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Biomedical subjects

L Noens

Publications and source records attributed to L Noens.

At least 19 recordsLinked to original sources
PubMed2006

Long-term survival data from a phase 3 study of Filgrastim as an adjunct to chemotherapy in adults with de novo acute myeloid leukemia.

We previously reported the results of a double-blind, placebo-controlled study of Filgrastim in patients with de novo AML undergoing induction and consolidation chemotherapy. The study demonstrated that Filgrastim was effective and well tolerated and had no impact on complete remission or survival. We now report follow-up data on these patients, assessing long-term effects with emphasis on prognostic indicators. After a median follow-up of 7 years, 434 (83%) patients were dead, 73 (14%) were alive, and 14 (3%) were lost to follow-up. The proportions of deaths were similar in the Filgrastim (83%) and placebo (84%) groups. No differences in median time to death (1.04 years Filgrastim, 1.13 years placebo; P = 0.97) or median disease-free survival (0.86 years Filgrastim, 0.79 years placebo; P = 0.52) were evident. Proportional hazard modeling identified age, performance status, and French-American-British subtype as independent predictors for survival (P < 0.001, P = 0.005, and P = 0.036, respectively), whereas cytogenetic status was not (P = 0.118). Filgrastim had no effect on overall survival in any of these subgroup analyses as none of the treatment comparisons were statistically significant. These findings indicate that Filgrastim can be effectively used to support patients with AML undergoing induction and consolidation chemotherapy without worsening long-term disease outcome.

Acute Disease↗
PubMed2004

Risk-adapted induction and consolidation therapy in adults with de novo AML aged </= 60 years: results of a prospective multicenter trial.

We treated 305 de novo acute myeloid leukemia (AML) patients aged </=60 years with risk-adapted therapy. Patients with CBF leukemias or normal karyotype and good response to induction I [</=5% bone marrow (BM) blasts on day 15] were considered standard risk (SR), all others as high risk (HR). Patients with t(15;17) were excluded. Chemotherapy comprised double induction followed by early consolidation. As late consolidation, SR patients received high-dose cytarabine/daunorubicin (AraC/DNR). SR patients with normal karyotype were allotransplanted from HLA-matched siblings. HR patients were allotransplanted or if no sibling donor was available autotransplanted with peripheral blood progenitor cells (PBSC) harvested after early consolidation. 89% of the SR and 60% of the HR patients achieved CR. The continuous complete remission (CCR) rate at 80 months (median follow-up: 48 months) was 48% for SR and 32% for HR. The CCR rate was 54% for t(8;21), 47% for normal karyotype, and 33% for inv(16) patients. In the HR group, the CCR rate did not differ significantly for patients with bad response to IVA-I, unfavorable karyotype, or both. Forty-five HR patients were autotransplanted (n=20) or allotransplanted (n=25). The probability of CCR was 44% for autotransplantation vs 33% for allotransplantation. In conclusion, our risk-adapted strategy produced encouraging results in SR patients. Early response to therapy is a strong prognostic factor that predicts the probability of CR and long-term outcome.

Adolescent↗
PubMed2002

Molecular cytogenetic analysis of 10;11 rearrangements in acute myeloid leukemia.

MLLT10 (previously called AF10) is a moderately common MLL fusion partner predominantly occurring in acute monoblastic leukemia (AML-M5). 10;11 rearrangements require at least three breaks in order to generate an in-frame MLL-MLLT10 fusion as a result of the opposite orientations of both genes on the respective chromosome arms. In this study, we describe a detailed molecular cytogenetic analysis of MLL-MLLT10 positive 10;11 rearrangements in two patients. We observed an as yet unreported chromosomal mechanism with at least four breakpoints, leading to MLL-MLLT10 gene fusion in a 24-year-old male. An inversion of 11q13-q23 with a breakpoint in the MLL gene was followed by an additional break 3' of MLL prior to insertion of the 11q segment into MLLT10. In a second patient, a 37-year-old male with AML-M5b, molecular cytogenetic analysis of an apparent 10;11 reciprocal translocation showed an intrachromosomal inversion of 3'MLLT10followed by a reciprocal translocation between 10p12 and 11q23. Review of the literature showed that all cases were the result of an inversion of either 10p or 11q followed by translocation 10p;11q or insertion of the inverted segment into MLLT10 or MLL.

Acute Disease↗
PubMed2002

18FDG PET versus high-dose 67Ga scintigraphy for restaging and treatment follow-up of lymphoma patients.

To date, only one published study has directly compared 67Ga scintigraphy (low dose, planar) with planar dual-head gamma camera 18F-fluorodeoxyglucose (18FDG) imaging for the purpose of treatment follow-up monitoring in lymphoma patients, and no data on restaging are available. The present study reports the direct comparison of high-dose (297-370 MBq) 67Ga planar and single photon emission computed tomography (SPECT) imaging and conventional 18FDG positron emission tomography (PET) for restaging and treatment follow-up of lymphoma patients versus a gold standard consisting of morphological imaging, including plain radiography and computed tomography (CT) scanning, bone marrow examination and long-term follow-up (<12 months). Sixteen patients, 10 with non-Hodgkin's lymphoma and six with Hodgkin's disease, were included (10 men, six women; median age, 43 years; range, 16-64 years). The median follow-up time was 27 months (range, 12-34 months). In two patients, 67Ga and 18FDG PET (370 MBq) were performed twice, resulting in 18 cross-sectional episodes. In 11 episodes, the results obtained by both imaging modalities were in agreement with regard to the presence or absence of disease when compared with the gold standard. However, the abnormalities found on 18FDG PET were always more extensive. In two episodes, 67Ga imaging normalized after treatment, whereas PET showed significant regression followed by subsequent normalization. In four additional episodes, 67Ga images were negative, whereas 18FDG PET visualized non-tumour-related pathology, such as lung infection, rib fracture or dense thymic tissue. In one gold standard-negative patient, the underlying cause of sternal FDG uptake remained undetermined. The data presented, although limited in number, suggest that 18FDG PET performs better than Ga imaging in monitoring lymphoma disease status. However, a correlation with clinical history and a knowledge of the characteristics of benign lesions are mandatory. Further studies are recommended.

Adolescent↗
PubMed2000

Pyoderma gangrenosum as an early revelator of acute leukemia.

Bullous pyoderma gangrenosum is an atypical, more superficial variety of the classical pyoderma and is often associated with myeloproliferative disorders. We present the case of a patient who presented initially with subcutaneous nodules and who developed bullous lesions afterwards. Histological evaluation showed the presence of neutrophilic infiltrates in both lesions. A few months after the diagnosis of bullous pyoderma gangrenosum, an underlying leukemia was revealed. Our case illustrates the importance of regular blood and bone marrow examinations in patients with atypical bullous pyoderma gangrenosum, resulting in a rapid diagnosis of the underlying disease.

Female↗
PubMed1999

Membrane filtration test for rapid presumptive differentiation of four Candida species.

A rapid enzymatic two-step test for the presumptive differentiation of four Candida species commonly occurring in various clinical samples is described. The technique involves membrane filtration of a liquid sample, followed by preincubation of the membrane filter on Sabouraud glucose agar supplemented with ticarcillin-clavulanic acid to yield microcolonies. In a separate assay step, parts of the filter are placed on absorbent pads impregnated with fluorogenic 4-methylumbelliferyl (4-MU) enzyme substrates (4-MU-N-acetyl-beta-D-galactosaminide, 4-MU-phosphate, 4-MU-pyrophosphate, and 4-MU-beta-D-galactoside) in combination with 0.1% digitonin acting as a membrane permeabilizer. The membrane filter in contact with the assay medium is incubated to allow cleavage of the enzyme substrate, resulting in fluorescent microcolonies under long-wavelength UV light. This approach, tested on 301 clinical samples, is able to presumptively differentiate C. albicans, C. glabrata, C. krusei, and C. tropicalis and to distinguish them from other Candida spp. in about 9 to 11 h. Overall agreement with the conventional methods of 94.4% (one Candida species present in the sample) to 83.8% (multiple Candida spp. present) was obtained. The false-negative rates with reference to identification by traditional methods were 1.3% (single species) and 3.8% (multiple species).

Candida↗
PubMed1999

The belgian experience in unrelated donor bone marrow transplantation: identification of center experience as an important prognostic factor.

BACKGROUND AND OBJECTIVE: We reviewed all unrelated donor bone marrow transplants (UDBMT) performed in Belgium up to December 1995 to identify prognostic factors for relapse, transplant-related mortality and survival. DESIGN AND METHODS: A total of 163 UDBMT were performed in 92 males and 71 females aged 1-55 (median 26) years. Patients were transplanted for ALL (n=35), AML (n=34), CML (n=51), other myeloid malignancies (n=14), SAA (n=21) or miscellaneous other diseases (n=8). Most patients had advanced disease; a few patients were in CR1 (n=10) or early chronic phase (CP) of CML (n=5). RESULTS: Overall survival at 5 yrs was 17% (95% confidence interval: 8-32%), but survival was significantly better for patients with non-malignant disorders (55% at 4 yrs). The relapse rate +/-SE was projected to be 40 (28-54)% at 5 yrs, 36 (20-56)% for standard-risk and 68 (43-85)% for high-risk malignancies (p=0.0029). There was no relapse in CML patients transplanted in 1st CP compared to 68% at 4 yrs with more advanced CML (p=0.0033). Grade II-IV acute graft-versus-host disease (aGVHD) occurred in 55% by day 100 and was strongly modulated by age, ranging from 41% in <20-yr-old to 80% in >40-yr-old patients (p=0. 0021). Transplant-related mortality (TRM) was projected to be 72 (52-87)% at 5 yrs including 2 very late deaths from lung fibrosis and secondary cancer. Main causes of death were original disease in 27, secondary malignancy in 2, GVHD in 28, interstitial pneumonia in 21, other infections in 19, and miscellaneous toxic causes in 21 patients. In multivariate analysis, the relapse rate was strongly dependent on the disease status (p=0.0029), TRM being significantly worse with older age (p=0.0049), and overall survival being significantly worse in more advanced disease (p=0.0006), after a second transplant (p=0.0166), in centers of smaller size (p=0.0316) and in older patients (NS). INTERPRETATION AND CONCLUSIONS: Although results have improved somewhat in recent years, UDBMT remains a procedure with a high TRM. UDBMT should be performed in patients with less advanced diseases and in centers with more experience, particularly in the treatment of adult patients.

Adolescent↗
PubMed1997

A randomized, double-blind, placebo-controlled, phase III study of filgrastim in remission induction and consolidation therapy for adults with de novo acute myeloid leukemia. The International Acute Myeloid Leukemia Study Group.

The safety and efficacy of filgrastim as an adjunct to acute myeloid leukemia (AML) induction and consolidation therapy was assessed in this prospective double-blind, randomized, placebo-controlled, multicenter trial. A total of 521 consecutive de novo AML patients aged 16 or more years were randomized to receive filgrastim (5 microg/kg/d subcutaneously) or placebo after standard induction as well as consolidation chemotherapy. Blinded study drug was given from 24 hours after chemotherapy until the absolute neutrophil count was >/=1.0 x 10(9)/L for 3 consecutive days. The overall complete remission rate was 68%. After a median follow-up of 24 months (range 5 to 40) the median disease-free survival was 10 months (95% confidence interval [CI], 8.7 to 10.8) and the median overall survival was 13 months (95%CI, 12.2 to 14.6). These did not differ between treatment groups. Patients receiving filgrastim experienced neutrophil recovery 5 days earlier after induction 1 than those receiving placebo (P < .0001). This was accompanied by reductions in the duration of fever (7 v 8.5 days; P = .009), parenteral antibiotic use (15 v 18.5 days; P = .0001), and hospitalization (20 v 25 days; P = .0001). Similar reductions were seen after induction 2 and the consolidation courses. There was a significant reduction in the number of patients requiring systemic antifungal therapy in the filgrastim group during induction treatment (34% v 43%; P = .04). In conclusion, filgrastim is safe in that it had no negative impact on the prognosis of the AML patients. In addition, it effectively reduced the duration of neutropenia, leading to significant clinical benefits by reducing the duration of fever; requirement for parenteral anti-infectives, specifically amphotericin B; and the duration of hospitalization.

Adolescent↗
PubMed1997

Aseptic necrosis. A scintigraphic imitator of osseous involvement in Ga-67 avid lymphoma.

Based on the data by Armas et al, avascular necrosis, a not uncommon treatment-associated complication in patients with lymphoma, it should be easily distinguishable from osseous lymphomatous involvement in patients with Ga-67 avid lymphoma. In avascular necrosis, Ga-67 uptake will be either absent, decreased, or normal, whereas in lymphoma Ga-67 uptake will be increased. The authors present a patient with Hodgkin's disease who had new foci of simultaneously increased Ga-67 and Tc-99m MDP uptake because of avascular necrosis as proven by biopsy and long-term follow-up. The authors hypothesize that a possible-explanation for the discrepancy between this patient report and the series by Armas et al may be that increased Ga-67 is a delayed phenomenon related to healing.

Adult↗
PubMed1996

Erythromelalgia: a clue to the diagnosis of polycythemia vera.

We report the case of a 74-year-old woman with recurrent episodes of symmetrical congestion and erythema in the distal lower legs causing a burning distress. Laboratory and clinical investigations revealed an underlying myeloproliferative disorder. The cutaneous symptoms were atypical of erythromelalgia. Salicylates and treatment of the underlying polycythemia were able to eliminate the skin lesions but not entirely suppress the subjective discomfort.

Aged↗
PubMed1992

Acquired hypolipoproteinemia.

We present a six-year follow-up of a boy with a novel type of hypolipoproteinemia, with clinical and biochemical features distinct from classical hypoalphalipoproteinemias. There were abnormally low concentrations of total and high-density lipoprotein (HDL) cholesterol, apolipoprotein (apo) B, apo A-I, and apo A-II, and the phospholipids were decreased. The most striking abnormality was an extra fraction containing mainly phospholipids and apo A-I in the HDL3 subfraction. This fraction is reminiscent of concentric 20- to 50-nm-diameter lamellar phospholipid liposomes. Plasma lecithin:cholesterol acyltransferase activity was strongly decreased. We noted a persisting polyclonal hypergammaglobulinemia, hematological abnormalities (hemolytic anemia and thrombocytopenia), and a progressive splenomegaly. After the five-year follow-up, the patient had recurrent severe infections; moderate hematuria and proteinuria developed gradually. Treatment with corticosteroids and immunoglobulins improved thrombocytopenia and hypolipoproteinemia. These clinical and biochemical findings differ from those in the known primary and secondary hypo-alpha-lipoproteinemia syndromes. Although investigation of the relatives suggests a familial predisposition for hypo-alpha-lipoproteinemia, the subject's condition can be regarded as acquired.

Adolescent↗
PubMed1991

Immunosuppressive treatment of venous allografts.

In order to evaluate whether temporary immunosuppressive therapy is able to improve the results obtained with viable venous allografts and achieve better results than with synthetic grafts, 142 arterial reconstructions were performed in mongrel dogs bypassing their ligated femoral arteries. Histological as well as immunological studies were performed and patency determined by weekly palpation and regular angiography. The 6-month cumulative patency rates were: Group I: synthetic grafts (a) Dacron: 48%, (b) plasma-TFE: 53%. Group II: fresh grafts (a) autografts: 100%, (b) allografts: 37%, (c) allografts treated with cyclosporin 4 mg kg-1 daily for 1 month: 74% (100% after 1 month). Group III: grafts preserved in Hanks' solution with 15% DMSO at -160 degrees C for 1 month (a) autografts: 77%, (b) allografts: 35%, (c) allografts treated with methylprednisolone 1 mg kg-1 daily: 38%, (e) allografts treated with cyclosporin and methylprednisolone: 83%. Group IV: human saphenous veins implanted as xenografts and treated with cyclosporin and methylprednisolone: 18%. Immunosuppressive therapy with cyclosporin seems to be able to prevent early thromboses due to rejection seen after implantation of viable fresh or cryopreserved venous allografts, and the results are significantly better than those obtained with synthetic grafts. Tissue matching might further improve these results. This study suggests that cryopreserved venous allografts could be used for the creation of a vein-bank and their use, in combination with tissue typing and temporary immunosuppressive therapy may be warranted for arterial reconstructions when autologous saphenous vein is not available.

Animals↗