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S Tauro

Publications and source records attributed to S Tauro.

12 recordsLinked to original sources
PubMed2005

Theoretical optimization by genetic algorithm of delayed extraction parameters for a matrix-assisted laser desorption/ionization time-of-flight mass spectrometer.

This paper presents the application of a genetic algorithm (GA) to optimize the operating parameters, namely pulse voltage and extraction delay time, when using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOFMS). Simulations predict the presence of several combinations of these parameters that give a local maximum. The aim is to locate the optimal combination (a global maximum) of pulse voltage and extraction time delay in order to focus the ions of a particular m/z value to achieve the best resolution in a given instrumental geometry. The GA locates the global maximum quickly. The results indicate that it may be possible to achieve very high resolving power by using delayed extraction (DE)-MALDI-TOFMS with parameters obtained from the GA.

Algorithms↗
PubMed2005

Rituximab is effective in the management of refractory autoimmune cytopenias occurring after allogeneic stem cell transplantation.

Autoimmune haemolytic anaemia (AIHA), immune thrombocytopenia (ITP) and autoimmune neutropenia (AIN) are well-recognised complications of allogeneic stem cell transplantation (SCT), but have previously only been reported in the context of myeloablative conditioning regimens. Management of AIHA, ITP or AIN occurring after allogeneic SCT is unsatisfactory since they frequently prove refractory to conventional therapies including splenectomy. As a consequence, autoimmune cytopenias occurring after allogeneic SCT are associated with substantial morbidity and mortality. We report four patients who developed AIHA or ITP after allogeneic transplantation -- three of which occurred after a reduced-intensity conditioning (RIC) regimen. All patients demonstrated a complete response to Rituximab, having failed to respond to conventional treatment including high-dose prednisolone and intravenous immunoglobulin (IVIg). We conclude that Rituximab can be a valuable agent in the management of autoimmune cytopenias occurring after allogeneic SCT and that autoimmune cytopenias may be a hitherto unrecognised complication of RIC regimens.

Adult↗
PubMed2003

High-hyperdiploidy in Philadelphia positive adult acute lymphoblastic leukaemia: case-series and review of literature.

Patients with Philadelphia positive (Ph(+)) adult acute lymphoblastic leukaemia (ALL) have a poor prognosis. Stem cell transplantation (SCT) is increasingly being recognised as the treatment of choice in eligible patients with Ph(+)ALL, but disease-relapse remains a problem in a proportion of patients prior to and after SCT. Genetic abnormalities in addition to the Ph chromosome may influence the biology and clinical course of ALL, but there are not many studies on the potential genetic heterogeneity of adult Ph(+)ALL and clinical outcomes. Here, we report on five patients with ALL who were double Ph(+) and also had a high-hyperdiploid karyotype (Ph(+)/hyperdiploid) at diagnosis. In contrast to the presence of the Ph(+) chromosome, high-hyperdiploidy (>50 chromosomes) as the sole karyotypic abnormality in ALL is associated with a favourable clinical outcome. In our series, four patients with a Ph(+)/hyperdiploid karyotype achieved a cytogenetic remission after induction chemotherapy and proceeded to stem cell transplantation (SCT). The fifth had five subclones including Ph(+)/hyperdiploid, as well as those that were only Ph(+); the latter emerged as the dominant clone after induction therapy and the patient died of disease-relapse. Of the patients who underwent SCT, only one relapsed, but achieved a durable remission with donor lymphocyte infusions. Thus, it is conceivable that the presence of high-hyperdiploidy as an additional karyotypic abnormality may confer a better prognosis to Ph(+)ALL, presumably by altering the kinetics of Ph(+) neoplastic cells. We have discussed these results in the context of recent studies on the significance of high-hyperdiploidy in Ph(+) adult ALL.

Adult↗
PubMed2003

Stem cell transplantation after salvage therapy with high-dose cytarabine and amsacrine in adults with high-risk leukaemia.

Stem cell transplantation (SCT) may be the only curative option for patients with relapsed or refractory leukaemia, that is, high-risk (HR) leukaemia. Several salvage regimens have been used to cytoreduce disease before SCT, but disease progression or treatment toxicity limits numbers of patients receiving SCT. Here, we report our experience with high-dose cytarabine and amsacrine (Ara-amsa) to salvage patients with HR-leukaemia in the context of SCT. A total of 34 patients with HR-leukaemia (20 AML, 12 ALL, two advanced CML) received 3 g/m(2)/day cytarabine for 5 days and amsacrine 200 mg/m(2)/day for 3 days. Disease response was observed in 62% of patients. Toxicity was limited to neutropenic fever, one patient developed cerebellar toxicity and there was one treatment-related death. A total of 17 patients proceeded to SCT (12 allografts and five autografts). Median survival (OS) of all patients was 10.8 months (95% CI 7.8-21). Patients who were consolidated with SCT after salvage therapy had a superior median OS of 29.4 months (95% CI 12.5-upper limit not reached, n=17) than those who did not receive SCT (6.7 months, CI 1.5-8.6, P<0.0001). Median disease-free survival with SCT (23 months) was higher than after treatment with salvage chemotherapy alone (6.7 months, P=0.0002). Thus Ara-amsa can be used effectively to salvage HR-leukaemia, enabling further consolidation with SCT.

Adolescent↗
PubMed2002

Recovery of renal function after autologous stem cell transplantation in myeloma patients with end-stage renal failure.

The disease-free survival of patients with myeloma and severe renal failure after high-dose melphalan and autologous stem cell rescue is similar to those with normal renal function at the time of the autograft. However, recovery of renal function after intensive treatment is uncommon and patients with end-stage renal failure continue to be dialysis-dependent. We report two patients with myeloma who required regular haemodialysis from diagnosis, but became dialysis-independent after a high-dose melphalan autograft. Thus, in some patients, renal function may be partially salvageable despite the requirement for dialysis at the time of autografting.

Disease-Free Survival↗
PubMed2002

Functional disturbance of marrow stromal microenvironment in the myelodysplastic syndromes.

The potential contribution of abnormal marrow stromal function to ineffective haemopoiesis in the myelodysplastic syndromes is unclear. We have compared the ability of stromal layers from normal (n = 7) and myelodysplastic (n = 9) marrow to alter proliferation and survival of the granulocyte-macrophage colony-stimulating factor/interleukin-3-dependent cell line F-36P. Co-cultures for 72 h in the absence of exogenous cytokines were either in direct contact with stroma or separated by transwell inserts. On normal stromal layers, the ratio of adherent F-36P cells relative to stromal cells increased from a mean of 0.2 +/- 0.01 (s.d.) at 4 h of co-culture to 0.34 +/- 0.08 after 72 h (n = 7). Corresponding values on myelodysplastic stroma (0.2 +/- 0.02 at 4 h and 0.35 +/- 0.05 at 72 h; n = 9) indicated that the ability of myelodysplastic stromal layers to regulate short-term proliferation of F-36P cells may be similar to normal. Apoptosis of F-36P cells was quantified after co-culture with normal or myelodysplastic stroma: results from myelodysplastic co-cultures were standardized as a fraction of values from co-cultures with paired normal stroma (apoptotic ratio). Augmented apoptosis of F-36P cells was detected in 8/9 co-cultures with myelodysplastic stroma (mean = 15.7 +/- 9.7%, n = 9), compared with corresponding normal stroma (mean = 12.4 +/- 4.6%, n = 7, P < 0.05) with a mean apoptotic ratio of 1.4 +/- 0.5 (P < 0.05). There was no correlation between stroma-related apoptosis and FAB type, tumour necrosis factor-alpha concentrations in the culture supernatant or numbers of stromal macrophages, and no evidence of involvement of the Fas pathway. Increased apoptosis was detected in cells grown in transwell inserts over stroma (23.8 +/- 3%, n = 5) compared to adherent cells in cultures with normal stromal layers, but this survival difference was not observed in co-cultures with myelodysplastic stroma. These results suggest that abnormal stromal function in patients with myelodysplastic syndromes may contribute to increased apoptosis of haemopoietic cells within the marrow microenvironment. The effect appears to be dependent on close cellular contact, rather than the release of soluble factors, but the exact mechanism remains unclear.

Aged↗
PubMed2001

Resolution of sarcoidosis after allogeneic bone marrow transplantation with donor lymphocyte infusions.

Abnormalities of immune surveillance may contribute to the development of myeloid malignancy as well as immune-mediated diseases. In leukaemia, allogeneic haemopoietic stem cell transplantation (alloHSCT) has been used to induce disease remission, in part by restoring mechanisms of immune regulation. Although, by the same principle, allogeneic stem cell transplantation is an attractive option for the treatment of immunological disorders, it is unclear whether remission after transplantation is due to pre-transplant conditioning, or modulation of auto-reactive lymphocytes by cells in the allograft. We report the case of a patient with chronic myeloid leukaemia (CML) who received an allogeneic bone marrow transplant (alloBMT) from his brother. He subsequently suffered a cytogenetic and molecular relapse of CML. At the same time, sarcoidosis involving the marrow was diagnosed. He was treated with donor lymphocyte infusions (DLI) and attained remission from CML; in addition, no giant cell granulomas were detected in the marrow, indicating resolution of sarcoidosis. This case illustrates the need for further studies on the role of T cell-based therapies in the management of immune-mediated disorders.

Adult↗
PubMed2001

Assessment of stromal function, and its potential contribution to deregulation of hematopoiesis in the myelodysplastic syndromes.

BACKGROUND AND OBJECTIVES: The regulation of hematopoiesis by marrow stroma in vitro, has been shown to be abnormal in some patients with myelodysplastic syndromes (MDS). This study was performed to assess whether a range of mechanisms may be altered within the MDS microenvironment. DESIGN AND METHODS: The effects of diffusible factors produced by normal or MDS stromal layers on hematopoietic cells were studied by comparing the ability of media conditioned (CM) by normal or MDS stroma to regulate migration of target normal marrow CD34+ cells across 5 microm transmembranes. The ability of CM to stimulate hematopoietic cells was also assessed: changes in membrane polarity of KG-1a cells on exposure to stroma CM were compared. Subsequently, contact-mediated interactions between normal marrow CD34+ cells and normal and MDS stroma were studied: survival of allogeneic normal marrow CD34+ cells on live and glutaraldehyde-fixed normal and myelodysplastic stroma after 24h of co-culture was measured using 7-aminoactinomycin D staining. To determine whether hematopoietic cell survival on normal and MDS stroma was related to oxidative stress within the stromal microenvironment, intracellular superoxide levels, both constitutively and induced by tumor necrosis factor-a were measured within live stromal cells by FACScan analysis of ethidium bromide stained cells. RESULTS: The ability of CM from normal and MDS stroma to regulate short-term migration and activation of hematopoietic cells was similar. The mean percentage of apoptotic CD34+ cells (13+/-11%) adherent to glutaraldehyde-fixed myelodysplastic stroma was higher than on paired fixed normal stroma (11+/-10%) (n=6, p=0.056). Constitutive mean levels of superoxide in myelodysplastic cultures (9.5+/-2.1) were greater than in normal stromal cultures (4.9+/-0.6; n=6). However, following treatment with tumor necrosis factor-a, the mean value for superoxide in myelodysplastic stromal cultures was unchanged (fractional change=0.99+/-0.56), compared with an increase in normal stroma (fractional change=1.6+/-0.1, p<0.05). No correlation was observed between superoxide levels, proportion of apoptotic CD34+ cells and percentage of CD14+ stromal cells [mean 8%, range 0-37% (myelodysplastic); mean 1.3%, range 0-5% (normal)]. INTERPRETATION AND CONCLUSIONS: Abnormalities of stromal function in myelodysplastic syndromes are likely to be heterogeneous in origin: altered matrix molecules and changes in superoxide within stromal cells may contribute to abnormal survival and development of hematopoietic cells within the myelodysplastic marrow microenvironment

Aged↗
PubMed2000

Varicella zoster meningoencephalitis following treatment for dermatomal zoster in an alloBMT patient.

Herpes zoster infections are frequently observed after allogeneic bone marrow transplantation (alloBMT). In the majority of cases, the infection is restricted to specific dermatomes and responds to oral acyclovir, without visceral dissemination. We report the case of a 40-year-old male who developed dermatomal herpetic infection 8 months post alloBMT. The herpetic rash responded well to treatment with high-dose oral acyclovir. However, within a week of cessation of therapy, the patient re-presented with dermatomal zoster and meningoencephalitis. Although the cutaneous lesions resolved with intravenous acyclovir, clinical features of meningoencephalitis persisted, along with evidence of varicella zoster virus (VZV) DNA in cerebrospinal fluid (CSF). A satisfactory response to treatment was observed only after the addition of intravenous foscarnet to acyclovir. Based on our experience with this patient, we suggest that in a subset of alloBMT recipients, late dermatomal herpes zoster infections may respond only partially to treatment with standard oral acyclovir. The use of oral acyclovir preparations with higher bioavailability (valacyclovir) or intravenous acyclovir early on may prevent the considerable morbidity associated with disseminated zoster infection. Bone Marrow Transplantation (2000) 26, 795-796.

Acyclovir↗
PubMed2000

Recurrent penicillin-resistant pneumococcal sepsis after matched unrelated donor (MUD) transplantation for refractory T cell lymphoma.

Patients who undergo splenectomy and recipients of allogeneic marrow (alloBMT) or peripheral stem cell transplantation are at increased risk of overwhelming infection from encapsulated organisms such as Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis. As prophylaxis against these pathogens splenectomised patients are immunised and may also receive antibiotics for life. We report relapsing overwhelming sepsis caused by penicillin-resistant pneumococcus in a patient who was immunised and received prophylactic phenoxymethylpenicillin for 8 months following splenectomy and matched unrelated donor (MUD) marrow transplantation for refractory T cell lymphoma. No obvious focus of sepsis was found during any of the three episodes and S. pneumoniae serogroup 6, subtype 6B was isolated from blood cultures on each occasion. He was treated with i.v. cephalosporins, as the organisms were resistant to penicillin with a minimum inhibitory concentration (MIC) of 2.0, and there was complete resolution of symptoms each time. In the light of recurrent sepsis with this penicillin-resistant organism the decision was made to give prophylactic levofloxacin for the next 12 months. This case illustrates that the choice of prophylactic regimen and the treatment of sepsis in immunocompromised patients remain difficult and challenging issues.

Adult↗