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P Zachée

Publications and source records attributed to P Zachée.

At least 19 recordsLinked to original sources
PubMed2006

High-vs low-dose cytarabine combined with interferon alfa in patients with first chronic phase chronic myeloid leukemia. A prospective randomized phase III study.

A prospective randomized phase III study was performed to evaluate whether intensified cytarabine would induce a higher response rate and longer event-free interval as compared to low-dose cytarabine in chronic myeloid leukemia (CML). One hundred and eighteen patients with CML in early chronic phase entered the study. Twenty-eight out of 32 patients assigned to group A received two cycles of a combination of intensified cytarabine and idarubicin followed by interferon alfa (IFN-alpha) maintenance, 28 patients in group B received standard treatment by a combination of low-dose cytarabine and IFN-alpha. Forty-nine patients with a human leukocyte antigen-identical sibling donor proceeded to allogeneic stem cell transplantation (allo-SCT) and nine patients were excluded from the analysis. Hematological response was observed in 97% of the patients in group A vs 86% of the patients in group B during the first year of treatment. In group A, 16 patients (50%) achieved a major cytogenetic response, which compared to seven patients (25%) with a major cytogenetic response in group B. With a median follow-up of 58 months (range 34-76), event-free survival was not significantly different between arms A and B. The estimated 5-year survival rate was 56% in the intensified arm and 77% in the low-dose arm (P = 0.05). Recipients of allo-SCT showed a 5-year estimated survival rate of 55%. Although intensified cytarabine induced a higher initial percentage of major and complete cytogenetic responses, responses were not sustained by IFN-alpha maintenance therapy.

Adolescent↗
PubMed2006

Pseudo-pulmonary embolism as a sign of acute heparin-induced thrombocytopenia in hemodialysis patients: safety of resuming heparin after disappearance of HIT antibodies.

Heparin-induced thrombocytopenia (HIT) is a syndrome caused by platelet-activating antibodies that recognize complexes of platelet factor 4 (PF4) and heparin. Thrombocytopenia is the most common clinical feature of HIT. HIT can be considered as a hypercoagulable state, with a high risk of thrombosis. Another feature of HIT is an acute systemic reaction that characteristically begins 5-30 min after receiving an intravenous bolus of unfractionated heparin, such as is commonly given for hemodialysis (HD). Here we present 4 patients who developed acute HIT at or near the start of their chronic HD. All patients were anticoagulated with the low-molecular-weight heparin, nadroparin, for HD. Three of our patients underwent surgery approximately 1-2 weeks before developing HIT. All patients presented with an acute systemic reaction during HD. All patients were treated and further dialyzed with lepirudin. Under this treatment we observed a quick recovery of the platelet count, and patients remained symptom-free. Antibodies against the PF4-heparin complex were detected with a combination of a 'quick test' and an enzyme-linked immunosorbent assay test. The likelihood of having HIT previous to the detection of antibodies was estimated with the pre-test probability score criteria. The tests for PF4-heparin antibodies remained positive for an average of 165 days. Three patients underwent a rechallenge with nadroparin after disappearance of the HIT antibodies in their serum. All 3 remained symptomless when they were further hemodialyzed on nadroparin. Our observations indicate that nadroparin can be successfully reintroduced for HD anticoagulation once the patient's HIT antibodies have disappeared.

Aged↗
PubMed2004

Clinical and molecular features of FIP1L1-PDFGRA (+) chronic eosinophilic leukemias.

Detection of the FIP1L1-PDGFRA fusion gene or the corresponding cryptic 4q12 deletion supports the diagnosis of chronic eosinophilic leukemia (CEL) in patients with chronic hypereosinophilia. We retrospectively characterized 17 patients fulfilling WHO criteria for idiopathic hypereosinophilic syndrome (IHES) or CEL, using nested RT-PCR and interphase fluorescence in situ hybridization (FISH). Eight had FIP1L1-PDGFRA (+) CEL, three had FIP1L1-PDGFRA (-) CEL and six had IHES. FIP1L1-PDGFRA (+) CEL responded poorly to steroids, hydroxyurea or interferon-alpha, and had a high probability of eosinophilic endomyocarditis (n=4) and disease-related death (n=4). In FIP1L1-PDGFRA (+) CEL, palpable splenomegaly was present in 5/8 cases, serum vitamin B(12) was always markedly increased, and marrow biopsies revealed a distinctively myeloproliferative aspect. Imatinib induced rapid complete hematological responses in 4/4 treated FIP1L1-PDGFRA (+) cases, including one female, and complete molecular remission in 2/3 evaluable cases. In the female patient, 1 log reduction of FIP1L1-PDGFRA copy number was reached as by real-time quantitative PCR (RQ-PCR). Thus, correlating IHES/CEL genotype with phenotype, FIP1L1-PDGFRA (+) CEL emerges as a homogeneous clinicobiological entity, where imatinib can induce molecular remission. While RT-PCR and interphase FISH are equally valid diagnostic tools, the role of marrow biopsy in diagnosis and of RQ-PCR in disease and therapy monitoring needs further evaluation.

Adult↗
PubMed2001

Itraconazole versus amphotericin B plus nystatin in the prophylaxis of fungal infections in neutropenic cancer patients.

The efficacy and safety of itraconazole oral solution and a combination of amphotericin B capsules plus nystatin oral suspension were compared in the prophylaxis of fungal infections in neutropenic patients. In an open, randomized, multicentre trial, 144 patients received itraconazole oral solution 100 mg bd, and 133 patients received amphotericin B 500 mg tds plus nystatin 2 MU qds. Overall, 65% of itraconazole-treated patients were considered to have had successful prophylaxis, compared with 53% in the polyene group. Proven deep fungal infections occurred in 5% of patients in each group. Fewer patients receiving itraconazole than amphotericin plus nystatin had superficial infections (3 versus 8%; P = 0.066). This trend in favour of itraconazole was seen in patients with profound neutropenia (neutrophil count <0.1 x 10(9) cells/L at least once) or prolonged neutropenia (neutrophil count <1.0 x 10(9) cells/L for >14 days). The median time to prophylactic failure was longer in the itraconazole group (37 days) than in the polyene group (34 days). The number of patients with fungal colonization (nose, sputum, stool) changed more favourably from baseline to endpoint in the itraconazole group than in the polyene group. Both treatments were safe and well tolerated; however, patients receiving amphotericin plus nystatin had a higher incidence of nausea and rash. In conclusion, itraconazole oral solution at doses of 100 mg bd and oral amphotericin B plus nystatin have similar prophylactic efficacy against fungal infections in neutropenic patients. On the basis of reduced incidence of superficial fungal infections, fungal colonization and specific adverse events, itraconazole may be the preferred treatment.

Adult↗
PubMed2000

Prognostic value of a new scoring system for hospital mortality in acute renal failure.

AIM AND METHODS: In order to define a prognostic scoring system for hospital mortality of individual patients with acute renal failure (ARF), data were collected prospectively in a single centre study (Stuivenberg General Hospital, Antwerp, Belgium) on 197 adult patients consecutively admitted to the intensive care unit (ICU) during one year. Mean age was 69.8 (+/- 14.7), male/female ratio was 118/79. RESULTS: Hospital mortality was 53%, 26% of the patients who were treated with renal replacement therapy. For developing the model all parameters showing a significant difference between survivors and non-survivors were entered in the multivariate analysis. Two SHARF scores (= Stuivenberg Hospital Acute Renal Failure scores) were developed, one at the time of diagnosis of ARF (T0) and the other 48 hours later (T48): SHARF T0 (7 x age) + (6 x alb0) + (3 x PTT0) + (39 x vent0) + (9 x heartf0) + 52 SHARF T48 (7 x age) + (6 x alb0) + (3 x PTT0) + (43 x vent48) + (16 x heartf48) + 52 age, albumin (alb0) and prothrombine time (PTT0) at T0 are expressed as categories, respiratory support (vent) and heart failure (heartf) at T0 and T48 are presented as absent (0) or present (1). In the linear regression model, r2 was, respectively, 0.36 and 0.43. The area under the receiver operator characteristic (ROC) curves, judging the discrimination ability between survivors and non-survivors, for T0 and T48 were, respectively, 0.87 and 0.90. The Hosmer-Lemeshow goodness-of-fit C statistic for T0 was C = 8.47; df8; p = 0.3 89 and for T48 C = 11.05; df = 8; p = 0.199. CONCLUSION: We conclude that this scoring system, developed for all types of ARF, compares favorably with published scores and can become useful as a bedside tool for predicting hospital mortality in individual patients. A second measuring point increased the predictive value of the model. The results have to be confirmed in an ongoing prospective multicentre study.

Acute Kidney Injury↗
PubMed1999

Mucormycosis in allogeneic bone marrow transplant recipients: report of five cases and review of the role of iron overload in the pathogenesis.

In a 10-year consecutive series of 263 allogeneic bone marrow transplant recipients, we identified five cases (1.9%) of invasive mucormycosis. Only one infection occurred within the first 100 days after transplantation, while the remainder complicated the late post-transplant course (median day of diagnosis: 343). Sites of infection were considered 'non-classical' and included pulmonary, cutaneous and gastric involvement. No case of fungal dissemination was observed. Mucormycosis was the primary cause of death in three of the five patients. Corticosteroid-treated graft-versus-host disease, either acute or chronic, or severe neutropenia were present in all cases. However, compared with a matched control population, the most striking finding was the demonstration of severe iron overload in each of the mucormycosis patients. The mean level of serum ferritin, transferrin saturation and number of transfused units of red cells (2029 microg/l, 92% and 52 units, respectively) in the study group is significantly higher compared with the control group (P < 0.05). The difference with other risk groups for mucormycosis, including deferoxamine-treated dialysis patients and acidotic diabetics, was analyzed in view of the possible pathogenic role of iron. Although these infections are often fatal, limited disease may have a better prognosis if diagnosed early and treated aggressively.

Adult↗
PubMed1999

Comparison of different routes of administration of nadroparin in hemodialysis.

AIM: In an open, crossover, randomized study in hemodialysis patients, we investigated possible differences of the effect of the low molecular weight heparin (LMWH) nadroparin/fraxiparine in relation to the route of administration. PATIENTS AND METHODS: The effect of nadroparin, administered by the venous line or by the arterial line after priming of the extracorporeal circuit with a part of the total dose administered, was compared with administration of the same dose by the arterial line as recommended by the manufacturer. Twelve stable, chronic hemodialysis patients were studied during 3 dialysis sessions for each treatment option. Concomitant medication was kept constant. RESULTS: Results obtained after administration of nadroparin by the venous line were comparable to those obtained after administration by the arterial line. When a part of the dose was added to the priming solution, the anti-Xa activity, measured after 2 hours of dialysis, was somewhat lower (p = 0.09). There was also a tendency towards longer manual compression time in this group. There was no difference in hemoglobin, serum urea and creatinine before the study and at the end of each treatment option. CONCLUSION: We therefore conclude that the safety and efficacy of administration of LMWH by the arterial and by the venous route are identical. There is no need for addition of a small dose of LMWH to the priming fluid.

Adult↗
PubMed1998

Patients with high-risk myelodysplastic syndrome can have polyclonal or clonal haemopoiesis in complete haematological remission.

The clonality of mature peripheral blood-derived myeloid and lymphoid cells and bone marrow haemopoietic progenitors from 18 females with myelodysplasia (MDS) (five refractory anaemia, RA; one RA with ringed sideroblasts, RARS; three chronic myelomonocytic leukaemia, CMML; four RA with excess of blasts, RAEB; five RAEB in transformation, RAEB-t) was studied by X-chromosome inactivation analysis. Using the human androgen-receptor (HUMARA) assay, we analysed the clonal patterns of highly purified immature CD34+ 38- and committed CD34+ 38+ marrow-derived progenitors, and CD16+ 14- granulocytes, CD14+ monocytes, CD3+ T and CD19+ B lymphocytes from peripheral blood. In high-risk patients (RAEB, RAEB-t), clonality analysis was performed before and after intensive remission-induction treatment. All patients, except one with RA, had predominance of a single clone in their granulocytes and monocytes. The same clonal pattern was found in CD34+ progenitor cells. In contrast, CD3+ T lymphocytes were polyclonal or oligoclonal in 14/18 patients. X-chromosome inactivation patterns of CD19+ B cells were highly concordant with CD3+ T cells except for two patients (one RA, one CMML) with monoclonal B and polyclonal T lymphocytes, therefore suggesting a clonal mutation in a progenitor common to the myeloid and B-lymphoid lineages or the coexistence of MDS and a B-cell disorder in these particular patients. After high-dose non-myeloablative chemotherapy, polyclonal haemopoiesis was reinstalled in the mature myeloid cells and immature and committed marrow progenitors in three of four patients achieving complete haematological remission. Therefore we conclude that most haematological remissions in MDS are associated with restoration of polyclonal haemopoiesis.

Adult↗
PubMed1997

A single course of remission reinduction chemotherapy for acute myelogenous leukemia relapsing after allogeneic bone marrow transplantation is complicated by graft-versus-host disease and followed by sustained complete remission.

Graft-versus-host disease (GVHD) remains a major immunological complication after allogeneic bone marrow transplantation (allo-BMT), but also favors development of the beneficial graft-versus-leukemia (GVL) effect. A patient with AML-M4 (inv (16)) is described, who was given non-myeloablative remission reinduction therapy for leukemic relapse (inv (16), trisomy 8) diagnosed on day 184 after HLA-compatible sibling BMT. On day 236, ie about 6 weeks after completion of this course, a clinical syndrome suggestive of acute GVHD grade 3 had developed. Skin biopsy confirmed the clinical diagnosis of GVHD, with a compatible liver biopsy. Transfusion-associated GVHD was ruled out by analysis of short tandem repeat (STR) alleles in the skin biopsy, revealing alleles from donor and recipient but not from third party origin. Cyclosporin A (CsA) therapy, which had been tapered between days 150 and 175, was resumed, resulting in a favorable response and gradual transition to limited chronic GVHD. The patient has since remained in complete remission with an excellent performance status for more than 40 months, without further chemotherapy. Thus this biopsy proven case of GVHD was induced by marrow donor lymphocytes more than 200 days after transplantation and apparently triggered by remission reinduction chemotherapy. The case indicates that intensive non-myeloablative chemotherapy can cure AML relapsing after allo-BMT. The therapeutic effect in this case probably involved a direct pharmacological suppression of the leukemic clone followed by a GVL effect initiated by donor-derived alloreactive T lymphocytes.

Acute Disease↗
PubMed1997

Autologous peripheral blood progenitor cell transplantation in patients with high-risk myelodysplastic syndromes.

Most patients with myelodysplastic syndromes (MDSs) who achieve a complete remission under aggressive chemotherapy develop a recurrence within 18 to 24 months. Autologous stem cell transplantation has therefore been suggested as a potential means of increasing treatment efficacy. As compared with bone marrow stem cell autografts, peripheral stem cell autografts have a higher harvesting yield and a shorter duration of aplasia after reinjection. Also, the results reported herein suggest that polyclonal stem cells harvested after chemotherapy-induced aplasia and growth factor therapy are capable of ensuring normal hematopoiesis and may provide prolonged remissions in some patients.

Adult↗
PubMed1996

Further evidence for the clonal nature of the idiopathic hypereosinophilic syndrome: complete haematological and cytogenetic remission induced by interferon-alpha in a case with a unique chromosomal abnormality.

A 49-year-old man with the idiopathic hypereosinophilic syndrome (HES) and a unique chromosomal abnormality 46,XY,t(5;9)(q32;q33) is reported. Complete cytogenetic remission was induced by interferon alpha-2b (IFN-alpha). The beneficial action of IFN-alpha in different stem-cell disorders such as CML, HES, multiple myeloma and solid tumours such as hypernephroma or malignant melanoma suggests a common regulatory effect possibly by immunomodulation or other (immune-mediated) mechanisms, but the exact pathophysiological mechanisms remain hypothetic and unresolved. Since it has been known for some years that the genes encoding for GM-CSF, IL-3 and IL-5 reside on the long arm of chromosome 5, it could be possible that the chromosomal translocation in our patient resulted in excess production of these cytokines, hence causing the hypereosinophilia. This case report and the results obtained from the literature review support the growing body of evidence that IFN-alpha has a major place in the long-term treatment of HES, especially in those cases resistant to conventional treatment, with cytogenetic abnormalities, or presenting as a myeloproliferative variant of HES. In those cases IFN-alpha results in lower morbidity, lower mortality and long-term survival.

Chromosomes, Human, Pair 5↗
PubMed1996

Imaging red blood cells with the atomic force microscope.

A novel technique for the reproduction of ultramorphological images and details of the surface of normal and pathological red blood cells (RBC) was investigated. The atomic force microscope (AFM) provided high-resolution images of cell surfaces. The RBC dimensions obtained by this technique revealed differences between native red cells in smears and glutaraldehyde-fixed red cells. It was shown that fixed red blood cells were best suited for the ultramorphological imaging of the cell surface.

Erythrocytes↗
PubMed1995

Polyclonal primitive hematopoietic progenitors can be detected in mobilized peripheral blood from patients with high-risk myelodysplastic syndromes.

Myelodysplastic syndromes (MDS) form a heterogeneous group of clonal hematopoietic disorders with unfavourable prognosis. Allogeneic bone marrow transplantation is the only potentially curative treatment, but remains limited to a small subgroup of younger patients with HLA-compatible donors. As autologous stem cell transplantation is currently being explored as an alternative treatment strategy for MDS, more information needs to be acquired regarding the clonal nature of the progenitor cells in these autografts. Therefore, we have analyzed the clonal patterns of highly purified hematopoietic progenitors and their mature daughter cells in mobilized peripheral blood collections produced from five female patients with high-risk MDS in complete hematologic remission. X-chromosome activation patterns of flow-sorted immature (CD34 + 38low, CD34 + 33low) and committed (CD34 + 38high, CD34 + 33high) progenitors were studied with the polymerase chain reaction-based HUMARA assay. In four patients, a polyclonal remission was shown in all stem cell subpopulations and their mature daughter cells whereas one patient was found to remain skewed in all fractions, except T lymphocytes. This study provides strong evidence that polyclonal immature hematopoietic progenitors can be mobilized and harvested in patients high-risk MDS after treatment with high-dose chemotherapy.

Adult↗
PubMed1995

Therapy-related acute myeloid leukemia with t(8;16)(p11;p13) following anthracycline-based therapy for nonmetastatic osteosarcoma.

A case of therapy-related AML with t(8;16)(p11;p13) 14 months following the end of anthracycline-containing chemotherapy for a nonmetastatic osteosarcoma of the left tibia is presented. The patient was successfully treated with intensive remission-induction chemotherapy. Subsequently, he underwent an uncomplicated allogeneic bone marrow transplantation from his HLA-identical brother and is at present alive and disease-free 10 months after diagnosis of the secondary AML.

Acute Disease↗
PubMed1995

Risks of rhG-CSF treatment in drug-induced agranulocytosis.

Nine patients with drug-induced agranulocytosis received recombinant human granulocyte colony-stimulating factor (rhG-CSF) to accelerate myeloid recovery because of life-threatening infections related to neutropenia. All patients showed a quick recovery of their granulocyte counts. Side effects were substantial, however. Three patients, two with a severe infection and one with preexisting pulmonary infiltrates, developed worsening of their respiratory status during neutrophil recovery, resulting in clinical manifestations of the adult respiratory distress syndrome (ARDS). In view of these major complications, the exact place of hematopoietic growth factors in the treatment of drug-induced agranulocytosis remains to be determined.

Adult↗