RESUMEN
Minichromosome maintenance protein 6 (MCM6) is one of six proteins of the MCM family which are involved in the initiation of DNA replication and thus represent a marker of proliferating cells. Since the level of cell proliferation is the most valuable predictor of survival in mantle cell lymphoma (MCL), we investigated lymph node biopsy specimens from 70 patients immunohistochemically with a monoclonal antibody against MCM6. The percentage of MCM6 expressing lymphoma cells ranged from 12.0 to 95.6%, with a mean of 61.0%, and was significantly higher than the percentage of Ki-67-positive cells (P<0.0001). Surprisingly, the ratio of MCM6-positive cells to Ki-67-positive cells was higher than in normal stimulated peripheral blood mononuclear cells, indicating a cell early G1-phase arrest in MCL. A high MCM6 expression level of more than 75% positive cells was associated with a significantly shorter overall survival time (16 months) compared to MCL with a low MCM6 expression level of less than 25% (no median reached, P<0.0001). Multivariate analysis revealed MCM6 to be an independent predictor of survival that is superior to the international prognostic factor and the Ki-67 index. Therefore, aside from gene expression profiling, immunohistochemical detection of MCM6 seems to be the most promising marker for predicting the outcome in MCL.
Asunto(s)
Proteínas de Ciclo Celular/biosíntesis , Linfoma de Células del Manto/genética , Linfoma de Células del Manto/patología , Biopsia , Proteínas de Ciclo Celular/genética , Proliferación Celular , Femenino , Perfilación de la Expresión Génica , Humanos , Inmunohistoquímica , Antígeno Ki-67/análisis , Ganglios Linfáticos/patología , Masculino , Persona de Mediana Edad , Componente 6 del Complejo de Mantenimiento de Minicromosoma , Análisis Multivariante , Valor Predictivo de las Pruebas , Pronóstico , Análisis de SupervivenciaRESUMEN
Mantle cell lymphoma (MCL) is a malignant lymphoma associated with a relatively aggressive clinical course and a median overall survival time of 3-4 years. Treatment usually consists of combination chemotherapy, often including topoisomerase (topo) inhibitors such as doxorubicin, etoposide and mitoxantrone. Topo IIalpha is an enzyme that is needed whenever uncoiling of DNA is necessary during the cell cycle. The enzyme is a marker of cell proliferation. We analyzed the expression of topo IIalpha in relation to Ki-67 and the clinical outcome in patients with MCL. Biopsy specimens from 95 untreated patients enrolled in two multicenter trials (1975-1985) were investigated immunohistochemically with monoclonal antibodies against topo IIalpha (Ki-S4) and Ki-67 (Ki-S5). Patients with low (0-10%) topo IIalpha expression had a median overall survival time of 49.0 months, compared to 17.0 months for patients with high (more than 10%) topo IIalpha expression. The Kaplan-Meier analysis showed a significant difference in the overall survival time related to the percentage of topo IIalpha (P<0.001) and Ki-67 (P<0.001) positive tumor cells. Multivariate Cox regression analysis revealed the expression of topo IIalpha as the most important prognostic factor (P<0.001) in MCL superior to the international prognostic index (IPI), the Ki-67 index and other clinical characteristics.
Asunto(s)
ADN-Topoisomerasas de Tipo II/análisis , Linfoma de Células del Manto/enzimología , Antígenos de Neoplasias , Antineoplásicos/uso terapéutico , Biomarcadores/análisis , División Celular , Proteínas de Unión al ADN , Femenino , Humanos , Inmunohistoquímica , Antígeno Ki-67/análisis , Linfoma de Células del Manto/tratamiento farmacológico , Linfoma de Células del Manto/mortalidad , Masculino , Persona de Mediana Edad , Pronóstico , Análisis de Regresión , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
The transcription factor AML1 (CBFA2) is indispensable for early fetal hematopoiesis, but also transactivates target genes which are important for further downstream hematopoiesis. However, little is known about the impact of AML1 on lineage-committed stages. We investigated the transcription of AML1 in subfractions of four normal adult bone marrow aspirates isolated by fluorescence-activated cell sorting. AML1 is transcribed in early (CD34+/CD38-) and late (CD34+/CD38+) hematopoietic progenitors, B-cell precursors (CD10+/CD19+) as well as in immature monocytes (CD14-/CD11c+), myeloid (CD15+/CD33+ and CD15+/CD33-) and erythroid (GPA+/CD3-/CD45-) cells, but not in T lymphocytes (GPA-/CD3+/CD45+). These data suggest that in adult hematopoiesis AML1 may be critically involved in differentiation of early hematopoietic progenitors, erythroid cells, and lymphoid precursors. These subfractions are interesting targets to study the importance of AML1 in definitive hematopoiesis.
Asunto(s)
Células de la Médula Ósea/fisiología , Proteínas de Unión al ADN/genética , Proteínas Proto-Oncogénicas , Factores de Transcripción/genética , Transcripción Genética , Adulto , Antígenos CD/análisis , Células de la Médula Ósea/inmunología , Separación Celular , Subunidad alfa 2 del Factor de Unión al Sitio Principal , Células Precursoras Eritroides/fisiología , Citometría de Flujo , Células Madre Hematopoyéticas/fisiología , Humanos , Monocitos/fisiología , Células Mieloides/fisiología , Valores de Referencia , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
In peripheral blood of at least 50% of healthy individuals, the translocations t(9;22) BCR/ABL, t(14;18) IgH/BCL-2, t(2;5) NPM-ALK and MLL duplications, which characterize chronic myelogenous leukemia and acute lymphoblastic leukemia, follicular lymphoma, anaplastic large cell lymphoma, and acute myelogenous leukemia, respectively, are detectable by sensitive polymerase chain reaction (PCR). No structural differences between these aberrations in normal or disturbed hematopoiesis are apparent. While the total count of t(9;22)- and t(14;18)-positive cells does not exceed 10(4), those with MLL duplications are more frequent and account for approximately 10(7) cells in the total blood pool. t(14;18)-positive cells seem to be immortalized, but the biological consequences of the other aberrations in positive healthy persons have not been studied in detail. Due to the high frequency of positive individuals, most of them will not suffer from the correspondent leukemia or lymphoma, and criteria for subgroups that may be at a higher risk remain to be determined. Most likely, the number of genetic aberrations in healthy individuals, which so far are only associated with hematopoietic disorders, will increase in the near future.
Asunto(s)
Aberraciones Cromosómicas , Genoma Humano , Frecuencia de los Genes , Humanos , Leucemia/genética , Linfoma/genética , Valores de ReferenciaRESUMEN
CAMPATH-1H (CP-1H) is a humanized monoclonal antibody directed against the CD52 antigen with promising therapeutic effects in patients with small cell lymphocytic non-Hodgkin's lymphomas (NHL) of B- and T-cell type. We report about the response and toxicity of CP-1H in 18 patients with B-cell NHL who were treated in four clinical centers in Germany. Sixteen patients suffered from a low-grade and two from a high-grade NHL. All patients had received chemotherapy before and had either relapsed or were refractory to conventional therapy. Two patients received CP-1H in a dose-range finding trial once weekly and 16 patients as a fixed dose of 30 mg three times weekly. Of 18 patients, 8 (44%) achieved a clinical response, 2 (11%) had stable disease, and 5 (28%) had progressive disease. Four patients could not be evaluated for response because of death (two patients) and serious adverse events (two patients). All patients with response to CP-1H had a low-grade NHL. Nonhematological toxicity was severe in two patients who suffered from WHO grade III/IV bronchospasm. Common acute adverse events (WHO grade I-III) included fever, chills, rigor, urticaria, nausea, and vomiting. Eleven patients suffered from bacterial or viral infections; some had recurrent infections. A total of 12 different infections were reported. The most frequent infections were caused by herpesvirus (seven patients). Hematological toxicity included thrombocytopenia in four and lymphocytopenia in seven patients. Although the antibody is humanized, the nonhematological toxicity was substantial and probably due to a cytokine release syndrome. Prophylactic treatment of the side effects is strongly recommended for patients treated either with CP-1H alone or in combination with chemotherapy.
Asunto(s)
Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Antineoplásicos/administración & dosificación , Antineoplásicos/administración & dosificación , Linfoma no Hodgkin/tratamiento farmacológico , Anciano , Alemtuzumab , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales Humanizados , Anticuerpos Antineoplásicos/efectos adversos , Antineoplásicos/efectos adversos , Femenino , Humanos , Infusiones Intravenosas , Linfoma no Hodgkin/patología , Masculino , Persona de Mediana Edad , Recurrencia , Resultado del TratamientoAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Anticuerpos Monoclonales/uso terapéutico , Ensayos Clínicos como Asunto , Relación Dosis-Respuesta a Droga , Humanos , Leucemia Linfocítica Crónica de Células B/clasificación , Leucemia Linfocítica Crónica de Células B/diagnóstico , Trasplante de Células Madre , Resultado del TratamientoRESUMEN
The efficacy and toxicity of a combination of fludarabine and cyclophosphamide (FC) was evaluated in patients with B-cell chronic lymphocytic leukaemia (CLL). Between April 1997 and July 1998, 36 patients with CLL (median age 59 years) received a regimen that consisted of fludarabine 30 mg/m(2) in a 30-min IV infusion, d 1-3, and cyclophosphamide 250 mg/m(2) in a 30-min IV infusion on d 1-3. Cycles were repeated every 28 d. Twenty-one patients had received between one and three different treatment regimens prior to the study, while 15 patients had received no prior therapy. The median Eastern Cooperative Oncology Group performance score was 1. One patient was at Binet stage A, 18 were stage B and 17 patients were stage C. Objective responses, assessed according to the revised guidelines of the National Cancer Institute-sponsored Working Group, were recorded in 29 out of 32 assessable patients (90.6%). Twenty-four partial remissions and five complete remissions were observed. Two patients showed no change and one patient showed disease progression. At February 2000, three of the responders had relapsed. Severe neutropenia, anaemia and thrombocytopenia (Common Toxicity Criteria grade 3 and 4) were observed in 25, six and six patients (69.4%, 16.7% and 16.7%) respectively. Other side-effects were uncommon. No treatment-related deaths and no grade 3 or 4 infections occurred. We conclude that the combination of fludarabine and cyclophosphamide showed significant activity in patients with CLL. Myelosuppression was the major side-effect. These results warrant further study on the FC combination in randomized trials.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Femenino , Humanos , Leucopenia/inducido químicamente , Masculino , Persona de Mediana Edad , Neutropenia/inducido químicamente , Trombocitopenia/inducido químicamente , Resultado del Tratamiento , Vidarabina/administración & dosificación , Vidarabina/efectos adversos , Vidarabina/análogos & derivadosRESUMEN
We treated 153 patients with de novo acute myeloid leukemia (AML) with two induction courses of conventional-dose cytosine arabinoside (ara-C) and idarubicin (AIDA) followed by either a third course of AIDA, high-dose ara-C or bone-marrow transplantation. The complete remission (CR) rate for all patients was 63.4%, with a higher CR rate for patients with a normal (versus unfavorable) karyotype (73.2% vs 52.5%; P=0.038). The probability of overall survival (OS) was 30.7% after 5 years (26.3% after 7 years). Improved OS at 5 years could be observed for patients up to 50 years old versus patients older than 50 years of age (37.6% vs 19.9%; P=0.001) and patients with a normal (versus unfavorable) karyotype (42.9% vs 14.1%; P=0.0016). Disease-free survival (DFS) after 5 years was 33.2% for all 97 CR patients and was significantly better for patients with a normal (versus unfavorable) karyotype (44.3% vs 12.3%; P= 0.003). Multivariate analysis revealed that the age for OS (P < 0.02) and the karyotype for both OS (P<0.03) and DFS (P< 0.05) were independent prognostic factors. In conclusion, AIDA is an effective and well-tolerated induction regimen (even in elderly patients) with a 5-year survival of more than 30% when combined with ara-C-containing postremission therapy. The karyotype is the most powerful prognostic factor for predicting the outcome of patients treated with this protocol.
Asunto(s)
Citarabina/uso terapéutico , Idarrubicina/uso terapéutico , Leucemia Mieloide/tratamiento farmacológico , Leucemia Mieloide/mortalidad , Enfermedad Aguda , Adolescente , Adulto , Anciano , Citarabina/toxicidad , Supervivencia sin Enfermedad , Femenino , Humanos , Idarrubicina/toxicidad , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/mortalidad , Masculino , Persona de Mediana Edad , Análisis Multivariante , Inducción de Remisión , Tasa de SupervivenciaRESUMEN
Platelet production is primarily regulated by the thrombopoietic cytokine thrombopoietin (TPO). In most cases thrombopoietin serum levels are determined by the rate of c-mpl receptor-mediated degradation after TPO uptake into platelets and megakaryocytes. The contribution of increased TPO protein synthesis by a translational mechanism was recently appreciated as the cause for hereditary thrombocythemia and will have to be elucidated in other conditions of thrombocytosis in association with increased TPO levels.
Asunto(s)
Proteínas de Neoplasias , Trombopoyetina/sangre , Síndrome de Inmunodeficiencia Adquirida/sangre , Adulto , Animales , Antineoplásicos/efectos adversos , Preescolar , Citocinas/sangre , Citocinas/farmacología , Infecciones por VIH/sangre , Enfermedades Hematológicas/sangre , Enfermedades Hematológicas/inducido químicamente , Enfermedades Hematológicas/genética , Humanos , Lactante , Recién Nacido , Proteínas Proto-Oncogénicas/metabolismo , Receptores de Citocinas/metabolismo , Receptores de Trombopoyetina , Trombocitopenia/sangre , Trombocitosis/etiología , Trombocitosis/metabolismo , Trombocitosis/virología , Trombopoyetina/efectos de los fármacosRESUMEN
Idarubicin is the first anthracycline that can be administered orally facilitating antineoplastic chemotherapy at an improved quality of life. In different studies idarubicin has proved clinical effectiveness in patients with advanced low grade non Hodgkin's lymphoma. We performed a phase II study in 19 patients with untreated and pretreated B-CLL of Binet stage A-C. Idarubucin was administered orally at a dose of 15 mg/m2 over 3 days every 4 weeks. Of 19 evaluable patients (m:f, 16:3, median age 64 years, range 41-80 years) 7 were previously untreated while 12 patients had received prior therapy with fludarabine, chlorambucil or similar non-anthracycline containing regimens. 12 pts had Binet stage C, 5 Binet stage B and 2 Binet stage A. Five patients achieved a partial remission (26%), 5 patients had stable disease (26%) and 9 patients showed progressive disease (47%), resulting in an overall response of 26% (5/19). There was no correlation of response rate with Binet stages or previous treatment regimens. Treatment associated side effects consisted predominantly of mild nausea and vomiting (26%) as well as minor infections (21%) and diarrhoea (16%). These data demonstrate that oral idarubicin as a single agent is well tolerated but of limited effectiveness in B-CLL. Further studies are needed to assess different doses and schedules of oral idarubucin and to test it in combination with other chemotherapeutic agents.
Asunto(s)
Antibióticos Antineoplásicos/uso terapéutico , Idarrubicina/uso terapéutico , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Administración Oral , Adulto , Anciano , Antibióticos Antineoplásicos/administración & dosificación , Femenino , Humanos , Idarrubicina/administración & dosificación , Masculino , Persona de Mediana EdadRESUMEN
This investigation studied the effects of cell preparation methods, different antibody panels and blood storage on antigen expression of abnormal B lymphocytes from patients with B-CLL. Blood specimens collected in Heparin de novo were processed by using conventional Hypaque-Ficoll density gradient centrifugation and whole blood lysis. These were stored for 3 days at 4 degrees C, 24 degrees C and 30 degrees C. Although clonal excess was detected by all antibody panels, significant differences could be observed in terms of molecules of equivalent fluorochromes (MEF/MESF units). Evaluation of 'weak and strong' staining is dependent on the antibody panel used. Immunofluorescent values for CD19 and CD45 were unchanged at 4 degrees C and 24 degrees C but immunoglobulin staining showed best results when blood was stored at 4 degrees C. Storage at 30 degrees C produced unreliable results. Abnormal B lymphocytes should be analysed immediately after the specimen is obtained. If shipment is necessary they should be kept at 4 degrees C. Surface immunoglobulins are the 'antigens' most sensitive to storage alterations. Sample alterations alone are sufficient to the correct classification of NHL, especially in the case of low-grade NHL.
Asunto(s)
Linfocitos B/patología , Inmunofenotipificación/métodos , Leucemia Linfocítica Crónica de Células B/patología , Anciano , Anticuerpos Monoclonales/inmunología , Linfocitos B/inmunología , Conservación de la Sangre , Diferenciación Celular , Femenino , Citometría de Flujo/métodos , Humanos , Leucemia Linfocítica Crónica de Células B/inmunología , Masculino , Persona de Mediana Edad , Coloración y Etiquetado/métodosRESUMEN
BACKGROUND AND OBJECTIVES: From a technical point of view two problems arise during the collection of peripheral blood progenitor cells (PBPC): first, the volume of the apheresis product is often large, requiring volume reduction prior to cryopreservation. Second, the platelet (PLT) loss due to the harvesting of the buffy coat is an unwanted side effect. With respect to these problems, the present study was designed to compare programs for PBPC collection with discontinous-flow cell separators. MATERIALS AND METHODS: Three different protocols for PBPC harvesting were investigated in 32 patients with malignancies. In the first protocol, the blood cell separator Haemonetics MCS 3p was used. In the second protocol using the same machine, the opening and closure of the stem cell valve was modified in combination with a centri surge to reduce the PLT loss. The MCS+ device with another configuration of the valves was used in the third protocol. PBPC were mobilised by chemotherapy plus cytokine administration or application of growth factor alone. Blood counts and CD34 antigen-expressing cells were determined before apheresis and in the PBPC product. Colony-forming unit granulocyte/macrophage (CFU-GM) were determined in the apheresis product. RESULTS: 55 PBPC collections were carried out with a median end product volume of 105 ml. The median counts for CD34+ antigen-expressing cells and CFU-GM were 1.5x10(6 )and 2.5x10(4)/kg body weight, respectively. PLT loss was significantly lower in protocol III. CONCLUSION: The study reported here revealed that PBPC could be easily collected in a reduced product volume by the intermittent-flow cell separators. No additional centrifugation prior to cryopreservation was necessary to remove the plasma from the apheresis product. Patient's PLT loss was reduced by the centri surge technique but this still has to be improved.
Asunto(s)
Células Madre Hematopoyéticas/citología , Leucaféresis/instrumentación , Anticoagulantes/metabolismo , Antígenos CD34/sangre , Recuento de Células Sanguíneas , Ácido Cítrico/metabolismo , Femenino , Glucosa/análogos & derivados , Glucosa/metabolismo , Hematócrito , Células Madre Hematopoyéticas/inmunología , Hemoglobinas/análisis , Humanos , Leucaféresis/métodos , Recuento de Leucocitos , Masculino , Factores de TiempoRESUMEN
We wished to test whether thrombopoietin (TPO) is entirely regulated by receptor binding or if other factors may play a role in the mechanism of TPO regulation. Therefore, we analyzed the TPO serum levels in 43 patients with reactive (secondary) thrombocytosis and in 37 with myeloproliferative thrombocytosis. Thrombocytosis was defined as a platelet level greater than 440 x 10(9)/l. Forty-two patients (98%) with reactive thrombocytosis had high concentrations of IL-6 correlating with elevated C-reactive protein levels. Twenty-three patients (53%) in this group had TPO serum concentrations of more than 300 pg/ml (normal: below 300 pg/ml). Only nine patients (24%) with myeloproliferative thrombocytosis had TPO serum levels above normal range, whereas 28 patients (76%) had normal levels of TPO. No correlation between the TPO serum levels and the concentrations of IL-6 or EPO was established. The other investigated thrombopoietic cytokines (IL-3, IL-11, GM-CSF) were unmeasurable; therefore, a correlation could not be assessed. We conclude that TPO concentrations are not strictly inversely related to platelet count. TPO serum levels are elevated especially in a considerable percentage of patients with reactive thrombocytosis, arguing for the existence of additional mechanisms of TPO regulation.
Asunto(s)
Trastornos Mieloproliferativos/sangre , Trombocitosis/sangre , Trombopoyetina/sangre , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Factor Estimulante de Colonias de Granulocitos y Macrófagos/sangre , Humanos , Interleucina-11/sangre , Interleucina-3/sangre , Interleucina-6/sangre , Masculino , Persona de Mediana Edad , Recuento de Plaquetas , Trombocitosis/etiologíaRESUMEN
To identify prognostic factors alternative or additional to P-glycoprotein (Pgp), we studied the impact of the multidrug resistance-related protein (MRP), bcl-2 (flow cytometry), mutant p53 (single-strand conformation polymorphism), and heat-shock protein 27 (HSP27, Western blotting) in myeloid blasts obtained at the time of diagnosis in patients with de novo acute myeloid leukemia (AML). We collected bone marrow samples from untreated AML patients, prepared the cells as well as the cellular protein, and froze all the material. We then analyzed 20 patients who responded with complete remission (CR) and 20 patients who had blast persistence (BP). The purpose of the study was to determine whether leukemic blasts from patients with BP were more resistant to chemotherapy than those from patients with CR. There was no significant correlation between the expression of any of these proteins alone and treatment outcome in both groups studied. In contrast, there was a significant correlation between the coexpression of at least two of these proteins and response (p = 0.0298), which turned out to be a significant independent prognostic factor for treatment failure (p = 0.0329, relative risk = 1.5) according to multivariate analysis. We conclude that drug resistance in AML is multifactorial. Thus, coexpression of different resistance mechanisms may be responsible for the primary drug resistance in de novo AML.
Asunto(s)
Leucemia Mieloide/tratamiento farmacológico , Leucemia Mieloide/metabolismo , Proteínas de Neoplasias/biosíntesis , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/biosíntesis , Transportadoras de Casetes de Unión a ATP/biosíntesis , Enfermedad Aguda , Adulto , Anciano , Análisis de Varianza , Resistencia a Múltiples Medicamentos , Femenino , Proteínas de Choque Térmico/biosíntesis , Humanos , Leucemia Mieloide/diagnóstico , Masculino , Persona de Mediana Edad , Proteínas Asociadas a Resistencia a Múltiples Medicamentos , Mutación/genética , Valor Predictivo de las Pruebas , Pronóstico , Proteínas Proto-Oncogénicas c-bcl-2/biosíntesis , Inducción de Remisión , Proteína p53 Supresora de Tumor/biosíntesis , Proteína p53 Supresora de Tumor/genéticaRESUMEN
PURPOSE: CAMPATH-1H is a human immunoglobulin G1 (IgG1) anti-CD52 monoclonal antibody (MAb) that binds to nearly all B-cell and T-cell lymphomas. We report here the results of a multicenter phase II trial of CAMPATH-1H in patients with advanced, low-grade non-Hodgkin's lymphoma (NHL) who were previously treated with chemotherapy. PATIENTS AND METHODS: Fifty patients who had relapsed (n=25) after or were resistant (n = 25) to chemotherapy were treated with CAMPATH-1H 30 mg administered as a 2-hour intravenous (i.v.) infusion three times weekly for a maximum period of 12 weeks. RESULTS: Six patients (14%) with B-cell lymphomas achieved a partial remission (PR). Patients with mycosis fungoides appeared to respond more frequently (50%; four of eight patients, which included two complete remissions [CRs]). Lymphoma cells were rapidly eliminated from blood in 16 of 17 patients (94%). CR in the bone marrow was obtained in 32% of the patients. Lymphoma skin lesions disappeared completely in four of 10 patients and partial regression was obtained in three patients. Lymphadenopathy and splenomegaly were normalized in only 5% and 15% of patients, respectively. Lymphopenia (< 0.5 x 10(9)/L) occurred in all patients. World Health Organization (WHO) grade IV neutropenia occurred in 14 patients (28%). Opportunistic infections were diagnosed in seven patients and nine patients had bacterial septicemia. Death related to infectious complications occurred in three patients. CONCLUSION: CAMPATH-1H had a significant but limited activity in patients with advanced, heavily pretreated NHL. The most pronounced effects were noted in the blood and bone marrow and in patients with mycosis fungoides. The risk for serious infectious complications needs to be considered for severely ill patients who are evaluated for CAMPATH-1H treatment.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Antineoplásicos/uso terapéutico , Antineoplásicos/uso terapéutico , Linfoma no Hodgkin/terapia , Adulto , Alemtuzumab , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales Humanizados , Anticuerpos Antineoplásicos/administración & dosificación , Anticuerpos Antineoplásicos/efectos adversos , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Esquema de Medicación , Femenino , Humanos , Infusiones Intravenosas , Linfoma de Células B/terapia , Masculino , Micosis Fungoide/terapia , Inducción de RemisiónRESUMEN
In 1994 the International Lymphoma Study Group (ILSG) published the "Revised European-American Classification of Lymphoid Neoplasms" (R.E.A.L. Classification). Lymphomas were classified according to their presumed normal counterparts, to the extent possible. Within both T- and B-cell categories differentiation between lymphomas and/or leukemias of "precursor" or "peripheral" neoplasms are defined arising from antigen independend or antigen reactive cell proliferation. Lymphomas undoubtedly characterized by currently available morphologic, immunologic, and genetic technics represent "real" disease entities. Provisional categories include lymphomas that have been described in some detail, but without consensus within the ILSG. Proposed names are based predominantly on established usage. With respect to similar treatment approaches and difficulties of the ILSG members in subclassifying large cell lymphomas, centroblastic, immunoblastic and large cell anaplastic lymphomas of B-cell type were "lumped" together as large B-cell lymphomas. Within a prospective treatment trial overall survival was significantly better in centroblastic as compared to B-cell immunoblastic lymphoma diagnosed by optimal histomorphology according the criteria of the Kiel Classification. Thus the R.E.A.L. Classification fails to identify patients who may require other than standard treatment. Future studies will demonstrate whether subclassifying the proposed "peripheral" T-cell lymphomas, unspecified into T-zone lymphoma, lymphoepitheloid (Lennert's) lymphoma and pleomorphic, small, medium, and large cell lymphomas according the Kiel Classification is of clinicopathologic relevance. On the contrary the subtypes of chronic lymphocytic leukemia of T-cell type form two distinct entities within the R.E.A.L. Classification separating T-CLL/prolymphocytic leukemia from large granular lymphocyte leukemia of T- and NK-cell type. Within the R.E.A.L. Classification the lymphoplasmacytoid immunocytoma of the Kiel Classification will be subsumed together with the prognostically significantly better B-cell chronic lymphocytic leukemia. Opposite to the original intention of the ILSG two proposals are developed on clinical grouping of entities. Clinical indolent lymphoid neoplasms usually have "low grade" histologic appearances, with a predominance of small cells subsuming with the exception of the mantle cell lymphoma all of the low grade lymphomas of the Kiel classification. Aggressive lymphomas (intermediate risk) are defined as tumors whose survival if untreated is measured in months, highly or very aggressive lymphomas and/or leukemias will kill untreated patients within weeks. Unlike the Kiel Classification proposed categories subsume lymphomas irrespective of cytomorphology, thus grouping together potentially curable and uncurable diseases. Undoubtedly the R.E.A.L. Classification forms at present the best compilation of existing knowledge upon neoplasms of the immune system, enabling cooperation between clinicians and scientists all over the world. According to the ILSG this proposal should be considered a starting point for future periodic reevaluations.
Asunto(s)
Linfoma no Hodgkin/clasificación , Europa (Continente) , Humanos , Linfoma de Células B/clasificación , Linfoma de Células B/diagnóstico , Linfoma de Células B/patología , Linfoma no Hodgkin/diagnóstico , Linfoma no Hodgkin/patología , Linfoma de Células T/clasificación , Linfoma de Células T/diagnóstico , Linfoma de Células T/patología , Estadificación de Neoplasias , Pronóstico , Estados UnidosRESUMEN
BACKGROUND: A rare multi-organ involvement in plasma-cell dyscrasias has been named POEMS-syndrome: it is a synopsis of monoclonal gammopathy (M-gradient), osteosclerotic bone lesions, peripheral polyneuropathy, organomegaly, endocrinopathy and skin lesions. CASE REPORT: A patient is presented who had a classical manifestation of this disease known mainly in Japan. A monoclonal IgA-lambda-gammopathy was determined as cause of a gradually progressive polyneuropathy. The patient had a hypergonadotropic hypogonadism, hyperprolactinaemia, and sclerotic bone lesions. In addition, he showed a changing organomegaly, and hyperpigmentation of the skin. CONCLUSION: As yet, aetiology and pathophysiology are not fully understood. Irradiation or surgical resection of one or several osteosclerotic bone lesions may improve the polyneuropathy or may even lead to a complete remission of all symptoms. Thus, monoclonal immunoglobulins should be searched for in any unclear polyneuropathy, as should be for other symptoms of the POEMS-syndrome.
Asunto(s)
Síndrome POEMS/diagnóstico , Diagnóstico Diferencial , Diagnóstico por Imagen , Humanos , Inmunoglobulina A/sangre , Cadenas lambda de Inmunoglobulina/sangre , Masculino , Persona de Mediana Edad , Huesos Pélvicos/patologíaAsunto(s)
Leucemia de Células Pilosas/diagnóstico , Leucemia Linfocítica Crónica de Células B/diagnóstico , Antineoplásicos Alquilantes/uso terapéutico , Clorambucilo/uso terapéutico , Humanos , Inmunofenotipificación , Leucemia Linfocítica Crónica de Células B/genética , Leucemia Linfocítica Crónica de Células B/terapiaAsunto(s)
Leucemia de Células Pilosas/diagnóstico , Leucemia Linfocítica Crónica de Células B/diagnóstico , Clorambucilo/uso terapéutico , Terapia Combinada , Humanos , Interferón-alfa/uso terapéutico , Leucemia de Células Pilosas/terapia , Leucemia Linfocítica Crónica de Células B/terapia , Cuidados Paliativos , PronósticoRESUMEN
Among high-grade malignant non-Hodgkin's lymphomas the updated Kiel classification identifies three major B-cell entities: centroblastic (CB), B-immunoblastic (B-IB), and B-large cell anaplastic (Ki-1+) (now termed anaplastic large cell [CD30+], [B-ALC]). The clinical prognostic relevance of this distinction was evaluated in a randomized prospective treatment trial (COP-BLAM/IMVP-16 regimen randomly combined +/- radiotherapy in complete responders) conducted in adult (age 15 to 75) patients with Ann Arbor stage II-IV disease (n = 219) diagnosed by optimal histomorphology (Giemsa staining) and by immunohistochemistry. Overall survival was significantly better in CB lymphoma as compared to B-IB (P = .0002) or B-ALC (P = .046). Relapse-free survival was worse for B-IB (P = .0003) as compared to CB lymphomas. The prognostic differences between CB and B-IB were confirmed by multivariate analyses including the risk factors of the International Index. Overall survival was significantly determined by performance status (P = .0003), serum-LDH (P = .036), and B-IB histology subtype (P = .036). Relapse-free survival was influenced by age (P = .007) and histological subtype (P = .007). Thus, the diagnosis of the CB and B-IB lymphomas by the histological criteria of the Kiel classification was identified as an independent prognostic factor in diffuse large B-cell lymphomas.