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C de Wolf-Peeters

Publications and source records attributed to C de Wolf-Peeters.

At least 19 recordsLinked to original sources
PubMed2004

Long-term efficacy of the CHVmP/BV regimen used for aggressive non-Hodgkin's lymphoma in three randomised EORTC trials.

We analysed data from 936 newly-diagnosed patients with advanced, aggressive non-Hodgkin's lymphoma (NHL) treated in three randomised European Organisation for Research and Treatment of Cancer (EORTC) trials performed between 1980 and 1999 (median follow-up of 8.7 (0.2-20.4) years). The CHOP-like regimen CHVmP/BV (cyclophosphamide, doxorubicin, teniposide and prednisone with bleomycin and vincristine at mid-interval), was compared with CHVmP (CHVmP/BV without bleomycin and vincristine), ProMACE-MOPP (methotrexate, doxorubicin, cyclophosphamide, etoposide, mechlorethamide, vincristine, procarbazine and prednisone) and CHVmp/BV with additional, autologous stem-cell transplantation, respectively. Overall, treatment with CHVmP/BV resulted in a better long-term outcome with 63% complete responses being observed and an overall survival (OS) of 59 and 43% at 5 and 10 years, respectively. Remarkably, OS after CHVmP/BV improved across the trials, even after stratifying for the International Prognostic Index (IPI). This finding could not be directly related to better salvage treatments during the last decade. Selection bias appears to be responsible: stepwise corrections for small differences in inclusion criteria eliminated the difference in OS, especially when histological subgroups were studied. This systemic review underlines the difficulties encountered in retrospective sub-set analyses and the biases that can be introduced when recent studies are compared with older ones.

Adolescent↗
PubMed2001

The NPM-ALK and the ATIC-ALK fusion genes can be detected in non-neoplastic cells.

Anaplastic large cell lymphoma (ALCL) is frequently associated with the t(2;5)(p23;q35) translocation. It creates a NPM-ALK fusion gene, fusing the anaplastic lymphoma kinase (ALK) gene (2p23) and the nucleophosmin (NPM) gene (5q35). Other rearrangements involving the ALK gene have recently been shown to be associated with ALCL, among which the ATIC-ALK rearrangement resulting from the inv(2)(p23q35) translocation is probably the most recurrent. The aims of the present study were to investigate the presence of NPM-ALK and ATIC-ALK fusion genes in ALCL, using a real-time 5' exonuclease-based reverse-transcription polymerase chain reaction (RT-PCR). This sensitive technique was also applied to investigate whether both fusion genes might be detected in Hodgkin's disease cases and in reactive lymphoid tissue. Results of the RT-PCR were compared to ALK immunostaining, cytogenetics, and fluorescence in situ hybridization (FISH) results. RT-PCR detected the NPM-ALK and ATIC-ALK fusions at high levels in 8 and 3 of a total of 13 ALK-positive ALCL cases. One ALK-positive ALCL case was negative for both fusion genes analyzed but revealed a new ALK-related translocation t(2;17)(p23;q25) by cytogenetic and FISH analysis. In addition, of the eight ALK-positive ALCL cases that were strongly positive for the NPM-ALK fusion, three cases also showed the presence of the ATIC-ALK fusion, although at much lower levels. Similarly, out of the three strongly positive ATIC-ALK cases, one case was positive for the NPM-ALK fusion, at low levels. Finally, the NPM-ALK and the ATIC-ALK fusions were detected, at equally low levels, respectively in 13 and 5 ALK-negative ALCL cases, in 11 and 5 Hodgkin's disease cases and in 20 and 1 non-neoplastic lymphoid tissues. The distinction between the high- and low-level detection was confirmed by relative quantitative RT-PCR for a representative number of cases. Of interest is the fact that the high-level detection coincided with the presence of ALK gene rearrangement detected by cytogenetics and FISH and may reflect a central role of the transcript in the oncogenic mechanism of ALK-positive ALCL. Low-level detection is not supported by cytogenetics and FISH, presumably due to the presence of the transcripts in only a small minority of normal cells not detectable by these techniques. Our findings demonstrate that NPM-ALK and ATIC-ALK fusion transcripts may be detected in conditions other than ALK-positive ALCL including reactive lymphoid tissues, although at low levels, suggesting the presence of the transcripts in normal (bystander) cells. Moreover, they suggest that the ALK gene rearrangement by itself might be insufficient to induce tumor formation. They further question the validity of quantitative real-time RT-PCR for monitoring minimal residual disease in ALCL. Finally, the newly identified translocation t(2;17)(p23;q25) can be added to the list of ALK gene rearrangements occurring in ALK-positive ALCL.

Anaplastic Lymphoma Kinase↗
PubMed2000

gammadelta T-cell lymphomas: a homogeneous entity?

gammadelta T-cells comprise an immunologically distinct lymphoid population, characterized by specific morphological, phenotypical and functional properties. Therefore it seems reasonable to speculate that neoplasms derived from this particular T-cell subset display distinct features. Indeed, the prototype gammadelta T-cell lymphoma, hepatosplenic T-cell lymphoma constitutes a unique clinicopathological entitity which is intimately associated with a gammadelta T-cell phenotype. However, gammadelta T-cell lymphomas have also been described in other extranodal sites where, unlike reactive gammadelta T-cells and hepatosplenic gammadelta T-cell lymphomas, they display an important morphological heterogeneity. Moreover, these nonhepatosplenic gammadelta T-cell lymphomas are essentially not that different from their alphabeta T-cell receptor for antigen (TCR)-expressing counterparts and thus may be incorporated in the established T-cell lymphoma subclasses. However, subtle differences regarding their histopathological appearance as well as their biological behaviour indicate that further studies to determine the exact significance of TCR expression are required. Such inquiries may contribute to the general understanding of T-cell lymphomagenesis in general, which is still obscure.

Animals↗
PubMed1999

Gene rearrangements in T-cell lymphoblastic lymphoma.

This study presents an examination of the Ig heavy chain (IgH) and T-cell receptor gamma (TCRgamma) genes in a series of 39 CD3-positive T-cell acute lymphoblastic leukaemia (ALL) cases with and without co-expression of CD79a; 30/39 cases had a rearrangement of the TCRgamma genes and two of these 30 cases also demonstrated an IgH rearrangement. No cases had solely an IgH rearrangement. The conclusion of the study is that lymphoblastic lymphoma cases that are positive for CD3 are of T-cell lineage, regardless of CD79a expression.

Adolescent↗
PubMed1997

Marginal zone B-cell lymphomas including mucosa-associated lymphoid tissue type lymphoma (MALT), monocytoid B-cell lymphoma and splenic marginal zone cell lymphoma and their relation to the reactive marginal zone.

The marginal zone of the B follicle represents a well-defined compartment of the B area. Its cellular composition is distinct from that of the follicle centre, from which it also differs in its functional role in the immune response. Several newly identified lymphoma entities, e.g. extranodal MALT type lymphoma, nodal monocytoid B-cell lymphoma and splenic marginal zone B-cell lymphoma, display in common a very peculiar organoid growth pattern reminiscent of the marginal zone. Moreover, their neoplastic components share morphologic and phenotypic similarities to the cellular components of the marginal zone. The clinical characteristics of these various marginal zone cell lymphomas may differ depending of the organ which is involved. Nevertheless, they all share common cytogenetic abnormalities suggesting a common pathogenesis.

Humans↗
PubMed1997

Expression of gelatinase B and the extracellular matrix metalloproteinase inducer EMMPRIN in benign and malignant pigment cell lesions of the skin.

By the degradative effect on basement membrane collagen type IV, matrix metalloproteinases (MMPs) or gelatinases are important in the early invasion of malignant tumors. These enzymes may be released by the tumor cells themselves or may be derived from nearby fibroblasts that have been stimulated by the extracellular MMP inducer EMMPRIN. We studied the distribution of 92-kd gelatinase B (MMP-9) and of EMMPRIN in 33 benign and 41 malignant, paraffin-embedded pigment cell lesions using immunohistochemistry and monoclonal antibodies. In benign pigment cell lesions, EMMPRIN but not gelatinase B was expressed in cellular blue nevi whereas all other benign lesions, including common blue nevi, were negative. In malignant melanomas (MMs), both gelatinase B and EMMPRIN were variably expressed in the pure and invasive radial growth phase but not in the vertical growth phase. All lentigo maligna cases and all metastatic lesions were negative. Of MMs with thickness < 1.6 mm, 63% expressed gelatinase B and 70% expressed EMMPRIN, whereas in MMs with > 1.6 mm thickness, only 10% expressed gelatinase B and only 25% expressed EMMPRIN. We conclude that early invasion of MM is associated with de novo expression of gelatinase B and EMMPRIN by neoplastic melanocytes. Expression of EMMPRIN and MMP-9 may be partly responsible for the stromal changes observed in thin MM. Their absence in the vertical growth phase and in metastatic lesions suggests that other factors are involved in tissue degradation during later stages of tumor progression in MM. The lack of both gelatinase B and EMMPRIN in lentigo maligna may contribute to the indolent behavior of this type of pigment cell lesion.

Antigens, CD↗
PubMed1996

Molecular characterization of the t(2;5) (p23; q35) translocation in anaplastic large cell lymphoma (Ki-1) and Hodgkin's disease.

The precise cellular origin and the pathogenetic mechanism(s) leading to the neoplastic transformation of anaplastic large cell lymphoma (ALCL) and the Reed-Sternberg cell of Hodgkin's disease (HD) remains largely uncertain. Classical cytogenetic analysis has shown a unique translocation involving bands 2p23 and 5q35 bands in a variable number of ALCLs. It has been recently shown that the nucleophosmin/B23 (NPM) gene (5q35) and a novel anaplastic lymphoma kinase (ALK; 2p23) are the fused genes of t(2;5). To investigate the presence and the precise frequency of NPM-ALK gene products among ALCL and HD cases, a large and well-characterized panel of ALCL (n = 49) and HD (n = 72) cases was studied using multiple strategies including reverse transcriptase-polymerase chain reaction (RT-PCR), Southern blot analysis, and immunohistochemistry. Overall, 6 (3 T and 3 null) of 49 ALCL and 3 (2 nodular sclerosis and 1 mixed cellularity) of 72 HD showed the presence of NPM-ALK transcripts by RT-PCR. NPM-ALK gene rearrangements were detected in all RT-PCR, NPM-ALK-positive ALCL by Southern blot analysis. Furthermore, in all the available cases we were able to show the presence of ALK-related protein using a specific polyclonal antiserum recognizing the cytoplasmic domain of ALK by immunohistochemistry. Our data show that NPM-ALK gene transcripts are identified in a subpopulation of ALCL, almost exclusively in T or null cell in origin, and in rare cases of HD. These findings show that some HD may be closely related to ALCL, giving us new insights on the pathogenesis and possibly biologic evolution of HD.

Anaplastic Lymphoma Kinase↗
PubMed1996

Trisomy 3 in marginal zone B-cell lymphoma: a study based on cytogenetic analysis and fluorescence in situ hybridization.

Trisomy 3 represents the most frequent and consistent chromosomal abnormality characterizing the recently defined entity marginal zone B-cell lymphoma (MZBCL). By cytogenetic analysis and/or fluorescence in situ hybridization (FISH) on interphase nuclei we found in increased copy number of chromosome 3 in 22/36 (61%) successfully analysed cases, including 8/12 cases with extranodal MZBCL, 8/13 cases with nodal MZBCL, and 6/11 patients with splenic MZBCL. Sensitivity of interphase cytogenetics was somewhat higher than that of conventional cytogenetic investigation. Structural chromosomal changes involving at least one chromosome 3 were seen in 11/20 cases with an increased copy number of chromosome 3: +de(3)(p13) was demonstrated in three cases, and was the sole chromosomal abnormality in one of them; +i(3)(q10) was seen in two other patients; and rearrangements involving various breakpoints on the long arm of chromosome 3 were found in the remaining cases. FISH on metaphase spreads confirmed these structural abnormalities and additionally showed two unexpected translocations involving chromosome 3. We conclude that: (1) trisomy 3 occurs in a high proportion of extranodal, nodal and splenic MZBCL; (2) FISH on interphase nuclei is an additional and sensitive tool in detecting an increased copy number of chromosome 3 in MZBCL; (3) additional structural abnormalities involving the long arm of chromosome 3 are frequent but non-recurrent and are perhaps secondary changes; and (4) abnormalities such as +del(3)(pl3) and +i(3)(q10) suggest that genes located on the long arm of chromosome 3 are of particular importance in the pathogenesis of MZBCL.

Adult↗
PubMed1995

Mantle cell lymphoma: a clinicopathological study of 55 cases.

A recently described unifying proposal for mantle cell lymphoma has led to the formulation of strict diagnostic criteria based on morphology, immunology and molecular data to define this specific entity. Previous studies were often based on broader definitions such as centrocytic lymphoma, intermediately differentiated lymphoma or mantle zone lymphoma and, therefore, included a variety of entities with some, but not all, features ascribed to the mantle cell lymphoma. Since the publication of the unifying proposal no comprehensive studies have been published to confirm and support it. We selected 55 cases of mantle cell lymphoma collected in our institution in order to evaluate the validity of the proposal and, by using strict criteria, we analysed the morphological features, their variations and the changes occurring in the course of the disease as well as its clinical behaviour. The analysis of this material demonstrates that mantle cell lymphoma affects predominantly elderly males presenting with an advanced stage of disease. Twenty-four out of 55 patients died with, or of, the disease with a median survival of 32 months, even though most of them received aggressive chemotherapy. In all cases the histological features were strikingly uniform and most cases had a diffuse growth pattern. The neoplastic cells corresponded to small cleaved cells with a minimal variation in shape and size from one case to the other. The phenotype of the neoplastic cells was remarkably constant with expression of several pan-B cell markers, IgM, IgD and CD5, and lack of CD10 and CD23.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Epithelium-lining macrophages in psoriasis.

Epithelium-lining macrophages are spindle-shaped cells which line the epidermis and hair follicles. We studied the distribution and phenotype of this hitherto neglected member of the dermal monocyte/macrophage system in 25 lesional psoriatic, and five normal skin biopsies. Epithelium-lining macrophages were inconspicuous in normal skin, whereas their number was increased in almost two-thirds of psoriatic cases; in nine out of 25 lesional skin biopsies, these flattened cells formed an almost continuous single-cell row at the dermo-epidermal junction. Immunophenotyping revealed that these cells expressed the leucocyte common antigen CD45, and the macrophage markers CD14, CD36 and CD4, but not CD11b. Epithelium-lining macrophages strongly expressed HLA-DR-antigens and CD11a, but lacked the Langerhans cell marker CD1, and CD34. The dermal dendrocyte marker factor XIIIa was expressed in only a minority of these cells. It is concluded that epithelium-lining macrophages represent a separate subset of dermal monocytes/macrophages with a distinct tissue localization and immunophenotype. Their restricted distribution and close association with the epidermis may suggest a role in the regulation of epidermal growth. Alternatively, the expression of several immune-associated molecules may indicate that epithelium-lining macrophages are involved in the antigen-dependent or -independent activation of T cells.

Antigens, CD↗
PubMed1991

Cytogenetic characterization of three cases of unusual B-cell non-Hodgkin's lymphoma.

We report the cytogenetic results in three cases of B-cell non-Hodgkin's lymphomas with morphologic and immunophenotypic features compatible with a non-follicle center cell lymphoma. In all cases, a chromosome breakpoint at 14q32 and structural abnormalities of 1p were found. Increased copies of chromosome segment 12q and structural rearrangements of chromosome 6 were found in two cases. Translocation (14;18)(q32;q21) with rearrangement of bcl-2 was found in one case. These lymphomas have a perifollicular growth pattern and IgM+, IgD+, CD10-, and CD22+ immunophenotype features typical of non-follicle center cell lymphomas and probably belong to the follicle mantle lymphomas described recently. Little cytogenetic data about this group of lymphomas is available, possibly because in the Working Formulation for the Classification of Lymphomas they are not separated from follicle center cell lymphomas.

Adult↗
PubMed1991

Low-dose total body irradiation versus combination chemotherapy for lymphomas with follicular growth pattern.

The treatment of Non-Hodgkin's lymphomas with follicular growth pattern and advanced stage of disease remains controversial. Treatments varying from no initial treatment up to aggressive combination chemotherapy have been advocated. The EORTC Lymphoma Cooperative Group has performed a randomized prospective trial comparing short duration low dose total body irradiation (TBI) vs combination chemotherapy (CHVmP) + consolidation radiotherapy. Ninety-three patients were entered; of 84 evaluable patients, 44 received TBI and 40 CHVmP. Complete remission (CR) rates were 36%--TBI and 55%--CHVmP, but overall response rates were identical, 76 versus 69%. No significant difference in freedom from progression or survival was observed. No unexpected toxicity was seen. Although numbers are small, we cannot conclude that aggressive combination chemo-radiotherapy resulted in a better survival. Our analysis confirms that there is a constant risk of relapse. Other approaches should be explored if survival benefit is the ultimate goal in treatment of this patient population.

Adolescent↗
PubMed1991

Superiority of second over first generation chemotherapy in a randomized trial for stage III-IV intermediate and high-grade non-Hodgkin's lymphoma (NHL): the 1980-1985 EORTC trial. The EORTC Lymphoma Group.

A first-generation CHOP-like cyclic combination chemotherapy (CT) regimen using cyclophosphamide 600 mg/m2 IV d1, hydroxorubicin (doxorubicin) 50 mg/m2 IV d1, VM26 60 mg/m2 IV d1, and prednisone 40 mg/m2 PO d1-5 (CHVmP) was compared to a second-generation combination wherein vincristine 1.4 mg/m2 IV and bleomycin 6 mg/m2 IM/IV were added at mid-interval (d15) to the former drugs (CHVmP + VB) in the treatment of intermediate- and high-grade malignant NHL. From April 1980 to January 1986, 141 eligible patients with stage III-IV unfavorable histologies (except T lymphoblastic NHL) entered this EORTC randomized trial. In both arms adjuvant radiotherapy (30 Gy) was given in instances of bulky or residual disease. In all patient subsets the outcome favored the second-generation regimen. The difference was even greater in patients with Diffuse Large Cell Lymphoma (DLCL). At 5 years, overall survival was 53% with CHVmP + VB versus 29% (p = 0.002). The advantage was due to a higher complete remission (CR) rate (80% versus 50%, p = 0.01). Indeed, once CR was achieved the relapse-free survival (RFS) was not significantly influenced (59% versus 49%). No significant additional toxicity could be attributed to vincristine and bleomycin. This study demonstrates a clear benefit for intermediate- and high-risk malignant NHL and particularly DLCL from intercalating non-myelotoxic drugs at mid-cycle intervals, without adverse effects.

Adolescent↗
PubMed1990

Differential expression of the calcium-binding proteins MRP8 and MRP14 in granulomatous conditions: an immunohistochemical study.

MRP14 and MRP8 are well-characterized calcium-binding proteins present in myeloid cells and mononuclear phagocytes. These antigens can easily be visualized in paraffin-embedded tissue, making use of monospecific polyclonal antibodies. This study evaluates MRP14 and MRP8 expression in mononuclear phagocytes in various granulomatous conditions. MRP14 is strongly expressed in all granulomatous conditions. MRP8 is variably expressed. Mononuclear phagocytes in granulomas of foreign body type, cat-scratch disease and erythema nodosum strongly express MRP8. In contrast, MRP8 expression is weak or absent in mononuclear phagocytes of sarcoidosis and tuberculosis. These results show differences in immunophenotype between non-phagocytic mononuclear phagocytes in delayed hypersensitivity type granulomas and phagocytic mononuclear phagocytes in non-hypersensitivity and non-immunological granulomas.

Calcium-Binding Proteins↗
PubMed1989

Anti-high endothelial venule monoclonal antibody HECA-452 recognizes plasmacytoid T cells and delineates an "extranodular" compartment in the reactive lymph node.

So-called plasmacytoid T cells represent a subset of monocyte related cells, which share with endothelium the CD36+ CD11b- (OKM5+ OKM1-) phenotype. The reactivity of plasmacytoid T cells with rat monoclonal antibody HECA-452, highly specific for high endothelial venules, was analyzed in reactive lymph nodes. In all cases, HECA-452 not only labelled the endothelium of high endothelial venules, but also strongly reacted with singular and clustered plasmacytoid T cells. The HECA-452 positivity for high endothelial venules and plasmacytoid T cells visualized a lymph node compartment extending from the subcapsular sinus to the corticomedullary junction. This compartment surrounded the composite nodule and was designated the "extranodular" compartment. The co-occurrence of plasmacytoid T cells and high endothelial venules in this extranodular compartment, together with their immunophenotypical similarities, may be indicative of functional co-operations.

Antibodies, Monoclonal↗
PubMed1989

Plasmacytoid monocytes (so-called plasmacytoid T-cells) in Kikuchi's lymphadenitis. An immunohistologic study.

Three cases of Kikuchi's lymphadenitis were studied immunohistochemically on paraffin-embedded material in order to compare the plasmacytoid monocyte aggregates occurring in this disorder with plasmacytoid monocyte clusters in nonspecific reactive lymphadenitis. One of the cases was also analyzed on frozen material. In Kikuchi's lymphadenitis, plasmacytoid monocytes expressed the CD38 and LN1 antigens in addition to their monocyte/macrophage antigens found in nonspecific reactive lymph nodes. These plasmacytoid monocyte aggregates contained large numbers of Mac387+ lysozyme+ macrophages, scattered HLADR+ dendritic cells, and high numbers of CD8+ T-lymphocytes. Collections of T-immunoblasts or areas of necrosis were observed within these aggregates. The authors speculate that the histologic feature of Kikuchi's lymphadenitis is the morphologic substrate of a T-cell-mediated cytotoxic immune reaction occurring in plasmacytoid monocyte aggregates and resulting in plasmacytoid monocyte damage and necrosis.

Adult↗