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1.
Oncogene ; 8(11): 3073-80, 1993 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-8414508

RESUMO

Two rearrangements affecting the same allele of the BCL2 gene were characterized by molecular analysis of an untreated follicular lymphoma. The first rearrangement interested the major breakpoint region (mbr) on chromosome 18 and a JH segment on chromosome 14. The other one was located at the 5' end of the BCL2 gene, in the so called variant cluster region (vcr), and consisted of a series of deletions that removed part of a DNA region where initiation of transcription normally occurs. Interestingly, both rearrangements involved the same BCL2 allele. The simultaneous presence of mbr (or mcr) translocations and of minor rearrangements in vcr has been previously suggested by restriction map analysis in a significant number of follicular lymphomas. The significance of these abnormalities on the oncogenic process is discussed.


Assuntos
Deleção de Genes , Rearranjo Gênico , Linfoma Folicular/genética , Oncogenes , Proteínas Proto-Oncogênicas/genética , Translocação Genética , Alelos , Sequência de Bases , Humanos , Dados de Sequência Molecular , Proteínas Proto-Oncogênicas c-bcl-2
2.
J Clin Oncol ; 10(7): 1078-85, 1992 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-1607914

RESUMO

PURPOSE: We analyzed prognostic factors in 80 adult patients with lymphoblastic lymphoma (LBL). PATIENTS AND METHODS: Twenty-one patients received six monthly courses of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) and maintenance chemotherapy for 12 months. The LNH-84 protocol (30 patients) consisted of four courses of high-dose CHOP followed by consolidation for 4 months. Both FRALLE (22 patients) and LALA (seven patients) protocols were two intensive chemotherapy regimens for acute lymphoblastic leukemia (ALL) that included an induction with daunorubicin, vincristine, cyclophosphamide, prednisolone (and asparaginase for the FRALLE regimen), consolidation, and maintenance chemotherapy that lasted for 2 years. RESULTS: Sixty-six patients (82%) achieved a complete remission (CR). The CR duration rate and overall survival rate at 30 months were estimated to be 46% and 51%, respectively, with a median follow-up of 55 months. Only two of 37 relapses occurred after 26 months. Chemotherapy protocol did not influence CR rate, CR duration, and survival. A higher CR rate was associated with an age of less than 40 years, lactic dehydrogenase (LDH) level of less than two times the upper limits of normal, and no or one extranodal site of disease. Short survival was associated with a failure to achieve CR, age older than 40 years, B symptoms, LDH level more than two times the upper limits of normal, and hemoglobin level of less than 100 g/L. Bone marrow involvement had no prognostic value. We could not evaluate precisely the prognostic value of Ann Arbor stage because inclusion criteria differed among treatment groups. CONCLUSION: Our findings suggest that age and LDH are two important pretreatment prognostic factors for adult LBL, and that the optimal prognostic staging system remains a controversial issue.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adolescente , Adulto , Fatores Etários , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Transplante de Medula Óssea , Terapia Combinada , Esquema de Medicação , Feminino , Humanos , L-Lactato Desidrogenase/sangue , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/enzimologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/cirurgia , Prognóstico , Análise de Regressão
3.
J Clin Oncol ; 12(12): 2543-51, 1994 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-7527453

RESUMO

PURPOSE: Intensive chemotherapy followed by autotransplantation has given promising results in partially responding or sensitive relapsed patients with aggressive non-Hodgkin's lymphoma. In 1987, we designed a randomized study to evaluate the potential benefit of a high-dose regimen containing cyclophosphamide, carmustine, and etoposide (CBV) followed by autotransplantation over a consolidative sequential chemotherapy (ifosfamide, etoposide, asparaginase, and cytarabine) in patients in first complete remission with intermediate- and high-grade non-Hodgkin's lymphoma. PATIENTS AND METHODS: Patients were younger than 55 years and had at least one adverse prognostic factor. Induction treatment was that of the LNH84 protocol with an open randomization on the anthracycline. Patients in complete remission were further randomly assigned to receive either consolidation procedure. RESULTS: After induction treatment, 464 patients were assessable for the consolidation phase. With a median follow-up duration of 28 months, the 3-year disease-free survival rate was 52% (95% confidence interval, 45% to 59%) in the sequential chemotherapy arm and 59% (95% confidence interval, 52% to 66%) in the autologous transplant arm (P = .46, relative risk = 0.90). The 3-year survival rate did not differ between sequential chemotherapy and autotransplantation, at 71% (95% confidence interval, 64% to 78%) and 69% (95% confidence interval, 62% to 76%), respectively (P = .60, relative risk = 1.11). CONCLUSION: For such a subset of patients, consolidation with the CBV regimen followed by autologous bone marrow transplantation is not superior to sequential chemotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Medula Óssea , Linfoma não Hodgkin/terapia , Adolescente , Adulto , Bleomicina/administração & dosagem , Carmustina/administração & dosagem , Intervalos de Confiança , Ciclofosfamida/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Etoposídeo/administração & dosagem , Seguimentos , Humanos , Pessoa de Meia-Idade , Prednisolona/administração & dosagem , Estudos Prospectivos , Indução de Remissão , Fatores de Risco , Transplante Autólogo , Vindesina/administração & dosagem
4.
Leukemia ; 7(3): 410-7, 1993 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-8383256

RESUMO

Rearrangements of the BCL2 gene and expression of bcl-2 protein were analyzed in a series of 64 cases of follicular lymphomas in order to establish a relationship between the rearrangements and the protein overexpression. Of the 64 cases, 41 showed BCL2 rearrangement involving one of the three breakpoint clusters: 30 in mbr, eight in mcr, and three in vcr. A double rearrangement mbr+vcr was detected in two cases. Twenty cases with bcl-2 protein expression in tumor cells exhibited no apparent rearrangement, suggesting the possible existence of other mechanisms activating the gene. Interestingly, expression of the LMP1 protein, the Epstein-Barr virus (EBV) encoded gene, whose capacity to induce BCL2 has been recently demonstrated, was only found in 2/41 cases in which BCL2 was rearranged. These data suggest that EBV infection is not an important mechanism in the activation of BCL2 in follicular lymphoma.


Assuntos
Regulação Neoplásica da Expressão Gênica/fisiologia , Linfoma Folicular/genética , Proteínas Proto-Oncogênicas/genética , Antígenos Virais/fisiologia , Rearranjo Gênico/fisiologia , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/imunologia , Herpesvirus Humano 4/fisiologia , Humanos , Imuno-Histoquímica , Linfoma Folicular/química , Linfoma Folicular/imunologia , Proteínas Proto-Oncogênicas/análise , Proteínas Proto-Oncogênicas c-bcl-2 , Ativação Transcricional , Translocação Genética/genética , Regulação para Cima/fisiologia , Proteínas da Matriz Viral/fisiologia
5.
Arch Intern Med ; 147(5): 898-901, 1987 May.
Artigo em Inglês | MEDLINE | ID: mdl-3579441

RESUMO

Five male patients with the persistent generalized lymphadenopathy syndrome also had a sicca complex. Salivary gland biopsy specimens showed diffuse lymphocytic infiltration of the glandular parenchyma. Serum autoantibodies and rheumatoid factor were not detected. All patients had IgG antibodies to human immunodeficiency virus and IgG to the viral capsid antigen of Epstein-Barr virus. These five patients had benign lymphocytic infiltrates in other organs (lung, liver, and kidneys). Sicca complex may be one of the various manifestations of the lymphoid hyperplasia noted in human immunodeficiency virus-infected patients. In these patients, the sicca complex showed specific features related to male predominance, lack of serum autoantibodies, and peripheral-blood T-lymphocyte subset distribution.


Assuntos
Complexo Relacionado com a AIDS/complicações , Xeroftalmia/etiologia , Xerostomia/etiologia , Complexo Relacionado com a AIDS/imunologia , Complexo Relacionado com a AIDS/patologia , Adulto , Anticorpos Antivirais/análise , Humanos , Imunoglobulina G/análise , Linfócitos/patologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Glândulas Salivares Menores/patologia
6.
Arch Intern Med ; 149(10): 2359-61, 1989 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-2802902

RESUMO

Two patients presented with a large tumoral nasopharyngeal lesion with obstructive symptoms, which suggested a malignant tumor. They were black men of Caribbean origin who were infected with human immunodeficiency virus 1. In both cases, histologic examination revealed intense but benign lymphoid follicular hyperplasia, and immunohistochemical studies were consistent with its polyclonal nature. DNA studies performed on tumoral tissue failed to disclose immunoglobulin or T-cell receptor gene rearrangements. In one biopsy specimen, DNA hybridization using Epstein-Barr virus-specific probes showed no evidence of Epstein-Barr virus-DNA sequences. The nasopharynx can be involved in the diffuse extranodal lymphoid hyperplasia associated with human immunodeficiency virus infection.


Assuntos
Síndrome da Imunodeficiência Adquirida/complicações , Hiperplasia do Linfonodo Gigante/etiologia , Neoplasias Nasofaríngeas/etiologia , Adulto , Humanos , Masculino
7.
Int J Radiat Oncol Biol Phys ; 26(3): 397-405, 1993 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-7685749

RESUMO

PURPOSE: To evaluate two regimens of chemotherapy followed by high dose total or subtotal nodal irradiation in advanced Stages of Hodgkin's disease. METHODS AND MATERIALS: From October 1980 to September 1985, 70 patients with Hodgkin's disease, with clinical Stages IIIB (35 cases) and IV (35 cases) were treated with combined modality therapy. Patients were randomly assigned to receive four cycles of chemotherapy, mechlorethamine, vincristine, procarbazine and prednisone (MOPP) versus the same regimen alternating with adriamycin, bleomycin, vinblastine and dacarbazine, ABVD-derived regimen, followed by high-dose (40 Gy) total or subtotal nodal irradiation. Because of partial response, 13 patients (18.5%) got additional chemotherapy (1-4 cycles). RESULTS: After chemotherapy, 49 patients (70%) achieved complete remission or good partial response and 15 patients (21.5%) partial response. Five primary failures (7%) and one death (1.5%) occurred. After combined modality therapy, 59 patients (84%) achieved complete remission, one patient partial response (1.5%) and eight patients (11.5%) failed to primary treatment. Two toxic deaths (3%) were observed during initial treatment. There was no significant difference in response rates between MOPP/radiotherapy and MOPP/ABVD/radiotherapy. Nine patients relapsed (15%). A total of 21 patients died, 13 because of Hodgkin's disease and eight from other causes. High dose total or subtotal nodal irradiation following four courses of chemotherapy was feasible, although hematological toxicity grade > or = 2 (World Health Organization) was observed in one-third of the patients, particularly in patients aged over 40. The median duration of follow-up was 75 months. Actuarial survival curves indicate a 8 years disease-free survival and survival of 70% and 65% respectively, without any significant difference between the two regimens. Because of hematological toxicity, the percentage of planned full treatment was lower in MOPP/radiotherapy regimen. CONCLUSION: These results lead to recommend the alternating regimen. Patients restaged as poor responders after initial chemotherapy did not survive for long. More intensive treatment is now proposed for this subgroup of patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/terapia , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bleomicina/administração & dosagem , Terapia Combinada , Dacarbazina/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/radioterapia , Humanos , Masculino , Mecloretamina/administração & dosagem , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Procarbazina/administração & dosagem , Estudos Prospectivos , Análise de Sobrevida , Taxa de Sobrevida , Vimblastina , Vincristina/administração & dosagem
8.
Am J Surg Pathol ; 20(7): 877-88, 1996 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-8669537

RESUMO

Among non-Hodgkin's lymphomas, primary mediastinal large B-cell lymphoma (PMLCL) has been considered a separate entity that has specific clinical and histological aspects and a poor prognosis. In this study, we reexamined the clinicopathologic features and the response to current treatment of 141 PMLCL and compare them with 916 nonmediastinal large B-cell lymphomas (NMLCL) recorded in the same period and treated with similar combined chemotherapy. The clinical features of PMLCL at diagnosis were largely homogeneous and distinct from NMLCL, with a predilection for young women (59% with a mean age of 37 years versus 42% with a mean age of 54 years), bulky tumor (77% versus 7%, p < 10(4)), high serum lactic dehydrogenase (LDH) level 76% versus 51%, p < 10(4)), and frequent intrathoracic extension to adjacent organs such as pleura, pericardium, and lung. By contrast, extrathoracic or hematologic dissemination was uncommon (2% of bone marrow involvement versus 17%). All patients had diffuse large B-cell nonimmunoblastic, nonanaplastic lymphomas. Histological analysis of the 141 PMLCL evaluated two common patterns: the presence of large cells with clear cytoplasm (found in 38% of cases) and the presence of fibrosis (marked in 25% of cases). The presence of clear cells or intense fibrosis did not constitute prognostic indicators. Immunologic and molecular analysis assessed the profile of bcl-2 expression and the presence of Epstein-Barr virus (EBV) in PMLCL: 30% expressed a high level of bcl-2 protein; EBER RNAs were detected by in situ hybridization in only two of the 41 cases tested. Monotypic light chain restriction could be demonstrated in seven of the 41 PMLCL tested on fixed-section. Treated with polychemotherapy regimens without radiotherapy, 79% of PMLCL patients achieved a complete remission compared with 68% in the NMLCL patient group (p = 0.01). Overall, 3-year survival rates were estimated at 66 and 61%, respectively (p = 0.05), and disease-free survival rates were not significantly different (61 versus 64%). Stratified analysis on the International Prognostic Index (based on age, tumor stage, serum LDH level, and performance status) showed no difference in the overall and disease-free survivals between the two lymphoma groups. In conclusion, PMLCL can be combined with other diffuse large B-cell lymphomas on morphologic grounds; it is not associated with EBV. It responds favorably to treatment and should be managed like other high-grade lymphomas of equivalent histology. However, the uncommon clinical presentation makes it a distinct entity.


Assuntos
Linfoma de Células B/patologia , Linfoma Difuso de Grandes Células B/patologia , Neoplasias do Mediastino/patologia , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estudos de Coortes , Feminino , França , Herpesvirus Humano 4/isolamento & purificação , Humanos , Imuno-Histoquímica , L-Lactato Desidrogenase/sangue , Linfoma de Células B/tratamento farmacológico , Linfoma de Células B/virologia , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/virologia , Masculino , Neoplasias do Mediastino/tratamento farmacológico , Neoplasias do Mediastino/virologia , Pessoa de Meia-Idade , Prognóstico
9.
Hum Pathol ; 23(3): 317-23, 1992 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-1555841

RESUMO

Sarcoidosis is a chronic granulomatous disease that may be considered to be a human model for the delayed-type hypersensitivity reaction. The expression of cytokine genes in organs displaying sarcoid granulomas was analyzed by in situ hybridization with several cytokine probes using biopsies from 11 sarcoid lymph nodes. We detected cells expressing interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), IL-6, IL-2, and interferon-gamma (IFN-gamma) genes in all lymph nodes. The major finding of this study was that cytokine genes are independently expressed. Of the monokine genes, the IL-1 beta gene was preferentially expressed. The distribution of cells containing IL-1 beta mRNA was characterized by their amalgamation in clusters inside sarcoid granulomas. Cells expressing the TNF-alpha gene were located exclusively inside granulomas and were always scattered. Cells expressing the IL-6 gene or the IL-1 alpha gene were found scattered inside sarcoid granulomas and in the residual lymphoid tissue. The number of cells expressing the IL-1 beta gene was significantly higher than that of cells expressing TNF-alpha gene (P = .001), IL-6 gene (P = .007), or IL-1 alpha gene (P less than .001). Of the cells expressing lymphokine genes, those expressing the IFN-gamma gene were 31.9 (+/- 7.6) times more frequent than those expressing the IL-2 gene (P less than .001). Cells containing IFN-gamma mRNA were detected mainly inside sarcoid granulomas, whereas cells containing IL-2 mRNA were randomly distributed. These results show that each monokine gene or lymphokine gene can be independently expressed in vivo. The high expression level of the IL-1 beta gene and the IFN-gamma gene inside granulomas may be specific to delayed-type hypersensitivity immune reactions.


Assuntos
Citocinas/biossíntese , Expressão Gênica , Doenças Linfáticas/metabolismo , Sarcoidose/metabolismo , Citocinas/genética , Humanos , Interferon gama/biossíntese , Interferon gama/genética , Interleucina-1/biossíntese , Interleucina-1/genética , Doenças Linfáticas/genética , Hibridização de Ácido Nucleico , RNA Mensageiro/análise , Sarcoidose/genética
10.
Am J Clin Pathol ; 95(1): 55-62, 1991 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-1899000

RESUMO

In situ hybridization with specific RNA radiolabeled probes was used to analyze the production of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) by 21 low-grade follicular lymphomas (FLs). All of the 21 FLs tested contained lymphokine-synthesizing cells in the interfollicular and follicular areas. Enumeration of lymphokine synthesizing cells indicated heterogeneous IL-2 production among lymph nodes tested; 2 of the 21 had much higher densities of IL-2-producing cells (855 and 570/cm2) than did the remaining 19 (mean, 92 +/- 15/cm2). IFN-gamma-producing cells displayed no such variation (mean, 77 +/- 8 IFN-gamma-producing cells/cm2). The mean IL-2/IFN-gamma-producing cell ratio was 2.69 +/- 0.84, indicating preferential induction of IL-2. The detailed distribution of lymphokine-producing cells showed that IL-2 and IFN-gamma-producing cells were located mainly in the follicular areas. The mean follicular/interfollicular ratio was 1.82 +/- 0.16 for IL-2 and 1.92 +/- 0.19 for IFN-gamma-producing cells. The results show that T-cell activation, defined by lymphokine production, occurs in FL lymph nodes in direct contact with malignant B cells. Thus, lymphokine production may play an important role in the control of tumor growth, which is the result of interaction between tumor cells and host-derived immune reaction.


Assuntos
Interferon gama/metabolismo , Interleucina-2/metabolismo , Linfoma Folicular/metabolismo , Humanos , Linfonodos/metabolismo , Linfonodos/patologia , Linfoma Folicular/patologia , Receptores de Interleucina-2/metabolismo
11.
Cancer Genet Cytogenet ; 73(1): 65-8, 1994 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-8174077

RESUMO

Cytogenetic studies in six patients with Richter's syndrome (RS) showed complex chromosome abnormalities and chromosomal instability in five. No specific chromosomal abnormality was detected. Chromosomes 14 and 11 were the most frequently involved. Neither deletion of 13q14 nor complete trisomy 12 was observed. Two patients had structural rearrangement of 12q with t(5;12)(q21-q22;q23-q24). The involvement of this region of chromosome 12 may be significant, although not specific for chronic lymphocytic leukemia. These results were compared to those found in cytogenetically studied RS patients from the literature.


Assuntos
Aberrações Cromossômicas , Linfoma Difuso de Grandes Células B/genética , Idoso , Feminino , Humanos , Imunofenotipagem , Linfoma Difuso de Grandes Células B/imunologia , Linfoma Difuso de Grandes Células B/fisiopatologia , Masculino , Pessoa de Meia-Idade , Síndrome
12.
Leuk Lymphoma ; 22(5-6): 449-56, 1996 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-8882958

RESUMO

Autologous stem-cell transplantation is widely used as part of the treatment of poor prognosis lymphoma patients. Since 1986, peripheral blood progenitor cells (PBPC) mobilized by chemotherapy and/or hematopoietic growth factors have progressively been used instead of autologous bone marrow (BM) cells. Toxicity, engraftment and long-term outcome were compared in a population of relapsing or refractory lymphoma patients given high-dose therapy. During 1986 to 1993, 150 patients with refractory or relapsed non-Hodgkin's lymphomas (n = 93) or Hodgkin's disease (n = 57) received intensive therapy followed by the reinjection of BM (n = 72) or PBPC (n = 78). PBPC were collected by aphereses during the phase of hematologic recovery after mobilization by chemotherapy alone (n = 36) or associated with GCSF (n = 43). Conditioning regimens included chemotherapy alone in 77%, associated with total body irradiation (TBI) in 23%. After stem-cell reinfusion, 55% of the PBPC group received GCSF versus 24% in the BM group. Results show that the median time to neutrophil counts > 500/microliters and platelets > 50,000/microliters was significantly shorter in the PBPC than the BM group, respectively 13 versus 23 days and 18 versus 26 days (P < 0.05). This difference remained significant (P < 0.05) when patients were stratified according to the administration or not of GCSF after transplantation. PBPC grafting after high-dose therapy was associated with a median reduction of the hospital stay of 10 days. The majority of patients (90%) maintained normal blood counts at 3 months, and no secondary graft failure was observed in either group. The use of TBI in the conditioning regimen was the only significant factor affecting long-term hematologic recovery. For relapsing patients with histologically aggressive lymphomas, overall survival and failure-free survival were similar in both groups. In conclusion, PBPC transplantation is a safe procedure associated with improvement of hematopoietic recovery and a shortened hospital stay.


Assuntos
Transplante de Medula Óssea , Transplante de Células-Tronco Hematopoéticas , Linfoma/sangue , Linfoma/terapia , Adolescente , Adulto , Intervalo Livre de Doença , Feminino , Humanos , Contagem de Leucócitos , Linfoma/mortalidade , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Recidiva , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de Tempo , Transplante Autólogo , Irradiação Corporal Total
13.
Leuk Lymphoma ; 35(5-6): 555-65, 1999 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-10609793

RESUMO

Between March 1992 and August 1993, thirty patients with hairy cell leukemia (HCL) were treated in a single institution with 2-chlorodeoxyadenosine (2-CdA) for one course (N=27) or two courses at six month interval (N=3). Sixteen patients were previously untreated, 14 had been treated with alpha interferon (alpha IFN) (N=5), alpha IFN and splenectomy (N=8) and splenectomy, alpha IFN and Deoxycoformycin (N=1). Overall results in 29 evaluable patients were: 25 CR (86%), 3 PR (10%), one failure. The three PR patients relapsed after 18, 24 months and five years. Two were retreated successfully. Two CR patients relapsed after five years. Careful clinical survey, sequential bone marrow biopsies (BMB) with DBA44 immunostaining for assessment of response and detection of residual disease and serially evaluation of lymphocyte subsets counts were performed. Results of bone marrow biopsies study show 1) a progressive reduction in hairy cell infiltration during the first six months after therapy and not after that indicating that the best moment for the evaluation of response may be the sixth month, 2) the persistence of a very small number of DBA44+ cells (80% of BMB). There was a correlation between the presence of > 5% DBA44 positive cells on 6th month BMB and relapse. 60% had an absolute CD4+ lymphocyte count less than 0.2 10(9)/l at least on one examination after treatment. CD4+ lymphocyte level persisted less than baseline level in 8/18 patients tested after four and/or five years. Lymphopenia was less marked in splenectomized patients: 7/7 splenectomized patients tested have recovered a CD4+ lymphocyte count equal to pretherapy level compared to 3/11 non splenectomized patients (p: 0.004). Three opportunistic infections were observed early (first 6 months) after 2CdA therapy: pneumocystis pneumonia, retinitis due to toxoplasma in the patient who failed and legionella pneumonia in a patient retreated after relapse. Two patients developed a second carcinoma 6 and 12 months after therapy. Five patients died, three from a cause unrelated to HCL, one from HCL and one from infection while in second CR. At five years, overall survival is 83% and progression free survival is 66%. Our study shows 1) long-lasting response in the majority of patients after 2-CdA, 2) a correlation between persistent minimal residual disease detected with DBA44 immunostaining and occurrence of relapse and 3) a profound and persistent CD4+ lymphopenia more marked in non splenectomized patients.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Cladribina/uso terapêutico , Leucemia de Células Pilosas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Medula Óssea/patologia , Contagem de Linfócito CD4 , Terapia Combinada , Progressão da Doença , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Infecções/epidemiologia , Infecções/etiologia , Interferon-alfa/uso terapêutico , Leucemia de Células Pilosas/mortalidade , Leucemia de Células Pilosas/patologia , Leucemia de Células Pilosas/cirurgia , Leucemia de Células Pilosas/terapia , Masculino , Pessoa de Meia-Idade , Neoplasia Residual , Segunda Neoplasia Primária/epidemiologia , Infecções Oportunistas/epidemiologia , Infecções Oportunistas/etiologia , Pentostatina/uso terapêutico , Indução de Remissão , Esplenectomia , Taxa de Sobrevida
14.
Thromb Res ; 63(5): 509-19, 1991 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-1755004

RESUMO

Veno occlusive disease (VOD) is a frequent complication of allogenic bone marrow transplantation (BMT) for which no predictive blood markers are available. 39 patients grafted for severe aplastic anemia (18), and leukemia (21) were prospectively studied. Of the 39 patients, 5 leukemic patients, but no aplastic patients developed VOD. In all the 5 patients with VOD complications we demonstrated a decrease in factor VII and in protein C before the clinical onset of the disease and before any changes in hepatic enzymes were observed. This decrease is the earliest sign of hepatic involvement by the VOD suggesting that the determination of Factor VII and protein C can be used as a prediction test to identify the patients who are at risk of developing VOD after transplantation. In addition, a toxicity of the endothelial cells was suggested by the observed increase in von Willebrand factor and in Serum Angiotensin Converting Enzyme. Signs of endothelial toxicity was more pronounced in leukemic than in aplastic patients.


Assuntos
Fatores de Coagulação Sanguínea/análise , Transplante de Medula Óssea/efeitos adversos , Endotélio Vascular/química , Hepatopatia Veno-Oclusiva/etiologia , Biomarcadores/sangue , Testes de Coagulação Sanguínea , Hepatopatia Veno-Oclusiva/sangue , Hepatopatia Veno-Oclusiva/diagnóstico , Humanos , Fígado/metabolismo , Estudos Prospectivos , Fatores de Risco
15.
Bull Cancer ; 80(2): 102-10, 1993 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-7513565

RESUMO

We describe the production of 13 new monoclonal antibodies induced by the product of the human p53 tumor suppressor gene. All these monoclonal antibodies recognize human p53 irrespective of the detection technique: ELISA, immunoblot or immunoprecipitation. These antibodies can be divided into four groups according to such criteria as localization of the recognized epitopes and reactivity with p53 originating from other organisms. One monoclonal antibody was successfully used for immunohistochemistry detection of p53 accumulation in breast carcinoma. This novel panel of monoclonal antibodies represents a further tool for the study of the p53 protein.


Assuntos
Anticorpos Monoclonais/biossíntese , Neoplasias da Mama/genética , Genes p53 , Animais , Neoplasias da Mama/imunologia , Ensaio de Imunoadsorção Enzimática , Epitopos/análise , Feminino , Expressão Gênica , Humanos , Immunoblotting , Imuno-Histoquímica , Neoplasias Mamárias Animais/genética , Neoplasias Mamárias Animais/imunologia , Camundongos , Camundongos Endogâmicos BALB C
16.
Rev Med Interne ; 14(10): 959, 1993.
Artigo em Francês | MEDLINE | ID: mdl-8009055

RESUMO

Hodgkin's disease seems to be more frequent in HIV infected patients than in general population with peculiar clinical and pathological aspects. We describe 40 cases of Hodgkin's disease in HIV infected patients followed between 1983 and 1993.


Assuntos
Doença de Hodgkin , Linfoma Relacionado a AIDS , Adulto , Feminino , Doença de Hodgkin/mortalidade , Doença de Hodgkin/fisiopatologia , Humanos , Linfoma Relacionado a AIDS/mortalidade , Linfoma Relacionado a AIDS/fisiopatologia , Masculino , Pessoa de Meia-Idade
17.
Ann Pathol ; 11(5-6): 326-33, 1991.
Artigo em Francês | MEDLINE | ID: mdl-1804152

RESUMO

Histiocytic necrotizing lymphadenitis of Kikuchi is a rare benign disease. Characteristically, patients are young women with cervical adenopathy which may be associated with fever. Histologically, the involved lymph nodes show focal, well-circumscribed, paracortical, necrotizing lesions which contain karyorrhectic debris and aggregates of large mononuclear cells but no neutrophils. This disorder can be misdiagnosed as malignant lymphoma. The histological features seem to be related to delayed-type hypersensitivity but the antigenic stimulus is still unknown. The clinicopathological and immunohistochemical features of histiocytic necrotizing lymphadenitis in 11 patients are described. In necrotic areas, the majority of cells represent histiocytes and T cells (predominantly of CD8 phenotype). The involved lymph nodes were localized to several cervical sites (commonly jugular area).


Assuntos
Linfadenite/patologia , Adolescente , Adulto , Feminino , Humanos , Imuno-Histoquímica , Masculino , Necrose
18.
Ann Pathol ; 6(1): 13-22, 1986.
Artigo em Francês | MEDLINE | ID: mdl-3521624

RESUMO

Granulomatous lesions of the cranio-facial area are frequent and various in their nature: lymphohistiocytic with or without eosinophils, tuberculoid-like with epithelioid and giant cells, or sometimes made essentially of giant cells. Their etiology can be known or easy to find: foreign body granuloma, sarcoidosis, leprosy, rhinoscleroma, fungal diseases especially zygomycosis and rhinosporidiosis, parasitic diseases. The lethal midline granuloma is a clinical entity characterized by its necrotic and relentlessly progressive destructive presentation. After elimination of a malignant process, especially lymphoid, and of a Wegener's granulomatosis the diagnosis will be "idiopathic midline non-healing granuloma". Some of them will stay located at the facial area; others will disseminate as a malignant disease. Central giant cell granuloma and histiocytosis X, especially eosinophilic granuloma, are two other varieties of granuloma, different of the former granulomatous infiltrates by their clinical presentation and their evolution.


Assuntos
Face , Granuloma/patologia , Crânio , Criança , Diagnóstico Diferencial , Granuloma Eosinófilo/patologia , Face/patologia , Corpos Estranhos/complicações , Granuloma/diagnóstico , Granuloma/etiologia , Granuloma de Células Gigantes/patologia , Granuloma Letal da Linha Média/patologia , Granulomatose com Poliangiite/patologia , Histiocitose de Células de Langerhans/patologia , Humanos , Infecções/complicações , Doenças Maxilares/patologia , Doenças Parasitárias/complicações , Rinoscleroma/patologia , Rinosporidiose/complicações , Rinosporidiose/patologia , Sarcoidose/patologia , Crânio/patologia
19.
Ann Pathol ; 6(2): 137-43, 1986.
Artigo em Francês | MEDLINE | ID: mdl-3015160

RESUMO

The incidence of malignant lymphoma after bone marrow transplant seems very low. A 31 years old patient was treated with allogeneic bone marrow transplantation for chronic myeloid leukemia; she develops 12 days after grafting a severe graft-versus-host disease (GVH) refractory to treatment with steroids and Cyclosporin A. The GVH was then treated with an anti-T lymphocyte monoclonal antibody (OKT3). The disease responded dramatically to this treatment but the GVH reappeared immediately at the end of OKT3 therapy and the patient died the 103th day after grafting. The autopsy revealed extensive lymphoid infiltrate by a monoclonal IgM K immunoblastic proliferation. After organ or bone marrow transplant, a wide spectrum of lymphoid lesions can be observed, ranging from follicular or diffuse polyclonal hyperplasia to monoclonal immunoblastic lymphoma. The criteria for monoclonality are discussed. Epstein-Barr Virus infection associated with immunosuppressive treatments play probably a major role in the occurrence of a malignant lymphoma.


Assuntos
Anticorpos Monoclonais/efeitos adversos , Transplante de Medula Óssea , Doença Enxerto-Hospedeiro/terapia , Linfoma/etiologia , Adulto , Anticorpos Monoclonais/uso terapêutico , Feminino , Herpesvirus Humano 4 , Humanos , Terapia de Imunossupressão/efeitos adversos , Leucemia Mieloide/terapia , Linfoma/patologia , Infecções Tumorais por Vírus
20.
Ann Pathol ; 5(2): 125-9, 1985.
Artigo em Francês | MEDLINE | ID: mdl-3899127

RESUMO

A case of papillary adenocarcinoma, developed on the urinary bladder neck is reported. This tumor is histologically identical to so called endometrial carcinoma of the prostate. Immunohistochemistry showed acid phosphatases and prostatic specific antigen (PSA) positive cells. Electron microscopy disclosed secretory vacuoles consistent with a prostatic origin. The histogenesis of endometrial carcinoma is briefly discussed likewise the precise site of origin of the reported case.


Assuntos
Adenocarcinoma Papilar/patologia , Neoplasias da Bexiga Urinária/patologia , Fosfatase Ácida/análise , Adenocarcinoma Papilar/análise , Idoso , Antígenos de Neoplasias/análise , Citoplasma/patologia , Histocitoquímica , Humanos , Técnicas Imunológicas , Masculino , Microscopia Eletrônica , Próstata/imunologia , Neoplasias da Próstata/patologia , Neoplasias da Bexiga Urinária/análise , Vacúolos/patologia
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