a dose-reduced allograft after cytoreductive autografting in 17 patients with advanced stage II/III ...multiple myeloma (MM). After autografting with melphalan (200 mg/m2) the patients received after a median interval of 119 days (range 60-210) a dose-reduced regimen consisting of fludarabine (180 mg/m2), melphalan (100 mg/m2), and antithymocyte globulin (3 × 10 mg/kg) followed by allografting from related (n = 7), mismatched related (n = 2), or unrelated (n = 8) donors to induce a graft-versus-myeloma effect. After dose-reduced allografting all patients became neutropenic (< 0.2 × 109/L) for at least 8 days. All patients engrafted with a median time for leukocyte (> 1 × 109/L) and platelet (> 20 × 109/L) counts of 16 (range, 11-24) and 23 days (range, 12-43), respectively. Complete donor chimerism was detected after a median of 30 days (range, 19-38). Acute GVHD stage II occurred in 4 patients (25%) and grade III GVHD in 2 patients (13%). Chronic GVHD developed in 40% of the patients, but only 1 patient experienced extensive chronic GVHD requiring further immunosuppressive therapy. Two patients died of alveolar hemorrhage and pneumonia, resulting in a day 100 mortality rate of 11%. The rate of complete remission with negative immunofixation increased from 18% after autografting to 73% after allografting. After a median follow-up of 17 months after autologous and 13 months after allogeneic transplantation 13 patients are alive and 12 of them free of relapse or progression. The tandem auto-allotransplant protocol is highly active and provides rapid engraftment with complete donor chimerism and tolerable toxicity.
Objective
To test the effects of the use of a collapsible, portable chair (chair B), as opposed to a ‘standard’ chair (chair A), on the outcome of the timed “Up and Go” (TUG) test.
Design
...Cross-sectional.
Setting
Multipurpose senior centres.
Participants
Mobile older persons (N= 118, mean age 77 years (range 62–99 years)).
Outcome measures
Time to complete the timed “Up and Go” test using chair A and chair B, and inter-rater agreement in the time scores.
Results
Time taken to complete the TUG test did not differ by chair type median (interquartile range, IQR) = 12.3 (9.53–15.9) and 12.6 (9.7–16.6) seconds for Chair A and B respectively, p-value=0.87. In multiple regression analyses, factors that impacted on time difference in test performance for the two chairs were use of a walking aid during the test Odds ratio (OR) = 3.7 95%CI 1.1–11.9, p=0.031, observed difficulty with mobility (OR= 27.7 95%CI 2.6–290, p=0.006), and a history of arthritis in the knees (OR= 2.9 95%CI 1.0–8.7, P=0.05). In an inter-rater agreement analysis, no significant difference was found between time scores recorded by the two raters; median (IQR) = 12.4 (10.9–15.9) and 12.3 (7.2–59.1) seconds for the occupation therapist and for the research assistant, respectively (Wilcoxon matched pairs test, p=0.124, Spearman correlation coefficient = 0.99, p<0.001).
Conclusion
The use of a portable canvas chair with standardised specifications offers an acceptable alternative to the use of a ‘standard’ chair in assessments of fall risk using the TUG test in field settings where field workers are reliant on public transport.
The study investigated in detail neutrophil functions shortly after allogeneic peripheral blood stem cell transplantation (PBSCT).
Different functions of neutrophils in 14 patients who received ...allogeneic PBSCT were investigated. The migratory capacity as well as the ability to induce oxidative burst following stimulation with either Phorbol-12-myristate-13-acetate (PMA), the chemotactic peptide N-formyl-Met-Leu-Phe (f-MLP) or opsonized Escherichia coli was analysed after engraftment (between day +30 and +40) and compared with the results obtained from healthy volunteers.
There are no differences in terms of the migratory capacity (P = 0.17), as well as regarding the oxidative burst after incubation with PMA (P = 0.08) or f-MLP (P = 0.06), compared with healthy men. In contrast, the capacity of neutrophils to induce oxidative burst following stimulation with E. coli is highly impaired (P = 0.0001) in patients shortly after engraftment.
The recovery of neutrophils after allogeneic PBSCT is not only influenced by the varying time of engraftment, but also represents a process that differs in distinct biological functions compared to normal granulopoieses.
In this open single-centre phase II study, MMF was added on day +10 after allogeneic transplantation to standard immunosuppressive prophylaxis consisting of cyclosporine and methotrexate to decrease ...the incidence of GvHD. In all, 30 patients aged 20-59 years with advanced haematological malignancies received an unmanipulated blood-stem-cell graft (median of 8.5 x 10(6) CD34(+) and 349 x 10(6) CD3(+) cells per bodyweight) from matched unrelated (n=26), or mismatched donors (n=4). Prior to transplantation, 13 patients underwent fractionated total body irradiation and cyclophosphamide, one patient additional etoposide. In all, 16 patients received reduced conditioning of fludarabin, busulfan, and antithymocyte globulin. All patients engrafted in a median of 12 days, and 19 developed acute GvHD>/=II, including two patients with GvHD III and three with GvHD IV. Subsequently, nine patients developed limited and two patients extensive chronic GvHD. With a median follow-up of 28 months, the overall survival is 53.3% and disease-free survival 50%, respectively. Only two deaths were due to GvHD IV. Out of 13 patients, 10 being CMV IgG positive became positive for pp65. In conclusion, this MMF schedule seems to be safe and feasible in the prophylaxis of severe acute GvHD for high-risk patients, restricted by an increased risk for reactivating CMV in seropositive patients.
This study was undertaken to evaluate the hypothesis that treatment with granulocyte colony–stimulating factor (G-CSF) to mobilize bone marrow cells (BMCs) is feasible and safe and promotes ...neovascularization and myocardial function in patients with acute myocardial infarction.
Fourteen patients in the treatment group and 9 patients in the control group were enrolled in this prospective, nonrandomized, open-label study. Forty-eight hours after successful recanalization and stent implantation, the patients of the treatment group received 10 μg/kg body weight per day G-CSF subcutaneously for mean treatment duration of 7.0 ± 1.0 days. Nine patients fulfilled the entry criteria but refused participation and served therefore as control group. In both groups, regional wall motion and perfusion was evaluated with electrocardiogram-gated sestamibi single-photon emission computed tomography imaging and ejection fraction with radionuclidventriculography before discharge and after 3 months.
No severe side effects of G-CSF treatment were observed. There was a significant improvement of the regional wall motion and perfusion within the treatment group (
P < .0001) and between the treatment and control group (
P < .05 and
P < .01, respectively). Ejection fraction in the treatment group increased from 0.40 ± 0.11 to 0.48 ± 0.13 (
P < .01), whereas in the control group, ejection fraction increased from 0.40 ± 0.13 to 0.43 ± 0.13 (
P = .049). A control angiography of the treatment group after 12.4 ± 6.6 months showed an in-stent restenosis in 1 patient.
In patients with acute myocardial infarction, treatment with G-CSF to mobilize BMCs is feasible and safe and seems to be effective under clinical conditions. The therapeutic effect might be attributed to BMC-associated promotion of myocardial regeneration and neovascularization.
Experimental and preliminary clinical data suggest that transplantation of autologous bone marrow cells (BMC) may contribute to regeneration of the myocardium after acute myocardial infarction. This ...approach should be tested in patients with large infarctions in whom a positive effect would be most beneficial.
After successful recanalization within 5.9±2.5 h and stent implantation in five patients with a large acute anterior myocardial infarction (AMI), the patients received autologous mononuclear BMCs via a balloon catheter placed into the left anterior descending artery 6.3±0.4 days after revascularization. At 3-month follow-up, no improvement was observed for left ventricular ejection fraction, regional wall motion in the infarcted zone, contractility index measured via dobutamine stress echocardiography, coronary blood flow reserve and maximal oxygen uptake, respectively. After further follow-up of 12 months, again no change of the left ventricular ejection fraction could be detected.
Intracoronary transplantation of autologous mononuclear BMCs did not improve cardiac function in our patients with large anterior myocardial infarctions after 3 and 12 months.
Bendamustine is an alkylator with anticipated antimetabolic activity. It has shown activity in malignant lymphoma, multiple myeloma, and breast cancer. Recognized side-effects are relatively mild ...with myelosuppression as the dose-limiting toxicity. The CD4/CD8 ratio may be reduced. To what extent the alteration of lymphocytes, especially CD4(+) lymphocytes, correlates with an increase in opportunistic infections cannot be definitively answered.
The patient, female, aged 48 years, was suffering from an advanced progressive breast cancer. After initial treatment with several chemotherapies, a cytotoxic therapy was initiated, with bendamustine (150 mg/m(2)) administered on two consecutive days and repeated every 4 weeks. After five courses, the patient developed Pneumocystis carinii pneumonia (PCP), disclosed in the bronchoalveolar lavage. While receiving bendamustine therapy, the CD4(+) and CD8(+) lymphocyte counts in the peripheral blood were determined by flow cytometry. The next-to-normal CD4/CD8 ratio before therapy (0,82) had decreased to 0,05 during the therapy mainly due to a decline of CD4(+) lymphocyte. The patient was seronegative for human immunodeficiency virus. In spite of high-dose intravenous trimethoprim/sulfamethoxazole and methylprednisolone application, the patient died of a respiratory failure 3 days after PCP was diagnosed.
Bendamustine is capable of inducing a reduction in CD4(+) lymphocyte counts causing a severe T-lymphocyte-mediated immunosuppression. Measuring CD4(+) lymphocyte counts may be helpful in determining the risk of PCP in patients treated with bendamustine.
Summary
Legionnaires’ disease is an acute bacterial infection, generally caused by Legionella pneumophila, which primarily involves the lower respiratory tract, although it is often associated with ...multisystemic extrapulmonary features. Cutaneous features are very uncommon and may include erythematous or petechial, macular or maculopapular lesions. We report a male patient who expressed all features of a severe lobular pneumonia. Over the course of the disease the patient developed a livid erythematous, maculopapular exanthem rapidly extending over the entire body. Given the rapid development and target‐like appearance of the skin lesions with extensive skin involvement and blister formation, the initial diagnosis was that of a severe cutaneous drug reaction. However, histological examination of biopsy did not confirm this diagnosis, but instead was suspicious for a viral exanthem or a more aggressive inflammatory response due to sensitization to bacterial antigens. L. pneumophila infection was verified during the course of the disease.
An extractive industries boom in Africa is driving unprecedented expansion of infrastructure into sparsely populated regions. Much of the investment is in high-volume minerals such as iron and coal ...that will require heavy infrastructure and large settled workforces. New roads and railways are being built to support these industries. Mineral infrastructure is reinforcing the dynamic of designated “growth corridors”, which are increasingly determining settlement patterns and rural land use in Africa. These corridors are penetrating into areas where agriculture has been constrained by lack of access to markets. They could unleash a major expansion of arable crops in the Guinea and Miombo savannahs, tropical tree crops in Congo Basin rainforests and irrigated agriculture on the floodplains of several African river systems. Rapidly growing African cities are largely dependent on imported food but growth corridors linking them to hinterland areas could favour shifts to African-sourced foods. Governance weaknesses may allow outside investors to make land grabs along growth corridors and further marginalise poor smallholders. New pressures on environmentally sensitive areas may emerge. Policy changes are needed to avoid negative impacts of this major new development trend and to exploit the potential for poverty alleviation and food-security benefits.
•Impact of mineral industries on agricultural development patterns in Africa.•An unprecedented expansion of mining infrastructure is going to open up many remote areas in Africa to modern agriculture.•A more prosperous population and improved access to markets will create new opportunities for farmers to intensify their production.•Poverty alleviation and food security may improve but governance weaknesses may allow outside investors to make land grabs and further marginalise poor smallholders.
Recombinant human granulocyte colony-stimulating factor (rhG-CSF) mobilized peripheral blood progenitor cells (PBPCs) from healthy individuals are a rapidly emerging alternative source to bone marrow ...for allogeneic transplantation. Although widely applied in the meantime, only limited information on feasibility and safety of mobilization and collection of PBPCs is currently available from prospective multicenter studies specifically designed to investigate this donation modality. This ongoing multicenter study on the performance as well as the short- and long-term safety profile of rhG-CSF-induced mobilization and collection of PBPCs was initiated in October 1999. The study is designed to recruit a total of 300 healthy family donors who will be followed regularly for a period of 5 years after donation. The first interim report presented here summarizes results obtained after enrollment of 150 donors from nine German institutions. The study protocol allowed the individual choice between two dose regimens of rh-CSF (10 micro g/kg per day vs 2x8 micro g/kg per day of donor body weight). The primary endpoint was defined as a yield of > or =5x10(6) CD34(+) cells/kg of recipient body weight in a single leukapheresis product. This endpoint was attained by 50% of donors receiving the lower rhG-CSF dose regimen and by 75% of donors with the higher dose regimen ( p<0.0009). A total of 478 acute adverse events attributable to the mobilization procedure were recorded and manifested predominantly as transient bone pain and headaches (80%). No persistent hematologic or nonhematologic adverse events have occurred in this study so far. Thus, the current experience in a prospective multicenter study supports previous single-center and retrospective registry reports in that the collection of PBPCs after rhG-CSF mobilization is feasible and associated with frequent, but generally mild and acceptable side effects.
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