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F Bauters

Publications and source records attributed to F Bauters.

At least 55 records · Page 3Linked to original sources

Autologous stem-cell transplantation for non-Hodgkin's lymphomas: the role of graft purging and radiotherapy posttransplantation--results of a retrospective analysis on 120 patients autografted in a single institution.

PURPOSE: To analyze retrospectively survival and prognostic factors of patients with non-Hodgkin's lymphoma (NHL) autografted from 1979 to 1995 in a single institution. PATIENTS AND METHODS: A total of 120 patients, 64 with aggressive and 56 with low-grade NHL, were autografted. The carmustine (BCNU), etoposide, cytarabine, and melphalan (BEAM) regimen was used in 104. The autograft was marrow in 101 patients. Marrow was purged in vitro by mafosfamide for 63 patients (adjusted dose [AD] in 32; unique dose [UD] in 31); 27 patients received a CD34+-selected graft. Following intensification, 45 patients received additional radiotherapy on previous sites of involvement. RESULTS: Outcome at 5 years for patients transplanted with low-grade NHL in first complete remission (CR1), in first partial remission (PR1), and in second complete remission (CR2) or beyond showed an event-free survival (EFS) of 75% +/- 12%, 46% +/- 18%, and 57% +/- 24%, a relapse incidence (RI) of 21% +/- 12%, 49% +/- 19%, and 43% +/- 25%, and a transplant-related mortality (TRM) of 5% +/- 5%, 10% +/- 7%, and 0%, respectively. For patients with aggressive NHL transplanted in CR1, in PR1, in CR2 or beyond, and in resistant relapse or in primary refractory disease, the EFS was of 73% +/- 9%, 58% +/- 19%, 29% +/- 16%, and 10% +/- 9%, the RI 22% +/- 9%, 14% +/- 9%, 77% +/- 18%, and 66% +/- 20%, and the TRM 6% +/- 6%, 32% +/- 21%, 11% +/- 10%, and 71% +/- 22%, respectively. In patients autografted upfront in first remission, additional radiotherapy was associated with a higher EFS, in univariate (P = .03) and multivariate analysis (P = .02, relative risk [RR] = .021). The role of graft purging with mafosfamide on the outcome reflected by the dose of colony-forming unit-granulocyte-macrophage (CFU-GM) per kilogram infused postpurging was assessed by univariate analysis: patients in first remission who received lower doses of CFU-GM had a lower RI and a higher EFS. CONCLUSION: This retrospective analysis suggests that marrow purging and posttransplant radiotherapy improve the outcome of patients with NHL autografted in first remission.

Adult↗

Several cytogenetic subclones may be identified within plasma cells from patients with monoclonal gammopathy of undetermined significance, both at diagnosis and during the indolent course of this condition.

Monoclonal gammopathy of undetermined significance (MGUS) is a frequent condition in patients over 50 years old, that ultimately leads to multiple myeloma (MM) in 20% of patients after 20 to 35 years of follow-up. Little is known about cytogenetic changes associated with this condition. We studied 19 MGUS patients both at diagnosis and after 12 to 35 months of follow-up (mean = 26), using DNA content measurement of bone marrow plasma cells (BMPC), and a new interphase fluorescence in situ hybridization technique (FISH) allowing the simultaneous identification of monotypic BMPC (fluorescent anti light-chain antibodies) and the determination of the number of copies for two different chromosomes within the same PC nucleus (one biotin-labeled probe coupled next to texas red avidin and one FITC-labeled probe). At diagnosis of the MGUS, single interphase FISH showed at least one numeric chromosome change in 13 of 19 patients, after the use of centromeric probes directed against chromosomes no. 3, no. 7, no. 9, and no. 11. At follow-up, abnormalities found at diagnosis in 13 patients were still shown. Moreover, abnormalities occurred in three of the last six patients (trisomy for one to three different chromosomes), although no patient evolved into MM. Dual interphase FISH showed that some BMPC bore numeric changes with both probes tested whereas other BMPC bore abnormality with only one of the probes tested. In patients who showed trisomy for at least three different chromosomes, distribution of numeric changes within BMPC defined significant numbers of up to seven different BMPC clones. All these various clones were shown both at diagnosis and at follow-up. In every patient, these various clones differed only for the number of abnormalities they exhibited, and could be related to each other in a model of gradual acquisition of chromosome changes. Eventually, data reported here show that MGUS patients acquire slowly, gradually, but ineluctably chromosome changes, distributed within several related subclones. However, these changes are not related to transformation into MM: among the various clones coexisting within the same patient, a peculiar change, still to demonstrate, might develop and lead to overt MM.

Adult↗

[Tuberculosis, mycobacterium infection and hairy cell leukemia].

OBJECTIVES: Diagnosis of tuberculosis and/or mycobacteria infection is particularly difficult in immunocompromised patients. PATIENTS AND METHODS: We examined the clinical presentation, means of diagnosis, treatment and outcome of tuberculosis in a retrospective study of 6 patients among 75 with hairy cell leukemia diagnosed from 1982 to 1995. RESULTS: Hearlding symptoms of tuberculosis diagnosis were: fever (6/6), weight loss (4/6), pleural effusion (1/6), superficial adenopathy (1/6), persistence of cytopenia or splenomegaly during the treatment of hairy cell leukemia. Pulmonary symptoms were present in only two cases. Diagnosis was obtained by positive culture of mycobacteria in 2 cases (Mycobacterium tuberculosis in pleural effusion, Mycobacterium kansaii in adenopathy). Microbiological diagnosis was never obtained from sputum (6/6). Diagnosis was obtained by histopathology in all cases: from bone marrow (2 cases), lymph nodes (2 cases), liver (1 case), spleen (1 case), umbilical fat (1 case). Tuberculosis was disseminated in all cases. By clinical, biological, microbiological histopathological means and response to treatment, tuberculosis was considered as: hematopoietic in all cases, hepatic (in 4/6), pleural (1/6), pulmonary (1/6). A favorable outcome of tuberculosis was observed in all cases. No death was observed. CONCLUSIONS: Tuberculosis was found in 8% of hair cell leukemia patients. In hairy cell leukemia, tuberculosis is characterized by few pulmonary symptoms and scarse microbiological documentation. In contrast, histopathology is very interesting to confirm diagnosis. Tuberculosis is in most cases disseminated and in particular hematopoietic diffusions is always present. In spite of existensive localization, the prognosis remains excellent and all patients can be cured. In our opinion, this good prognosis may be linked to the improvement of hairy cell leukemia treatment observed since the advent of interferon pentostatin and 2cdA.

Adult↗

[POEMS syndrome].

POEMS syndrome is an acronym defined by Bardwick (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal component and Skin changes). Other various clinical and biological features are reported: edema, cachexia, microangiopathic glomerulopathy, most rarely pulmonary hypertension, cutaneous necrosis. Thrombocytosis or polycythemia may be a prominent feature. POEMS syndrome is sometimes associated with lymphoproliferative disorder. Castelman-like disease is frequently observed as pathologic findings on lymph nodes. Distinction between POEMS syndrome and osteosclerotic myeloma is delicate. The rate of the monoclonal protein is modest-always less than 30 g/L-and is almost of the lambda light chain class. In contrast to multiple myeloma this syndrome is rarely associated with hypercalcemia, skeletal fracture, renal involvement and increasing of M component during evolution. Bone marrow plasmocytosis is usually less than 15% and the kinetic phenotype and genetic characteristics of the plasma cell remain those found in monoclonal gammopathy of undetermined significance. The pathophysiology of this syndrome remains largely unknown but overproduction of pro-inflammatory cytokines are reported, especially TNF alpha, IL-6 and IL-1 beta. Some clinical manifestations seem to be cytokine related. Polyneuropathy and cachexia are the main cause of death. A part corticosteroid and cure of solitary bone lesion, treatment is disappointing and survival is 60% at five years.

Humans↗

POEMS syndrome: report on six patients with unusual clinical signs, elevated levels of cytokines, macrophage involvement and chromosomal aberrations of bone marrow plasma cells.

POEMS syndrome is a multisystemic disorder characterized by the association of polyneuropathy, organomegaly, endocrinopathy, M protein, skin changes and various other systemic clinical signs. The pathophysiology of this syndrome remains largely unknown. In order to gain insight into its pathophysiology, we studied the clinical characteristics and performed serum analysis (auto-antibodies, cytokine levels) and phenotypic and cytogenetic studies of bone marrow plasma cells (BMPC) in six patients with unequivocal POEMS syndrome. Two unusual clinical signs were present in these patients: pulmonary hypertension (two patients) and diffuse cutaneous necrosis (one patient). No auto-antibodies against peripheral nerve (PN) antigens (SGPG and SGLPG glycolipids, GM1, GD1a, GD1b and GT1b gangliosides) were found. Sequential evaluations of serum cytokines (IL-1-beta, IL-6 and TNF-alpha) showed a moderate to marked elevations of IL-6 and TNF-alpha in all patients (up to six-fold for TNF-alpha and 16-fold for IL-6). Using in situ hybridization of these cytokines mRNAs on lymph node specimens of two patients who had an angiofollicular lymph node hyperplasia, a strong positivity was found with the IL-1-beta antisense probe in lymph node macrophages. On skin biopsy a high number of cells expressing TNF-alpha mRNA was observed in the dermis. The biological features of BMPC: phenotype (expression of CD19 and CD56 antigens), kinetics (Ki-67 index), karyotype, DNA content and chromosomal in situ hybridization remained those of BMPC found in monoclonal gammopathy of undetermined significance. We conclude that POEMS syndrome is a hypercytokinemic syndrome in which BMPC are not of malignant type. Macrophages are involved in this syndrome and their role has to be further investigated as well as treatments which act through an anti-cytokine mechanism.

Adult↗

Long-term follow-up of de novo myelodysplastic syndromes treated with intensive chemotherapy: incidence of long-term survivors and outcome of partial responders.

The percentage of long-term survivors after intensive chemotherapy and the outcome of MDS patients who achieve partial remission (PR) with intensive chemotherapy (IC) are not known. Between 1981 and 1996 we treated 99 patients with de novo MDS who had high-risk MDS or progression to AML, with IC. 41 (41%) achieved CR, 16 (16%) achieved partial remission (PR), 26 (26%) had failure, and 16 (16%) died in aplasia. Eight of the patients who achieved CR were autografted, three were allografted and the remaining cases received moderate consolidation chemotherapy. After IC, the 16 PR patients fulfilled the criteria for RA in 15 cases and CMML in one case. Median PR duration was 17 months, and three PR were > 3 years (39, 50+, 82+ months). Median actuarial survival of patients who achieved PR and CR was 18 months and 20 months from the onset of IC, respectively (difference not significant). Of the 71 patients treated before 1993, with sufficient follow-up, 10 (14%) had survived > 4 years (long-term survivors). Four of them were alive in first CR after 49+ to 110+ months and probably cured, two were alive in PR after 50+ and 82+ months and four had died after 49-78 months. Long-term survivors were characterized by a significantly higher incidence of RAEB-T at diagnosis, and with normal or favourable cytogenetic findings. In patients with RAEB-T at diagnosis included before 1993, 8/23 (35%) cases who had no unfavourable karyotype had survived > 4 years. Our findings suggest that MDS patients who achieve PR with IC, and not only those who achieve CR, can benefit from this type of treatment. The percentage of long-term survivors remains low, however, and is almost restricted to patients with RAEB-T at diagnosis and no unfavourable karyotype.

Adolescent↗

[Diagnosis of adenopathies and retroperitoneal masses by surgical endoscopy. Apropos of 93 cases].

Lumboscopy is an endoscopic surgical technique providing direct visualization of the retroperitoneal space from the kidney hilium to the iliac bifurcation. We report our 10-year experience with this technique used to diagnose masses in the retroperitoneal space. This method is not very invasive and the morbidity is low. The sensitivity is greater than needle biopsy under CT guidance.

Adolescent↗

Involvement of peripheral blood cells in multiple myeloma: chromosome changes are the rule within circulating plasma cells but not within B lymphocytes.

The mononuclear cells in the peripheral blood are implicated in the myeloma process especially with the presence of peripheral blood plasma cells (PBPC) and clonal B lymphocytes found using phenotypic or gene rearrangement techniques. The purpose of this study was to look for aneuploidy in the two main B cell components of the peripheral blood: PBPC and CD20-positive B lymphocytes. Conventional cytogenetics (CC) or DNA content analysis and fluorescence in situ hybridization (FISH) with centromeric probes were performed on bone marrow plasma cells (BMPC) of 21 patients with multiple myeloma and peripheral blood cells were studied as follows: immunostaining to look for PBPC and to assess their number, image analysis cytometry for the determination of their DNA content, and FISH chromosomes analysis. FISH was performed using probes against the chromsomes that were lost or gained in BMPC and was coupled with immunostaining of the relevant light chain or CD20 antigen to study PBPC or B lymphocytes, respectively. Monotypic PBPC were found in 16 patients. Their DNA content was the same or nearly the same as for BMPC and they exhibited the same monosomies or trisomies as those found within their BM counterpart. By contrast, DNA content of mononuclear cells other than PBPC was within normal ranges, and in 13 of 15 patients CD20-positive B lymphocytes failed to show chromosomal changes by FISH analysis. In two patients however, a few CD20+ cells with lymphoid morphology exhibited chromosome changes, hypothesizing that a few cytogenetically abnormal B cells without plasmocytic morphology may circulate. From these data, we conclude that PBPC share the same genetic abnormalities as BMPC and thus belong to the malignant clone, whereas most peripheral blood B lymphocytes are unrelated to the tumor clone.

Aged↗

Retroperitoneoscopy for the diagnosis of infiltrating retroperitoneal lymphadenopathy and masses.

BACKGROUND: Retroperitoneoscopy (RPS) is a form of direct vision endoscopy, used to explore the retroperitoneal space, and was first described by Bartel in 1969. METHODS: RPS was performed prospectively to diagnose infiltrating retroperitoneal lymphadenopathy or masses when needle aspiration biopsy under computed tomographic guidance (NABCT) failed to establish a definite diagnosis. RESULTS: From May 1985 to August 1995, RPS was performed in 118 patients (121 procedures). Mean hospital stay was 2.4 (range 2-5) days. The peroperative and perioperative morbidity rate was 6.6 per cent of the procedures. A precise diagnosis was obtained in 108 of the 118 patients. The sensitivity was 84 per cent for malignant lymphoma, 94 per cent for Hodgkin's lymphoma, 95 per cent for metastatic lymph nodes of carcinomas and 100 per cent for primary retroperitoneal tumours. The overall sensitivity was 91.5 per cent. CONCLUSION: RPS is an alternative procedure to NABCT when aspiration biopsy is not technically feasible because a lesion is too small to sample or failed to establish a precise histopathological diagnosis.

Adolescent↗

Prognostic factors in agnogenic myeloid metaplasia: a report on 195 cases with a new scoring system.

We studied the survival of 195 patients with agnogenic myeloid metaplasia (AMM) diagnosed between 1962 and 1992 in an attempt to stratify patients into risk groups. Median survival was 42 months. Adverse prognostic factors for survival were age > 60 years, hepatomegaly, weight loss, low hemoglobin level (Hb), low or very high leukocyte count (WBC), high percentage of circulating blasts, male sex, and low platelet count. A new scoring system based on two adverse prognostic factors, namely Hb < 10 g/dL and WBC < 4 or > 30 x 10(9)/L, was able to separate patients in three groups with low (0 factor), intermediate (1 factor), and high (2 factors) risks, associated with a median survival of 93, 26, and 13 months, respectively. An abnormal karyotype (32 cases of 94 tested patients) was associated with a short survival, especially in the low-risk group (median survival of 50 v 112 months in patients with normal karyotype). The prognostic factors for acute conversion were WBC > 30 x 10(9)/L and abnormal karyotype. Thus, hemoglobin level and leukocyte count provide a simple prognostic model for survival in AMM, and the adverse prognostic value of abnormal karyotype may be related to a higher rate of acute conversion.

Adult↗

Prognostic factors in myelodysplastic syndromes: critical analysis of the impact of age and gender and failure to identify a very-low-risk group using standard mortality ratio techniques.

We studied the prognostic value of age and gender by survival, and by standard mortality ratio (SMR) analyses, in 203 untreated patients with myelodysplastic syndromes (MDS); 57 refractory anaemia (RA), 23 refractory anaemia with ringed sideroblasts, 41 refractory anaemia with excess blasts (RAEB), 3 RAEB in transformation (RAEB-T) and 79 chronic myelomonocytic leukaemia (CMML), aged 23-89 years (median 69, M/F 0.5), who were all karyotyped. Median survival was 36 months. Adverse prognostic factors were: high bone-marrow blast percentage, complex karyotype, low platelet count, age > 60 years, low or high WBC count, haemoglobin < 10 g/dl, male gender. However, the standard mortality ratio (i.e. mortality compared to that of an age- and sex-adjusted population) was not different between male and female patients. Patients < 60 had a higher SMR than older patients. Therefore the prognostic values of age and gender for survival in MDS patients may reflect, at least in part, a characteristic of the population. Furthermore, even in low-risk groups defined by scoring system we were unable to define a subgroup of patients with a mortality similar to that of the normal population, especially in MDS patients aged < 60.

Adult↗

Low incidence of specific anti-platelet antibodies detected by the MAIPA assay in the serum of thrombocytopenic MDS patients and lack of correlation between platelet autoantibodies, platelet lifespan and response to danazol therapy.

We prospectively studied the mechanism of thrombocytopenia in 30 patients with myelodysplastic syndrome (MDS), who had a platelet count <or= 70 x 10(9)/l, and marrows blasts <or= 10% by analysis of platelet lifespan, platelet-bound IgG antibodies by platelet radioactive antiglobulin test (PRAT), and circulating and platelet-bound autoantibodies specifically directed against platelet glycoproteins by indirect and direct MAIPA test. PRAT analysis was positive in 21/30 patients (70%), but antiplatelet antibodies were found in only eight by the MAIPA test. Platelet lifespan was shortened in five cases, only one of whom had a positive MAIPA test. Patients were treated by danazol (600 mg/d), and 9/26 evaluable patients (35%) responded, including three of the five patients with shortened platelet lifespan. No correlation between platelet lifespan, results of PRAT and MAIPA tests, and response to danazol was found. In conclusion, specific antiplatelet autoantibodies, reduced platelet lifespan, and efficacy of androgen therapy on platelets were seen in 20%, 17% and 35% of MDS with thrombocytopenia, respectively, but no correlation between these findings was found in this study.

Adolescent↗

Transfer of p16inka/CDKN2 gene in leukaemic cell lines inhibits cell proliferation.

The gene encoding for p16ink4a, a negative regulator of transition between G1 and S phase, is homozygously deleted in a large proportion of acute lymphoblastic leukaemias (ALL). Transfer of p16ink4a gene in several solid tumour cell lines with functional pRb and lacking both p16ink4a alleles has resulted in a dramatic reduction of cell proliferation, and the aim of this work was to confirm this effect in leukaemic (especially ALL) cell lines. We tested the proliferation in liquid medium and in soft agar after transfer of p16ink4a gene by a retroviral vector in leukaemic cell lines with homozygous p16ink4a gene deletion (K562, CEM, Jurkat cell lines) or with p16ink4a gene hemizygous deletion and a point mutation inactivating the remaining allele (HL60 cell line). The viral titre obtained after transfection of PA317 amphotropic packaging cell line, which has a p16ink4a gene homozygous deletion, was low, suggesting that p16ink4a gene expression could impair viral production of retroviral packaging cell lines derived from the NIH3T3 cell line. After retroviral transfer of p16ink4a in cell lines and G418 selection in liquid medium, a strong cell proliferation inhibition was observed for K562, CEM and Jurkat, but no inhibition was seen for HL60. A strong growth reduction in soft agar was also observed with p16ink4a-transduced CEM, Jurkat and K562 cells, with a moderate growth reduction in the HL60 cell line. The growth inhibition in liquid culture, of K562 and Jurkat cell lines, was confirmed by electroporation transfer of the p16ink4a gene. Our findings show that p16ink4a gene transfer has a growth-inhibitory effect in leukaemic cell lines with p16ink4a gene homozygous deletion. These data suggest that p16 could be a suitable gene for gene therapy in ALL.

Cell Division↗