Validity of the single-particle approach for electron transport in quantum wires assisted by surface acoustic waves.

We study by means of time-dependent numerical simulations the quantum entanglement stemming from the Coulomb interaction between two electrons trapped in the minima of the piezoelectric potential generated by surface acoustic waves. We find that for particles captured in low-energy bound states the quantum correlations turn out to be negligible, thus validating a single-particle approach to the dynamics of such systems. At long times, for high-energy electrons, a substantial entanglement appears, which is an indicator of a mostly correlated dynamics.

There exist nonorthogonal quantum measurements that are perfectly repeatable.

We show that, contrary to the widespread belief, in quantum mechanics repeatable measurements are not necessarily described by orthogonal projectors--the customary paradigm of observable. Nonorthogonal repeatability, however, occurs only for infinite dimensions. We also show that, when a nonorthogonal repeatable measurement is performed, the measured system retains some "memory" of the number of times that the measurement has been performed.

Immunomodulating effects of extracorporeal photochemotherapy in rat experimental allergic encephalomyelitis.

Experimental allergic encephalomyelitis (EAE) is a well-established model of human multiple sclerosis that is commonly used to evaluate the possible effectiveness of new treatments in this disease. Extracorporeal photochemotherapy (ECP) is an immunomodulating procedure currently used in several non-neurological diseases that, like multiple sclerosis, are likely to be due to T-cell-mediated autoimmunity. In this study we examined the effect of ECP using the EAE paradigm in the Lewis rat. In our model, ECP induced a significant modulation in peripheral blood T-cell distribution, changes which are typical of EAE. Remarkably, this effect was closely correlated with the clinical and pathological results, which showed reduced severity of the disease in the ECP-treated EAE animals vs. the EAE alone rats. We conclude that ECP induces modifications in the immunological events that occur during the course of EAE in rats, thus giving support to the hypothesis that it could be used in the treatment of multiple sclerosis.

Purified autologous grafting in childhood acute lymphoblastic leukemia in second remission: evidence for long-term clinical and molecular remissions.

Autologous transplantation is a treatment option for relapsed childhood acute lymphoblastic leukemia (ALL) in second complete remission (CR2) when a suitable donor is not available. In an attempt to prevent relapses originating from graft leukemic contamination, the experimental protocol of in vitro purification of leukapheretic products with monoclonal antibodies (MoAbs), previously reported for adults, was adopted in 11 of 12 consecutive patients (median age, 9 years) with B cell precursor ALL in CR2 after late relapse (median, 37; range, 31-51 months after the onset) enrolled between July 1997 and July 1999 at a single pediatric center. At a median of 12 days after the mobilizing chemotherapy followed by G-CSF, a median of 13.9 (range, 5.9-18.7) x 10(6) CD34+ cells/kg were collected from each patient and a median of 7.5 (range, 4.1-12.6) x 10(6) CD34+ cells/kg underwent the purification procedure. The first step of immunorosetting allowed a one-log reduction of the total cell count, by eliminating more than 90% of the CD11b+ cells; the second step, performed after incubation with anti-CD19 MoAbs, allowed the depletion of 99% (range, 93-100) of the CD19+ cells, kept within the magnetic field of the immunodepletion column, with a median recovery of 73% (range, 55-87) of the collected CD34+ cells. Molecular analysis assessed the in vitro eradication of detectable leukemic cells. A median reinfusion of 5.2 (range, 3.2-9.1) x 10(6) CD34+ cells/kg for each patient (median viability, 90%), after conditioning with the 'TBI-VP16-CY' regimen, allowed prompt engraftment and immunological reconstitution; no patients experienced severe transplant-related toxicity or major infections. One patient relapsed 7 months after transplantation, while 10 patients are alive in clinical and molecular remission, at a median follow-up of 29 months (range, 15-40) (2-year EFS, 89%, s.e. 9). In conclusion, the procedure proved to be reproducible for pediatric purified autografting, highly efficient concerning stem cell recovery and depletion of leukemia-lineage specific cells, and promising in terms of final outcome.

Electrolyte monitoring in patients undergoing peripheral blood stem cell collection.

In recent years peripheral blood stem cell (PBSC) collection for allogeneic or autologous transplantation has experienced an increased use in the onco-hematological setting. The latest generation cell separators allow a satisfactory and safe PBSC collection. Nevertheless, as in all therapeutic apheresis procedures, patients may experience procedure-related side-effects, mainly vasovagal reactions or symptoms related to hypocalcemia and/or hypomagnesemia. We investigated electrolyte changes in 18 patients, with a median age of 46 years (range 7-62), undergoing PBSC collection from January to April 1998. A significant decrease in total calcium in the final sample (9.65 +/- 0.7 mg/dL) with respect to the basal one (9.2 +/- 0.6 mg/dL, P < 0.05) was observed; also ionized calcium decreased markedly from the first sample drawn at +30 minutes: 1.22 +/- 0.14 vs. 1.03 +/- 0.15 mmol/L (P < 0.05), and a highly significant difference emerged when basal value were compared to the final value: 1.22 +/- 0.14 vs. 0.94 +/- 0.13 mmol/L (P < 0.0001). Similar findings affected potassium concentration: 4.1 +/- 0.4 vs. 3.3 +/- 0.3 mEq/L (P < 0.0001). Three out of eighteen patients (16.7%) reached a final potassium level <3.0 mEq/L, and eight out of eighteen (44.5%) showed a potassium concentration decrease >20% with respect to the basal value. A mild metabolic alkalosis occurred during the procedure: pH increased from 7.35 +/- 0.02 to 7.43 +/- 0.028 (P < 0.001), and plasma bicarbonate concentration increased from 27.48 +/- 2.21 to 32.44 +/- 2.52 mmol/L (P < 0.01). Sodium and chloride did not differ in the final sample with respect to the basal sample. None of our patients experienced clinically relevant side effects related to severe electrolyte changes (i.e., >20% with respect to the basal value). Because our current therapeutic schedules include patients older than 50 years in the PBSC collection and transplantation program and since it is well known that subclinical myocardial disease may occur in up to 4% of middle-aged males, we suggest that patients aged 50 or older undergoing PBSC collection procedures be carefully monitored in order to identify significant electrolyte variation, especially if they present with low serum potassium levels. However, further investigation of larger patient series are needed to determine the clinical relevance of serum potassium changes during apheresis.

Evidence of induced non-tolerance in HLA-identical twins with hemoglobinopathy after in utero fetal transplantation.

Fetus-to-fetus transplantation has been suggested for the treatment of hemoglobinopathies in utero. However, dissimilar results have to date been obtained by different groups. We describe a case in which fetus-to-fetus transplantation in HLA-identical twins was performed at the 19th week of gestation by infusion of 0.8 ml of fetal blood from normal to beta-thalassemia affected fetus with the main aim of inducing tolerance. No evidence of engraftment, determined by KM19 polymorphism, was present after 2 years of the procedure. Moreover, an alloreactive cytotoxic T lymphocyte precursor (CTLp) study of affected fetus vs donor and other different stimulators showed that immunization vs tolerance was the real effect of the procedure.

Treatment of normal donors with rhG-CSF 16 micrograms/kg for mobilization of peripheral blood stem cells and their apheretic collection for allogeneic transplantation.

BACKGROUND: Utilization of peripheral blood stem cells (PBSC) in allogeneic transplantation requires a method for their mobilization and collection that is not inconvenient for the donor. METHODS: We administered rhG-CSF (filgrastim) 16 micrograms/kg subcutaneously for 4 days in five normal subjects (age 18-31, M = 3, F = 2), previously selected as HLA-identical donors of siblings with leukemia. All the donors gave written informed consent. On days 4 and 5 (in one donor on day 6 too), 10:l leukapheretic collection was performed with a CS-3000 (Baxter) or an AS-104 (Fresenius) cell separator through the antecubital vein. RESULTS: The WBC count reached a median peak of 57.0 x 10(9)/L on day 5. The peripheral blood CFU-GM peaked to a median level of 8908/mL on day 5 with a median increase over baseline values of 39.1 times. The CD34+ cells peaked to (median) 147.0 x 10(6)/L on day 4 with a median increase of 65.3 times. A lesser enrichment was recorded for BFU-E (median increase 12.7 times) and CFU-GEMM (median increase 15.2 times). Even CD3+ and CD56+CD3- cells increased (median 1.7 and 1.5 times, respectively). A median of 771 x 10(8) MNC (range 672-1378), 116.4 x 10(6) CFU-GM (range 47.7-145.1) and 754 x 10(6) CD34+ cells (range 477-2599) were apheretically collected. Concerning side effects, mild to moderate back pain and general minor discomfort were reported by all donors. The platelet level regularly but transiently decreased after completion of the apheretic procedures with a median nadir of 69 x 10(9)/L (range 43-126) on (median) day 7, but in no case did thrombocytopenia cause bleeding. The thrombocytopenia was more pronounced with the CS-3000 than the AS-104 apparatus. CONCLUSIONS: rhG-CSF 16 micrograms/kg x 4 days is an efficient schedule for PBSC mobilization in healthy donors, but lower doses and even a single apheresis procedure might prove similarly adequate.

Engraftment kinetics and long-term stability of hematopoiesis following autografting of peripheral blood stem cells.

BACKGROUND: We analyzed short-term and sustained hematopoietic reconstitution after high-dose therapy with peripheral blood stem cell (PBSC) support in patients with various malignant disorders. METHODS: Fifty-six patients, all with malignant hematologic disorders, were autografted between 1989 and 1994 using PBSC (47 pts) or PBSC + bone marrow (BM) cells (9 pts). PBSC were collected after mobilization with chemotherapy +/- hematopoietic growth factors (GF). RESULTS: All patients engrafted > 0.5 x 10(9)/L polymorphonuclear cells (PMN) and > 50.0 x 10(9)/L Plt at a median of 12 (8-32) and 13 (9-365) days, respectively. Thirty-nine patients were evaluable for long-term graft performance, and their hematologic values at 30 and 100 days, at 6 months and at 1, 2, 3, 4 and 5 years were retrospectively analyzed. Steady counts were recorded over the years. None of the patients had late graft failure. CONCLUSIONS: PBSC given after high-dose chemotherapy ensure a fast hematologic recovery with stable graft performance up to five years after autograft. Though this is not definitive proof of the presence of uncommitted stem cells in the PBSC population, it gives further support to the idea that PBSC are as safe as bone marrow for long-term engraftment. A delayed or incomplete recovery of platelets may occur with low PBSC counts or when disease relapse occurs rapidly after autograft.

Mobilization of circulating progenitor cells in multiple myeloma during VCAD therapy with or without rhG-CSF.

BACKGROUND: Circulating progenitor cells (CPC), when infused in large numbers, rapidly repopulate the marrow after myeloablation with high-dose therapy. In multiple myeloma (MM), as in other disorders, different chemotherapy regimens, including single-as well as multiple-agent chemotherapy, with or without hemopoietic growth factors, have been proposed to mobilize these progenitor cells into the blood. Here we report our experience with a drug combination called VCAD and compare the results to those obtained by adding rhG-CSF to the same combination. METHODS: Fourteen MM patients were given one course of VCAD, a chemotherapy association of vincristine 2 mg, cyclophosphamide 4 x 0.5 g/m2, adriamycin 2 x 50 mg/m2 and dexamethasone 4 x 40 mg, before undergoing apheresis to collect CPC for autografting. Seven also received rhG-CSF (filgrastim) 5 mcg/kg/day over the period of apheresis. These latter were allocated to rhG-CSF treatment sequentially from the time the drug became available for clinical use. RESULTS: Following VCAD-induced pancytopenia, CFU-GM peaked at a median of 853/mL (range 96-4352; 7.6 times basal level). RhG-CSF administration increased CFU-GM levels but not significantly. With rhG-CSF the CFU-GM peak was reached sooner, toxicity was reduced and granulocytopenia less protracted. Fewer aphereses were run in the rhG-CSF group, there were higher yields per single run, and patients began and completed their collection program more quickly. CONCLUSIONS: The VCAD association is able to mobilize CPC in patients with MM, and rhG-CSF is recommended as a fundamental part of the priming schedule.

Cyclophosphamide 4 g/m2 plus rhG-CSF for mobilization of circulating progenitor cells in malignant lymphomas.

We report the preliminary results of a study exploring the possibility of collecting circulating progenitor cells (PBSC) with a protocol based on the administration of single doses (4 g/m2) of cyclophosphamide and G-CSF (5 or 10-micrograms/kg) in 9 patients with non Hodgkin's lymphoma. The peak level of CD34+ cells occurred after a median of 10 days (range 8-11), generally coinciding with the median peak level of CFU-GM, with a mean 31.27 fold increase above basal levels. 3 (range 2-5) leukaphereses were required to harvest a median number of 25.1 x 10(4)/kg (8-105) CFU-GM and of 9.4 x 10(6)/kg (1.2-25) CD34+ cells. No difference was recorded between 5 and 10 micrograms/kg of G-CSF in terms of PBSC yield. In transplanted patients, a strong correlation was found between CD34+ cells infused/kg and platelet recovery (r = -0.8, p = 0.002). No toxicity was observed and apheretic procedures were regularly performed outpatiently. Our conclusion is that this protocol is particularly suitable for an outpatient treatment/collection program.

ANLL patients with normal karyotype are not a homogeneous prognostic group.

BACKGROUND AND METHODS: Karyotype in ANLL is referred as an independent prognostic factor. The prognosis of diploid ANLL subjects has been defined as "good" by some authors, or, more recently, "intermediate" by others. This is a retrospective study on 30 consecutive heavy treated ANLL diploid patients with the aim to make a correlation among age, normal karyotype and response. Chromosomal banding studies were performed at presentation with GTG technique. Diploid patients were divided into two age groups < 60 years (17 cases) and > or = 60 (13 cases). Data were analyzed by NCSS software. RESULTS AND CONCLUSIONS: CR rate for the two diploid age groups was 94% and 38% respectively (p = 0.002). Median DFS and overall survival were 14.4 and 23.3 months, 4 and 5 months for the two subgroups respectively: these data were not statistically significative. The probability of achieving CR was not affected by blood counts and Karnofsky performance status on admission, but only by age. Though ANLL patients with the same karyotype have the same course regardless of other prognostic factors, this does not occur in our series of diploid patients. We suggest that a normal karyotype, at least as defined with the GTG technique, does not characterize a homogeneous group of patient. Heterogeneity in this group might be due to submicroscopic or molecular genetic changes; it can enhance the age as prognostic factor.