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Spontaneous neoclassical tearing modes (spontaneous NTMs) have been observed in the National Spherical Torus Experiment (NSTX). Recently, a TRANSP based model for the modified Rutherford equation analysis was developed to accurately predict the effect of fast ions on the growth of magnetic islands. The goal of this paper is to utilize the TRANSP NTM model to understand the role of fast ions in NSTX spontaneous NTMs. Our analysis shows that when the passing fast ion driven kinetic neoclassical polarization current term is larger than 1% of the bootstrap current term in the modified Rutherford equation, fast ions play a decisive role in the early growth phase of spontaneous NTM. This result is applicable to any tokamak plasmas with a fast ion drift orbit width, or the fast ion poloidal Larmor radius, comparable to the magnetic island width.

This presentation examines the energetic particle transport induced by saturated kink modes and sawtooth crashes in JET deuterium plasmas. It is known that kink mode-resonant transport and phase-space redistribution from sawtooth crashes can drive strong fast ion transport with dependencies on particle pitch and energy. Measurements with JET’s Faraday cup fast ion loss detector array have shown that the internal kink growth phase preceding sawtooth crashes produces substantial fast ion losses. This report will numerically investigate the dominant energetic particle transport mechanism with a detailed examination of the fast ion phase-space dependencies, resonances, orbit topology changes, induced losses, and redistribution associated with the long-lived, resonant, kink mode and non-resonant sawtooth crash. The ORBIT-kick model forms the basis of the transport studies with realistic fast ion distributions produced from TRANSP. A recently created reduced model for sawtooth induced transport is used while the saturated kink modes are modeled with ideal magnetohydrodynamic codes. The simulations were further validated against experiment with a newly developed synthetic Faraday cup fast ion loss detector in addition to scintillator probe and neutron measurements.

The performance of fusion devices relies strongly on the good confinement of energetic particles (EPs). Therefore, the investigation of EP transport by magnetohydrodynamic instabilities is one of the key aspects in the development of plasma scenarios. Alfvénic instabilities in particular can lead to significant losses of alpha particles that are essential for plasma self-heating. A so-called afterglow scheme has been developed to study the destabilization of Alfvén eigenmodes (AEs) by alpha particles and associated EP transport in the JET tokamak. In this work, the linear stability of AEs is discussed for the partial afterglow phase in a JET deuterium plasma discharge and for the full afterglow phase in a projected deuterium–tritium (DT) plasma. Thanks to recent upgrades in the tokamak transport code TRANSP, one can account for the contributions of different EP species to mode stability. Analysis of deuterium plasmas shows that AE growth rates are extremely sensitive to the energy and distribution of fast ions. An increase in fast ion energy can lead to more unstable AEs. In the afterglow phase of projected DT plasmas, it is EPs that mostly drive the AEs. However, the drive by alpha particles is comparable to that by beam ions and their contribution to the net growth rate might be hard to separate. According to the discussed projections, the destabilization of AEs might be ineffective because the background plasma damping significantly exceeds the EP drive. In this case, the development of an alternative plasma scenario that allows us to overcome such damping would be required in future experiments.

Alfvénic instabilities (AEs) are well known to cause enhanced transport of energetic particles (EPs) in fusion devices. Most studies until now have focused on characterizing and understanding AE stability in single-species plasmas heated by neutral beams (NB), where deuterium is typically used as both main plasma species and NB fuel. As the fusion community moves toward fusion reactors that target burning plasma conditions, such as ITER, the single-species picture breaks down. Burning plasmas, which will use a mix of deuterium and tritium (DT) as main fuel, also feature the presence of several supra-thermal fusion products such as alpha particles, protons, helium isotopes and high-energy tritium ions. This work presents the extension of the EP transport kick model implemented in the TRANSP time-dependent tokamak transport code to study the combined effect of multiple EP species on AE stability and, in turn, the response of different EP species to plasma instabilities in terms of their redistribution and losses. Further validation of the enhanced model is planned based on experimental results expected from the JET DT campaign scheduled for 2021, in preparation for ITER plasmas and beyond.

In this paper, we report the novel experimental observation of both unstable and stable toroidicity-induced Alfvén eigenmodes (TAEs) measured simultaneously in a JET tokamak plasma. The three-ion-heating scheme (D-DNBI-3He) is employed to accelerate deuterons to MeV energies, thereby destabilizing TAEs with toroidal mode numbers n = 3–5, each decreasing in mode amplitude. At the same time, the Alfvén eigenmode active diagnostic resonantly excites a stable n = 6 TAE with total normalized damping rate −γ/ω 0 ≈ 1%–4%. Hybrid kinetic-MHD modeling with codes NOVA-K and MEGA both find eigenmodes with similar frequencies, mode structures, and radial locations as in experiment. NOVA-K demonstrates good agreement with the n = 3, 4, and 6 TAEs, matching the damping rate of the n = 6 mode within uncertainties and identifying radiative damping as the dominant contribution. Improved agreement is found with MEGA for all modes: the unstable n = 3–5 and stable n = 2, 6 modes, with the latter two stabilized by higher intrinsic damping and lower fast ion drive, respectively. While some discrepancies remain to be resolved, this unique validation effort gives us confidence in TAE stability predictions for future fusion devices.

The growth of magnetic islands in NSTX is modeled successfully, with the consideration of passing fast ions. It is shown that a good quantitative agreement between simulation and experimental measurement can be achieved when the uncompensated cross-field current induced by passing fast ions is included in the island growth model. The fast ion parameters, along with other equilibrium parameters, are obtained self-consistently using the TRANSP code with the assumptions of the ‘kick’ model (Podestà et al 2017 Plasma Phys. Control. Fusion 59 095008). The results show that fast ions can contribute to overcoming the stabilizing effect of polarization current for magnetic island growth.

An integrated energetic particle transport model has been constructed in JET plasmas constrained by experimental fast ion loss measurements. The model incorporates a synthetic fast ion loss detector identical to JET’s thin-foil Faraday cup fast ion loss detector array. The loss model combines analyses from the TRANSP and ORBIT-kick codes with enhanced features for producing the synthetic diagnostic. Extensions to the ORBIT code framework allow a full-orbit representation within the vacuum region that can map particles directly to an installed detector geometry. Since synthetic fast ion loss detectors are plagued by weak loss statistics, a novel reverse integration biasing scheme has been implemented to boost computational efficiency. The model is validated against experimental loss measurements induced by long-lived kink modes and is found to be in good agreement. This confirms the development of a fully integrated transport/loss model which can be quantitatively verified against experiment allowing for future validation and predictive studies. The model is particularly useful for more complicated plasma scenarios that involve multiple fast ion species such as JET’s 2021 DT-campaign.

On the Recommended Vernacular Names of Mesoplodon peruvianus Reyes, Mead & Van Waerebeek, 1991 (Cetacea, Ziphiidae) in Several World Languages Relevant and distinctive vernacular species names are essential to assure efficient communication among scientists under field and laboratory conditions, but also among non-specialists including the public at large. We provide a rationale for recommended vernacular and alternative names for the lesser beaked whale Mesoplodon peruvianus Reyes, Mead & Van Waerebeek, 1991 in 11 major world languages which encompass most of cetacean literature. Principal criteria for name endorsement are unambiguity and nonrepetitiveness with respect to other aquatic mammal species.

This paper provides a summary of 25 years of research on Risso's dolphins (Grampus griseus) in the western Ligurian Sea. Seasonal variations in abundance, distribution and habitat use were observed. Photographic mark-recapture methods provided a population size estimate for the period from 1998 to 2012, of about 100 individuals (95% CI of 60-220 individuals). The same methods detected a decline in population size from an average of about 120-150 from 2000 to 2005, to an average of 70-100 during 2010 to 2014. Species occurrence appeared to be significantly decreasing in coastal and continental slope areas, while it seemed to be stable in the most pelagic area. In addition, a dramatic change was observed in the local primary production, which was analysed based on time series of sea surface temperature and chlorophyll data from 1990 to 2014. Based on fisheries landings, there may have been a general decrease in fishery productivity, both in the western Ligurian Sea and in adjacent regions. Environmental variability, depletion of resources by fisheries and possibly interspecies competition may all have contributed to cause changes in Risso's dolphin habitat use and occurrence in the western Ligurian Sea.

Cuvier's beaked whale (Ziphius cavirostris G. Cuvier, 1823) is the only beaked whale species commonly found in the Mediterranean Sea. Until recently, species presence in this area was only inferred from stranding events. Dedicated cetacean surveys have increased our knowledge of the distribution of Cuvier's beaked whales, even though many areas still remain unexplored. Here, we present an updated analysis of available sighting and stranding data, focusing on the atypical mass strandings that have occurred in the Mediterranean Sea since 1963. We describe in detail the five more recent events (2006-14), highlighting their relationship with naval exercises that used mid-frequency active sonar. The distribution of the species is apparently characterized by areas of high density where animals seem to be relatively abundant, including the Alborán Sea, Ligurian Sea, Central Tyrrhenian Sea, southern Adriatic Sea and the Hellenic Trench, but other such areas may exist where little or no survey work has been conducted. Population size has been estimated for the Alborán and Ligurian seas. Habitat modelling studies for those areas, confirmed the species preference for the continental slope and its particular association with submarine canyons, as has also been found to be the case in other areas of the world. The application of results from habitat modelling to areas different from their calibration sites is proposed as a management tool for minimizing the potential impacts of human activities at sea. Military sonar is known worldwide as a threat for this species and is suggested to be a major threat for Cuvier's beaked whale in the Mediterranean Sea.

We report herein the results of post-mortem, parasitological, microbiological, histopathological, immunohistochemical (IHC), indirect immunofluorescence (IIF), biomolecular (RT-PCR) and serological investigations carried out on 8 (1 male calf, 1 subadult female, 5 adult females, 1 adult male) striped dolphins (S. coeruleoalba) found stranded from August to November 2007 on the Ligurian Sea coast of Italy. A (broncho-interstitial) pneumonia occurred in 6 animals, with numerous parasitic bodies in both pulmonary and extra-pulmonary locations. Histologically, a multifocal, subacute to chronic, nonpurulent meningo-encephalitis occurred in 1 adult male and 3 adult females, with more or less prominent perivascular cuffs of inflammatory mononuclear cells and peri-paravascular macrophage accumulations. A mild choroid plexus lymphocytic-plasmacytic infiltration was also present, along with moderate neuronal damage, although no viral inclusions were seen in any brain cell (nor in any other cell type). The blood sera from 4 dolphins (1 calf, 1 subadult, 2 adults) had anti-Morbillivirus neutralizing antibodies, with positive titres ranging from 1:10 to 1:40. Nevertheless, IHC, IIF and RT-PCR investigations gave negative results in all animals. On the basis of the above findings, we conclude that one or more factors other than Morbillivirus likely were the primary cause of these dolphin mortality episodes.

Aim: Despite its enormous relevance, homing of hematopoietic stem cells (SCs) remains relatively uncertain due to the limitations of measuring small number of systemically administered cells in the different organs. Despite its high sensitivity, radionuclide detection has been relatively underutilized to this purpose since it cannot differentiate hematopietic SCs recruited by target tissues from those circulating in the blood pool. Our study aims to verify the potential of tracer kinetic approaches in estimating the recruitment of labeled SCs after their systemic administration. Methods: Twenty-four Lewis rats underwent administration of 2 millions cells labeled with 37 MBq of 99mTc-exametazime. Animals were divided into 2 groups according to administered cells: hematopoietic SCs or cells obtained from a line of rat hepatoma. Cell injection was performed during a planar dynamic acquisition. Regions of interest were positioned to plot time activity curves on heart, lungs, liver and spleen. Blood cell clearance was evaluated according to common stochastic analysis approach. Either fraction of dose in each organ at the end of the experiment or computing the slope of regression line provided by Patlak or Logan graphical approach estimated cell recruitment. At the end of the study, animals were sacrificed and the number of cells retained in the same organs was estimated by in vitro counting. Results: Cell number, documented by the dose fraction retained in each organ at imaging was consistently higher with respect to the "gold standard" in vitro counting in all experiments. An inverse correlation was observed between degree of overestimation and blood clearance of labeled cells (r=-0.56, P

A real-time velocity (RTV) diagnostic based on active charge-exchange recombination spectroscopy is now operational on the National Spherical Torus Experiment-Upgrade (NSTX-U) spherical torus (Menard et al 2012 Nucl. Fusion 52 083015). The system has been designed to supply plasma velocity data in real time to the NSTX-U plasma control system, as required for the implementation of toroidal rotation control. Measurements are available from four radii at a maximum sampling frequency of 5 kHz. Post-discharge analysis of RTV data provides additional information on ion temperature, toroidal velocity and density of carbon impurities. Examples of physics studies enabled by RTV measurements from initial operations of NSTX-U are discussed.

Combined neutral beam injection and fast wave heating at cyclotron harmonics accelerate deuterium fast ions in the National Spherical Torus Experiment (NSTX) and in the DIII‐D tokamak. Acceleration above the injected energy is evident in fast‐ion D‐alpha (FIDA) and volume‐average neutron data. The FIDA diagnostic measures spatial profiles of the accelerated fast ions. In DIII‐D, the acceleration is at a 4th or 5th cyclotron harmonic; the maximum enhancement in the high‐energy FIDA signal is 8–10 cm beyond the resonance layer. In NSTX, acceleration is observed at five harmonics (7–11) simultaneously; overall, the profile of accelerated fast ions is much broader than in DIII‐D. The energy distribution predicted by the CQL3D Fokker‐Planck code agrees fairly well with measurements in DIII‐D. However, the predicted profiles differ from experiment, presumably because the current version of CQL3D uses a zero‐banana‐width model.

The aim of this report is to describe a case of uterine arteriovenous malformation that occurred in a 54-year-old postmenopausal woman referring recurrent postmenopausal bleeding, after two years of tamoxifen therapy.Medical therapy with GnRh agonists was unsuccessful. Ultrasound and Doppler flow ultrasound scanning were normal and the following hysteroscopy was normal as well.Hysterosonography performed on the patient made us suspect the presence of an intracavitary vascular lesion which was confirmed histologically after hysterectomy.In our case hysterosonography allowed us--by creating optimal contrast between the uterine wall and the uterine cavity--to suspect and identify the lesion and to recognize the typical ultrasound findings of this pathology not visualized with standard transvaginal ultrasound.

Pseudoxanthoma elasticum (PXE) is a rare hereditary disease characterised by systemic degeneration of elastic tissue. Calcification of elastic fibres seen histologically is pathognomonic for the disorder. Most pseudoxanthoma elasticum patients show no serious complications during pregnancy.We report a case of a 29-year-old white woman with pseudoxanthoma elasticum, who delivered a healthy infant at the 35th week by cesarean section after an uneventful pregnancy. Sonographic and histological placental findings are described.Pregnancy in a patient with pseudoxanthoma elasticum presents some problems such as the evolution of the disease in the soon to be mother and the influence of the disease on the pregnancy. In our case there were no fetal-maternal complications related to the disease except skin lesion aggravation.

Cytogenetic abnormalities and paroxysmal nocturnal haemoglobinuria (PNH) phenotype are frequent findings in aplastic anaemia patients treated with immunosuppressive therapy (IST). In this study we investigated whether the appearance of clonal haemopoiesis influences patient outcome and survival. 97 patients entered this study and were followed from the onset of the disease for a median follow-up (FU) of 53 months. 93% are alive, 56% achieved complete remission, 30% partial remission, both transfusion independent, and 14% did not respond. Three groups were identified: (A) patients without evidence of emerging clones (71/97); (B) patients who acquired chromosomal abnormalities (13/97); (C) patients who showed low expression of glycosyl phosphatidylinositol anchored proteins (GPI-AP) (PNH phenotype) at presentation or later (16/97). Three patients showed both PIG-AP deficiency and chromosomal abnormalities. The actuarial survival of patients without clonal haemopoiesis (n = 71) at 6 years was 95%, for patients with chromosomal abnormalities (n = 13), 88%, and for patients with PIG-AP deficiency (n = 16), 89%. There was no difference in the probability of becoming transfusion independent in the three groups (93%, 92% and 88% respectively). This study confirmed that a proportion of severe aplastic anaemia (SAA) patients exhibit clonal markers during the time after IST, often coexisting with cytogenetically or phenotypically normal haemopoiesis. There was no significant clinical impact of these abnormalities on transfusion independence and survival at the median follow-up of 4 years.

We carried out studies to quantify Ph-negative progenitors both in steady state and during regeneration after chemotherapy and G-CSF in 23 newly diagnosed chronic myeloid leukaemia (CML) patients (group A) and in 14 individuals more than a year from diagnosis (nine in chronic and five in accelerated phase, group B). In steady-state bone marrow, Ph-negative long-term culture initiating cells (LTC-IC) and Ph-negative colony-forming-cells (CFC) were detected in 18/23 and 14/23 patients of group A versus 3/14 and 3/14 patients of group B (P0.001 and P0.02, respectively). The absolute number of mobilized Ph-negative progenitors was markedly higher in group A versus group B (P0.02 for LTC-IC, P0.003 for CFC). 12/16 newly diagnosed patients mobilized Ph-negative LTC-IC only and the yield was in the range of normal allogeneic donors. Overall the frequency of Ph-negative LTC-IC in the bone marrow predicted the yield of Ph-negative LTC-IC mobilized into peripheral blood (P0.001). The bone marrow frequency of Ph-positive LTC-IC was considerably lower than the normal counterpart. Taken together, these findings suggest that normal progenitors are relatively well preserved in newly diagnosed CML patients, but tend to rapidly decline with time. This observation helps in the understanding of the pathogenesis of CML and has potential implications for autografting. The optimal time for a successful collection of Ph-negative circulating progenitors would appear to be soon after diagnosis.

We previously reported that patients with acquired severe aplastic anemia (SAA) treated with antilymphocyte globulin (ALG), 6-methylprednisolone, cyclosporin A (CyA) and granulocyte colony-stimulating factor (G-CSF) can mobilize peripheral blood hemopoietic progenitors (PBHP). The aim of the present study was to assess phenotypic and functional properties of these PBHP.We studied seven patients who underwent 43 leukophereses (median 5) between day +30 and +80 following ALG, while in treatment with CyA and G-CSF. Mobilized peripheral blood hemopoietic progenitors were analyzed using surface markers, conventional assays for clonogenic cells (CFU-GM, BFU-E, CFU-GEMM) as well as the recently developed assay for long-term culture initiating cells (LTC-ICs).The proportion of CD34+ cells ranged between 0% and 5.4% (median 0.3%), CD34+DR between 0% and 3.5% (median 0.1%) and CD8+ cells between 3.3% and 56% (median 31%). When light density mononuclear cells (MNC) were plated in vitro, we could grow colony-forming units-granulo-macrophage (CFU-GM) (range 0-45/10(5) MNC; normal controls 21-200/10(5) MNC), burst-forming units-erythroid (BFU-E) (range 0-5/10(5) MNC; normal controls 0-6/10(5) MNC), multipotent colonies (CFU-GEMM) (range 0-3/10(5) MNC; normal controls 0-6/10(5) MNC) and high proliferative potential colony-forming cells (HPP-CFC) (range 0-3.4/10(5) MNC). We studied long-term culture-initiating cells (LTC-ICs) in 18 leukophereses from 4 patients; in 7/18 samples LTC-ICs were grown at low frequency (range 0.4-2/10(6) MNC) (normal controls 5-130/10(6) MNC), and in one patient in the absence of CFU-GM growth. The total yield of LTC-ICs in two patients was 7.64 and 10.5 x 10(2)/kg of body weight.This study suggests that cells with the phenotype and in vitro function of early hemopoietic progenitors are found, though in small numbers, in the peripheral blood of patients with SAA after treatment with immunosuppressants and prolonged G-CSF administration. Whether G-CSF-mobilized progenitors contribute to hemopoietic recovery in these patients remains to be determined.

We have previously reported that mobilization of Philadelphia (Ph) chromosome-negative progenitors is possible in a significant number of Ph1-positive acute lymphoblastic leukaemia (ALL) and chronic myelogenous leukaemia (CML) patients. In this pilot study we employed the same approach for patients with RAEB-t, secondary AML (sAML) and therapy-related AML (t-AML). All patients except one had double or complex cytogenetic abnormalities in marrow cells before mobilization therapy. All patients received an idarubicin-containing regimen (mini-ICE protocol) followed by rh-G-CSF and the first leukapheresis was performed as they were recovering from aplasia. In six out of nine patients the leukapheresis product was entirely karyotypically normal, combined with a significant number of CFU-GM. CD34+ cells and LTC-IC. Recovery time from mobilization therapy was short and no patient died as a result of the procedure. To date, three patients have undergone autografting using their karyotypically normal collections, of which two (sAML) are alive with karyotypically normal marrow a few months after autografting.

The study was devised to evaluate whether it was possible to collect Philadelphia-negative precursor cells in patients with chronic myeloid leukaemia. The approach was based on previous experience showing that complete remission (Ph-negative bone marrow cells) is rarely achieved after chemotherapy and is very short-lasting. We decided to explore whether it was possible to collect Ph-negative precursor cells in peripheral blood during the early phase of haemopoietic recovery. These data show that: the collection of Ph-negative precursor cells occurred in 12/16 (75%) patients mobilized within one year of diagnosis (group A) versus 12/33 (36%) in patients with a history of more than one year of disease (group B). Furthermore the numbers of Ph-negative precursor cells were significantly much higher at diagnosis. Ten patients mobilized at diagnosis were subsequently autografted with such Ph-negative precursor cells. Five of them remain Ph-negative from 4 to 12 months while the other five have percentages of Ph-positive cells in their marrow ranging from 20% to 70%. In this stage of the disease the procedure is safe and associated with a very good compliance. Occasional restoration of Ph-negative haemopoiesis could be observed up to 40 months after autograft, in patients of group B, but most of patients revert to Ph-positive haemopoiesis. in conclusion these data suggest that it is possible to restore Ph-negative haemopoiesis in 70% of patients mobilized at diagnosis. This percentage represent the highest one can obtain without allogeneic BMT, and this includes patients who never would have been cytogenetic responders to IFN-alpha. Whether and how long for Ph-negative status can be maintained is a matter for future observation and study.

Twenty-three patients with chronic myelogenous leukemia in early chronic phase (ECP) and not previously treated with alpha-interferon (IFN-alpha) (10 patients), in ECP but pretreated with IFN-alpha (12 months) (seven patients) and in late chronic phase (LCP) pretreated with IFN-alpha (12 months) (six patients) underwent autografting with Philadelphia (Ph) chromosome-negative blood progenitor cells (BPCs) (20 patients), or partially/totally Ph-positive BPCs (three patients), previously mobilized during the early phase of recovery after aplasia induced by intensive chemotherapy. The conditioning regimen consisted of high-dose chemotherapy alone or followed by total body irradiation (TBI). Recombinant G-CSF was given after BPCs infusion on day +8. All patients in ECP not pretreated with IFN-alpha are alive and five of them are Ph-negative in the marrow after autografting. Six of seven patients autografted with Ph-negative BPCs in the group of ECP pretreated with IFN-alpha (12 months) are alive and two of them are still Ph-negative in the marrow. In the same group, the only patient transplanted with partially Ph-positive BPCs, died of blastic transformation 2 months after reinfusion. Three patients (two patients autografted with Ph-negative BPCs and one patient with Ph-positive BPC) in the group of LCP pretreated with IFN-alpha12 months are alive but Ph-positive after autografting. The other three patients of the same group died of procedure-related toxicity (two patients) and blastic transformation (one patient). Seventeen patients (10/10 ECP not pretreated with IFN-alpha; 5/7 ECP pretreated with IFN-alpha and 2/6 LCP pretreated with IFN-alpha) of 23 autografted patients were treated with IFN-alpha +/- IL-2. Toxicities after autografting were mostly related to myelosuppression, particularly thrombocytopenia. All patients of the two groups pretreated with IFN-alpha developed febrile episodes during the aplastic phase following BPCs reinfusion. No patient autografted in ECP and those not pretreated with IFN-alpha developed febrile episodes. This is also probably due to the use of i.v. antibiotic and antimicotic prophylaxis when neutrophils wereor = 1 x 10(9)/l after autografting. Greater toxicity was observed in patients pretreated with IFN-alpha, being lethal in two cases in LCF. In conclusion, the "in vivo' manipulation approach employed in our institution is a safe procedure and it results in a high collection of Ph-negative cells in the blood if the cells are harvested: (1) in early chronic phase; (2) in early phase of recovery after chemotherapy-inducing aplasia; (3) in patients not extensively pretreated with IFN-alpha. The data presented here have shown encouraging trends in chronic phase of CML and offer new perspective for patients without an HLA-identical donor or for patients who do not respond to IFN-alpha.

We have previously demonstrated that Philadelphia negative (Ph-ve) hemopoietic cells can be collected by leukaphereses after an acute leukemia-like chemotherapy during the early hemopoietic recovery in patients with chronic myeloid leukemia (CML). In this study we have evaluated whether these collections contain very primitive hemopoietic cells defined as 'long-term culture initiating cells' (LTC-IC) and whether these cells belong to the Ph-positive or Ph-negative population. Twenty-eight out of 76 cytaphereses collected in 15 patients with CML proved to contain Ph-ve cells only (six patients), 21 showed only Ph+ve cells (five patients), and 27 a mixture of Ph+ve and Ph-ve cells (four patients). In cytaphereses containing Ph-ve cells only, we found variable numbers of LTC-ICs, more consistently when we mobilized patients in the first 3 months from diagnosis. In three cases cytogenetic analysis on LTC-ICs and CFU-GM confirmed results obtained on fresh samples. Ph-positive collections were devoid of LTC-ICs except for 2/21 samples. However, their cytogenetic analysis revealed a small number of Ph-negative progenitors. LTC-ICs were randomly detected in mixed (Ph+ve and Ph-ve) collections. In conclusion these data indicate that, in a consistent proportion of chronic myeloid leukemia patients, intensive chemotherapy is able to recruit Ph-ve LTC-ICs in to the peripheral blood. Moreover these data provide the biological basis for developing autografting programs with Ph-negative cells.

The polymerase chain reaction (PCR) was used to amplify the bcr/abl transcript as a marker of minimal residual disease (MRD) in 76 patients with chronic myeloid leukemia (CML) subjected to allogeneic BMT and in complete hematological remission. We examined 56 patients transplanted in chronic phase (CP) and 20 in advanced phase (AD), including 16 in accelerated phase and four in blastic transformation. A total of 135 samples collected between 4 and 105 months from BMT were analyzed and the PCR analysis was positive in 33 (24%) samples from 20 patients. The bcr/abl chimeric transcript was detected in 7/13 (54%) patients analyzed within 1 year and in 21/88 (23%) beyond 1 year from BMT. Fluctuation of the residual disease at the molecular level in individual patients was recorded. The results have been correlated with a number of clinical parameters obtained before and after BMT; among the tested variables only the phase of the disease at BMT was associated with higher frequency of PCR positivity after BMT. The probability of finding persisting disease 1 year beyond BMT was significantly higher (P = 0.00005) in patients allografted in AD (14/26, 54%) as compared to patients grafted in CP (7/62, 11%). At any interval from BMT the difference between the two groups remained statistically significant: the bcr/abl transcript was present in 5/31 patients transplanted in CP compared to 9/15 patients transplanted in AD (P = 0.003) between 12 and 36 months from BMT, and in 2/31 CP vs 5/11 AD patients (P = 0.008) beyond 36 months from BMT.(ABSTRACT TRUNCATED AT 250 WORDS)

Neuroleptic malignant syndrome (NMS) is a life-threatening reaction often related to neuroleptic drugs, characterized by rigidity, hyperthermia, altered consciousness, and fluctuating blood pressure. We present a case of NMS that followed a doubled oral dose of a drug compound: tranylcypromine sulfate, a monoamine oxidase inhibitor, and trifluoperazine (neuroleptic). The case was complicated by rhabdomyolisis and disseminated intravascular coagulation. It was treated successfully with dantrolene sodium and generous fluid therapy without using neuromuscular blocking agents or dopamine agonists.