RESUMEN
In the perspective of increasing the clinical potential of ricin A chain immunotoxins (RTA-ITs), perhexiline (Pex) and four structural analogues (Pex 2, Pex 3, Pex 7, and Pex 11) were evaluated for their ability to enhance RTA-IT activity in vitro. Only perhexiline significantly enhanced the cytotoxic activity of anti-CD5 RTA-ITs, T101 and T101-F(ab')2, on CEM III cell line (30- to 2000-fold), and of anti-HLA-DR RTA-IT, HNC-241, on both RAJI cell line (greater than 100-fold) and two immortalized cell lines originating from patients suffering from B-cell chronic lymphocytic leukemia, EHEB and FS2 D5 (10-fold). On 16 consecutive fresh B-cell chronic lymphocytic leukemia cell samples, significant T101-F(ab')2 RTA-IT and HNC-241 RTA-IT enhancement was observed with perhexiline which was comparable to that of NH4Cl and monensin. Perhexiline almost completely blocked RTA-IT intracellular degradation and profoundly modified its routing. These observations were linked to perhexiline-induced lipidosis via inhibition of sphingomyelinase activity. In conclusion, since the concentrations used are relevant with the pharmacokinetics of this agent, perhexiline appears to be a promising agent for in vivo enhancement of ricin A chain immunotoxins.
Asunto(s)
Inmunotoxinas/farmacología , Leucemia Linfocítica Crónica de Células B/patología , Perhexilina/farmacología , Ricina/farmacología , Células Tumorales Cultivadas/efectos de los fármacos , Cloruro de Amonio/farmacología , Anticuerpos Monoclonales , Línea Celular , Humanos , Cinética , Leucemia Linfocítica Crónica de Células B/sangre , Monensina/farmacología , Proteínas de Neoplasias/biosíntesis , Perhexilina/análogos & derivados , Células Tumorales Cultivadas/citología , Células Tumorales Cultivadas/ultraestructura , Verapamilo/farmacologíaRESUMEN
In clinical practice, sensitivity of malignant cells to a given immunotoxin remains hypothetical, since standard test systems such as the protein synthesis inhibition assay or the cloning assay are not appropriate. This study evaluated the feasibility of a semi-routine procedure based on dye exclusion assay enumerating the percentage of living cells after fluorescein diacetate-propidium iodide staining. The validity of the method was evaluated using five different subclones derived from the CEM cell line, which expressed a wide range of sensitivity to T101 A-chain immunotoxin. The comparison between dye exclusion assay and standard test systems suggested that this method might allow an easy and reproducible semi-quantitative evaluation of the sensitivity of leukemia cells. In a series of 21 patients suffering from various blood diseases in which the malignant cells expressed the T65 antigen, dye exclusion assay could detect clear T101 immunotoxin cell sensitivity in about 50% of the cases. The mean density of T65 antigen on malignant cells was found to influence dramatically the sensitivity of target cells to T101 immunotoxin.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Antígenos de Neoplasias/inmunología , Leucemia/terapia , Ricina/administración & dosificación , Anticuerpos Antineoplásicos/inmunología , Permeabilidad de la Membrana Celular , Supervivencia Celular , Colorantes , Relación Dosis-Respuesta a Droga , Humanos , Técnicas In Vitro , Leucemia/patología , Proteínas de Neoplasias/biosíntesisRESUMEN
The normal counterparts of the B cells found in hairy cell leukemia (HCL) are not known. We report here a detailed morphological, cytochemical, immunological and molecular analysis of a patient with B-cell chronic lymphocytic leukemia (B-CLL) who later in the course of his disease developed hairy cell leukemia. We speculate that hairy cell transformation of B-CLL might be related to an in vivo protein kinase C mediated cellular activation of B-CLL cells.
Asunto(s)
Leucemia de Células Pilosas/patología , Leucemia Linfocítica Crónica de Células B/patología , Southern Blotting , Deleción Cromosómica , Cromosomas Humanos Par 14 , Reordenamiento Génico , Humanos , Cadenas Pesadas de Inmunoglobulina/genética , Inmunofenotipificación , Leucemia Linfocítica Crónica de Células B/complicaciones , Leucemia Linfocítica Crónica de Células B/genética , Masculino , Persona de Mediana Edad , Polimorfismo de Longitud del Fragmento de RestricciónRESUMEN
We compared the cell killing potency of a whole Ig ricin A-chain immunotoxin (T101 IgG-RTA) against its Fab fragment counterpart (T101 Fab-RTA) on both CEM cells and fresh malignant lymphoid cells. A dye exclusion assay (DEA), was used to evaluate the kinetics of leukaemia cell viability mediated in vitro by each immunotoxin (IT). This study found that in the absence of ammonium chloride (NH4Cl), used as an enhancer agent, T101 Fab-RTA was significantly more toxic to both CEM and fresh leukaemia cells than T101 IgG-RTA. In the presence of NH4Cl (10(-2) M), while no differences could be found between the two IT on CEM cells, T101 Fab-RTA was clearly superior to T101 IgG-RTA on fresh leukaemia cells. These results suggest that T101 Fab-RTA may offer an excellent alternative to T101 IgG-RTA for IT treatment of CD5 positive leukaemia patients.
Asunto(s)
Inmunotoxinas/uso terapéutico , Leucemia/terapia , Ricina/administración & dosificación , Cloruro de Amonio/administración & dosificación , Supervivencia Celular , Células Madre Hematopoyéticas/efectos de los fármacos , Humanos , Fragmentos Fab de Inmunoglobulinas/administración & dosificación , Inmunoglobulina G/administración & dosificación , Técnicas In Vitro , Leucemia de Células B/terapia , Relación Estructura-Actividad , Células Tumorales CultivadasRESUMEN
To optimize the immunohistochemical detection of the multidrug resistance (MDR)-associated P-glycoprotein (P-gp) in chronic lymphoid disorders, the authors compared the sensitivity of three different monoclonal antibodies (MoAb) directed against P-gp (C219, JSB-1, and MRK 16) by using the APAAP technique on four tissue preparations obtained from lymphoid tumors: Cryostat sections, ModAMEX processed sections, frozen cytospin preparations, and fresh cytospin preparations. Tumor samples were obtained from patients with previously treated chronic lymphocytic leukemia (6 cases) or non-Hodgkin's malignant lymphoma (4 cases). Lymph nodes (n = 9), spleen (n = 3), and blood (n = 5) were analyzed. JSB-1 MoAb detected P-gp in 4 of 12 cases (33.3%) on either frozen sections or ModAMEX processed sections, and in 6 of 17 cases (35.3%) on frozen cytospin preparations. The sensitivity of JSB-1 was significantly improved when fresh cytospin preparations were used with an incidence of P-gp positive samples as high as 70.6% (P < .05). C219 MoAb was unreactive with lymphoid cells whatever the technique used, whereas this antibody stained stromal cells. MRK 16 MoAb was equally reactive to JSB-1 on fresh cytospin preparations, but unreactive when the other preparations were used. The specificity of JSB1 MoAb was confirmed by both Western blot analysis and Rhodamine 123 efflux assay. The authors used JSB-1 MoAb on fresh cytospin smears prepared from 28 CLL patients. Overall incidence of P-gp positive cases was 39.2%. Univariate analysis showed that P-gp expression was correlated with prior therapy, refractoriness to treatment, Rai stratification, and time of tissue storage after diagnosis. The authors recommend the use of JSB-1 on fresh cytospin preparations for the immunocytochemical detection of P-gp in chronic lymphoid disorders.
Asunto(s)
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/análisis , Anticuerpos Monoclonales , Leucemia Linfocítica Crónica de Células B/sangre , Linfoma no Hodgkin/química , Especificidad de Anticuerpos , Criopreservación , Humanos , Inmunohistoquímica , Ganglios Linfáticos , Estudios Prospectivos , Sensibilidad y Especificidad , Manejo de Especímenes/métodos , BazoRESUMEN
A case of Richter's syndrome was investigated by several technics: light and electron microscopy, surface markers, immunohistological studies and immunoelectron microscopy. On light microscopy lymph node proliferation was composed of large lymphoid cells, some exhibiting Reed-Sternberg like features. On electron microscopy many intermediary cells, from small lymphocytes to immunoblasts and plasma cells, were noted. The circulating small lymphocytes were characterized as B cells (SIg +; MRBC+). The lymph node cells shared the same SIg phenotype (IgMK) but the percentage of MRBC was slightly lower. Immunohistological studies showed that lymph node cells were stained exclusively by anti micron and anti kappa antisera. These results are indicative of the B clonal origin of the two cell proliferations. Immunoelectron microscopy showed three staining patterns: 1) cells presenting only surface staining, 2) cells with diffuse staining presumably related to ribosomal fixation, 3) cells with endoplasmic reticulum staining. The significance of these three patterns is discussed with regard to B lymphocyte differentiation.
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Linfocitos B/inmunología , Leucemia Linfoide/patología , Linfoma no Hodgkin/patología , Receptores de Antígenos de Linfocitos B/inmunología , Anciano , Células Clonales , Humanos , Leucemia Linfoide/inmunología , Linfocitos/inmunología , Linfoma no Hodgkin/inmunología , Masculino , Microscopía Electrónica , Células Plasmáticas/inmunología , Coloración y Etiquetado , SíndromeRESUMEN
The 5 q deletion is frequently found in myelodysplastic syndromes and acute non lymphoid leukemia, but this anomaly is usually found in secondary diseases and associated with many other chromosomal aberrations. This report describes four cases of "de novo" acute leukemia with a sole 5q- anomaly. They had no cytological, genetic or clinical characteristics of secondary disorders. It is important to note that of the four patients studied, three had proliferation of immature blast cells. One case was classified as a MO AML and two as "undifferentiated" acute leukemia. Furthermore, these four cases of acute leukemia showed a deletion of the same portion of the long arm of chromosome 5: q22q33. On the same part of this chromosome many hematopoietic growth factor genes have been located, like IL3 and GM-CSF which have early undifferentiated hematopoietic stem cells as a their target.
Asunto(s)
Deleción Cromosómica , Cromosomas Humanos Par 5 , Leucemia/genética , Enfermedad Aguda , Anciano , Femenino , Humanos , Inmunofenotipificación , Cariotipificación , Leucemia/inmunología , Leucemia/patología , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Using a leucocyte migration test (Clausen's direct agarose gel migration method) hypersensitivity to human encephalitogenic protein has been examined in 50 multiple sclerosis patients (group 1), 50 healthy persons (group 2) and 25 patients with other neurological diseases (group 3). In group 1, 30 MS patients (60%) show an abnormal migration index, manifested either as inhibition or stimulation of migration; 29 controls in group 2 (58%), 11 O.N.D. patients in group 3 (44%) show an abnormal migration index. These results mean that lymphocyte hypersensitivity to myelin basic protein appears neither to be constant nor specific to multiple sclerosis. Three migration index curve types at different antigen concentration are obtained: monophasic curves within the normal index zones; monophasic curves staying in the inhibition or stimulation zone and biphasic curves with dose-effect relationship. Whatever the antigen used, this dose-effect relationship implies that the test must be carried out at different concentrations. The meaning of spontaneous sensitisation in healthy controls is discussed.
Asunto(s)
Hipersensibilidad Tardía/complicaciones , Linfocitos/inmunología , Esclerosis Múltiple/complicaciones , Proteína Básica de Mielina/inmunología , Adolescente , Adulto , Factores de Edad , Inhibición de Migración Celular , Movimiento Celular , Relación Dosis-Respuesta Inmunológica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sefarosa , Factores SexualesRESUMEN
22q11.2 deletion is a common genetic disorder characterised by a wide spectrum of clinical manifestations. To date no simple genotype-phenotype correlation has been established. Moreover, several reports have mentioned phenotypic discordance between monozygotic twins. No definite mechanism has been demonstrated and mosaicism, a postzygotic second hit, environmental effects and chance events have been proposed. The twinning process itself has been suspected in two cases (11, 23). We report the case of monozygous twins with a 22q11.2 deletion who are discordant for a heart defect. We found no arguments for mosaicism or twin-to-twin transfusion syndrome. The frequent discordance for heart defects in DiGeorge/Velo-cardio-facial syndromes (DGS/VCFS) does not favour the hypothesis of somatic mutations contributing to the phenotypic variation, but rather a complex interaction between genetic and environmental systems.
Asunto(s)
Deleción Cromosómica , Cromosomas Humanos Par 22 , Síndrome de DiGeorge/genética , Enfermedades en Gemelos/genética , Fenotipo , Insuficiencia Velofaríngea/genética , Anomalías Múltiples/diagnóstico , Anomalías Múltiples/genética , Adulto , Coartación Aórtica/diagnóstico , Coartación Aórtica/genética , Síndrome de DiGeorge/diagnóstico , Facies , Femenino , Retardo del Crecimiento Fetal/diagnóstico , Retardo del Crecimiento Fetal/genética , Variación Genética , Genotipo , Humanos , Hibridación Fluorescente in Situ , Recién Nacido , Embarazo , Gemelos Monocigóticos/genética , Insuficiencia Velofaríngea/diagnósticoRESUMEN
UNLABELLED: Diagnosis of inflammatory non-infectious diseases with a neonatal onset is often retrospective. It may lead to aggressive and iatrogenic procedures. PATIENT: A 6-year-old boy was suffering, since birth, from recurrent febrile attacks including rashes, gastrointestinal manifestations and inflammatory joint involvement. This syndrome, partially improved with steroids, could have been of antenatal onset. Since the age of 4 years, the patient is considered as having hyper-IgD syndrome (HIDS). DISCUSSION: HIDS must be distinguished from familial Mediterranean fever. Patients suffer from recurrent fever concomitant to inflammatory joint involvement, abdominal distress, skin lesions, swollen lymph nodes and hepatosplenomegaly (especially seen in children). All patients have high serum IgD (> 100 UI/mL) and IgA levels. Nevertheless, a high IgD level is not specific. Our case could also be part of the CINCA (chronic, infantile, neurological, cutaneous and articular) syndrome, which includes similar early manifestations associated with a constant neurological and frequent ophthalmological involvement and epiphyseal changes; to date, these last three manifestations are not present in our patient. CONCLUSION: HIDS and CINCA syndrome are not known to be modified by any effective therapeutic agent. When presenting at birth, these inflammatory diseases must be considered as entities with a rarely described potential severity.
Asunto(s)
Fiebre Mediterránea Familiar/complicaciones , Hipergammaglobulinemia/complicaciones , Inmunoglobulina D , Antiinflamatorios/uso terapéutico , Artritis/complicaciones , Niño , Diagnóstico Diferencial , Exantema/complicaciones , Fiebre Mediterránea Familiar/congénito , Glucocorticoides/uso terapéutico , Humanos , Hipergammaglobulinemia/congénito , Inmunoglobulina A/sangre , Inmunoglobulina D/sangre , Masculino , Prednisona/uso terapéutico , SíndromeRESUMEN
Background: Minimal residual disease (MRD) assessment provides a powerful prognostic factor for therapeutic stratification in acute lymphoblastic leukemia (ALL). Multiparameter flow cytometry (MFC) has the potential for a rapid and sensitive identification of high risk patients. Our group has previously published that MRD levels analyzed by clone specific Ig/TcR-QPCR and MFC were concordant at a sensitivity of 10-4 . Here we report the MFC methodological aspects from this multi-center experience. Methods: MRD was assessed by MFC in 1030 follow-up samples from 265 pediatric and adult patients with de novo ALL treated in the FRALLE, EORTC or GRALL clinical trials. MRD assessment as applied by the eight participating MFC laboratories is described in detail regarding cell preparation, leukemia-associated immunophenotype (LAIP) markers and data analysis. Samples were obtained from bone marrow (BM) and peripheral blood (PB). Immunostaining was performed after erythrocyte lysis or Ficoll enrichment. Results: This study confirms the applicability of MFC-based MRD assessment in 97% of patients with ALL at the 10-4 cut-off. MRD values after Ficoll enrichment and erythrocyte lysis were found comparable. Higher MRD values were obtained in BM than in PB, especially for B-lineage ALL. Conclusions: Measurement of MRD by MFC at the 10-4 cut-off is applicable within a few hours for almost all patients and using a comparable analytical strategy allows for multicenter collaborative studies. The method can be introduced in a strategy aimed at defining the risk of failure of patients with childhood or adult ALL. © 2014 Clinical Cytometry Society.
RESUMEN
Minimal residual disease (MRD) quantification is widely used for therapeutic stratification in pediatric acute lymphoblastic leukemia (ALL). A robust, reproducible, sensitivity of at least 0.01% has been achieved for IG/TCR clonal rearrangements using allele-specific quantitative PCR (IG/TCR-QPCR) within the EuroMRD consortium. Whether multiparameter flow cytometry (MFC) can reach such inter-center performance in ALL MRD monitoring remains unclear. In a multicenter study, MRD was measured prospectively on 598 follow-up bone marrow samples from 102 high-risk children and 136 adult ALL patients, using IG/TCR-QPCR and 4/5 color MFC. At diagnosis, all 238 patients (100%) had at least one suitable MRD marker with 0.01% sensitivity, including 205/238 samples (86%) by using IG/TCR-QPCR and 223/238 samples (94%) by using MFC. QPCR and MFC were evaluable in 495/598 (83%) samples. Qualitative results (<0.01% or ≥0.01%) concurred in 96% of samples and overall positivity (including <0.01% and nonquantifiable positivity) was concurrent in 84%. MRD values ≥0.01% correlated highly (r(2)=0.87) and 69% clustered within half-a-log(10). QPCR and MFC can therefore be comparable if properly standardized, and are highly complementary. MFC strategies will benefit from a concerted approach, as does molecular MRD monitoring, and will contribute significantly to the achievement of 100% MRD informativity in adult and pediatric ALL.
Asunto(s)
ADN de Neoplasias/genética , Reordenamiento Génico , Genes de Inmunoglobulinas/genética , Genes Codificadores de los Receptores de Linfocitos T/genética , Neoplasia Residual/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Adulto , Niño , Preescolar , Femenino , Citometría de Flujo , Estudios de Seguimiento , Humanos , Lactante , Masculino , Neoplasia Residual/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Pronóstico , Estudios Prospectivos , Sensibilidad y Especificidad , Tasa de SupervivenciaAsunto(s)
Leucemia Mieloide/genética , Poliploidía , Enfermedad Aguda , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Aberraciones Cromosómicas , Análisis Citogenético , Femenino , Humanos , Cariotipificación , Leucemia Mieloide/diagnóstico , Leucemia Mieloide/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Polimorfismo Genético , Estudios Retrospectivos , Análisis de SupervivenciaRESUMEN
Thirty B-cell chronic lymphocytic leukemia patients were treated with fludarabine-cyclophosphamide-rituximab (FCR) and immune cell counts (natural killer (NK) cells, CD4, CD8, Tgammadelta and monocytes) were monitored from the end of treatment (EOT) up to 36 months (M36). Moreover, nonleukemic peripheral blood lymphocyte cytotoxicity (PBL/CTC) as well as rituximab (RTX)-dependent PBL/CTC was also measured at the initiation of therapy, EOT and M12. These parameters were correlated with post-FCR monitoring of the minimal residual disease (MRD) level in blood using a four-color flow cytometry technique. FCR induced a profound and sustained depletion of all T-cell populations, Tgammadelta being the most affected, whereas NK cells were relatively preserved. Both basal and interleukin-2-stimulated nonleukemic PBL/CTC against MEC-2, a CLL cell line, increased during the post-FCR period. There was no correlation between immune recovery parameters and MRD progression profile, except that patients with high post-FCR CD4(+) counts experienced rapid MRD progression. MRD at M12 predicts clinical relapse. The limited data show RTX-mediated LBL/CTC activity against autologous B-cell cells in individuals with <1% residual disease at M12, opening avenues for immunomodulation post-FCR with anti-CD20 antibodies. To conclude, our study suggests that MRD increase at M12 precedes disease evolution post-FCR, and should be assessed as a surrogate marker for proactive management of CLL relapse.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Inmunoterapia , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Leucemia Linfocítica Crónica de Células B/inmunología , Adulto , Anciano , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales de Origen Murino , Ciclofosfamida/administración & dosificación , Femenino , Citometría de Flujo , Estudios de Seguimiento , Humanos , Inmunomodulación , Células Asesinas Naturales/inmunología , Leucemia Linfocítica Crónica de Células B/patología , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/diagnóstico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/patología , Neoplasia Residual/diagnóstico , Neoplasia Residual/tratamiento farmacológico , Neoplasia Residual/patología , Pronóstico , Rituximab , Tasa de Supervivencia , Vidarabina/administración & dosificación , Vidarabina/análogos & derivadosRESUMEN
The DNA index (DI) is a prognostic factor in childhood acute lymphoblastic leukemia (ALL). The accuracy of DI measurement is important for treatment stratification: hyperdiploidy with DI > or = 1.16 is predictive of favorable prognosis whereas hypodiploidy is associated with poor prognosis. The aim of this study was to validate the accuracy of the DI measured by flow cytometry (FCM) by comparison with the karyotype. From samples of 112 childhood ALL, we created a formula to calculate a theoretical DNA index (tDI) based on the blast cell karyotype, taking into account the additional or missing chromosome material of the major clone. FCM DI correlated with tDI calculated from karyotype (R = 0.987) and with modal chromosome number (DI = 0.0202 x Modal NB + 0.0675 and R = 0.984). In three cases a hypodiploid blast cell population was detected by FCM, while only the duplicated clone was identified by the karyotype. The strong correlation between tDI and DI validates the accuracy of FCM quantification, which is technically fast on fresh or frozen samples. If the karyotype is essential to analyze chromosomal abnormalities, FCM provides complementary information in aneuploid ALLs, either by confirming the cytogenetic data or by detecting additional clones not identified when only using cytogenetic data.
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ADN/análisis , Citometría de Flujo/métodos , Cariotipificación/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Adolescente , Linfocitos B/inmunología , Linaje de la Célula , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Ploidias , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Pronóstico , Linfocitos T/inmunologíaRESUMEN
A new mutation of the CD40LG gene that encodes the CD40 ligand molecule was characterized in a young patient harboring a hyper-IgM with immunodeficiency syndrome. Inactivation of CD40LG gene resulted from the insertion of an AluYb8 element in exon 1 responsible for a total deficiency of CD40 ligand expression by T lymphocytes. Maternal transmission of the X-linked mutation was confirmed by gene-specific polymerase chain reaction. This is the 17th case report concerning a human genetic disease caused by an Alu element insertion in a coding sequence.
Asunto(s)
Elementos Alu/genética , Ligando de CD40/genética , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Síndrome de Inmunodeficiencia con Hiper-IgM Tipo 1/genética , Mutagénesis Insercional/genética , Secuencia de Bases , Cromosomas Humanos X/genética , Exones/genética , Humanos , Lactante , Masculino , Datos de Secuencia Molecular , MutaciónRESUMEN
BACKGROUND: Lymphocytopenia is a prognostic factor in Hodgkin's disease. In diffuse large B-cell lymphoma (DLBCL), data are much less established, in spite of numerous reports on immune system-lymphoma interactions. This study addresses the prognostic value of blood lymphocyte subsets at diagnosis in DLBCL. PATIENTS AND METHODS: Absolute values of blood lymphocyte subsets and monocytes were prospectively determined by flow cytometry in 140 patients with 2 or 3 adverse age-adjusted International Prognostic Index (aaIPI) factors included in a Groupe d'Etude des Lymphomes de l'Adulte protocol (LNH98B3). Absolute cell counts at diagnosis and aaIPI were evaluated with regard to clinical outcome. RESULTS: Low median cell counts of 337, 211, and 104/mul were evidenced for the CD4+, CD8+ T, and natural killer (NK) cells, respectively. In univariate analysis, only NK cell count [odds ratio (OR) = 1.81 (1.27, 2.57), P = 0.001] and aaIPI [OR = 2.29 (0.95, 5.45), P = 0.06] were associated with induction treatment response. Low NK cell count [Hazard ratio (HR) = 1.27 (1.06, 1.52), P = 0.01] and aaIPI 3 [HR = 1.95 (1.20, 3.16), P = 0.01] were also associated with a shorter event free survival (EFS). In multivariate analysis, NK cell count was associated with response [OR = 1.77 (1.24, 2.54), P = 0.002] and EFS [HR = 1.25 (1.04, 1.50) P = 0.02] independently of aaIPI. CONCLUSIONS: This study shows an association between circulating NK cell number and clinical outcome in DLBCL, possibly important in the context of the broadening use of rituximab, a likely NK-dependent therapy.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Células Asesinas Naturales/citología , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/inmunología , Linfopenia , Adulto , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales de Origen Murino , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Linfocitos B/citología , Bleomicina/administración & dosificación , Linfocitos T CD4-Positivos/citología , Linfocitos T CD8-positivos/citología , Recuento de Células , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Etopósido/administración & dosificación , Femenino , Citometría de Flujo , Humanos , Inmunofenotipificación , Estimación de Kaplan-Meier , Linfoma de Células B Grandes Difuso/mortalidad , Masculino , Persona de Mediana Edad , Monocitos/citología , Trasplante de Células Madre de Sangre Periférica , Rituximab , Resultado del Tratamiento , Vincristina/administración & dosificaciónRESUMEN
The authors have studied in particular hepatitis B virus markers and the ratio of OKT4+/OKT8+ cells in two subgroups of 52 deprived asymptomatic drug addicts. In the group 1 (deprived for 19 days on an average), 52% of the subjects showed a ratio of OKT4+/OKT8+ less than 1, whereas in the group 2 (deprived for 30 months on an average), this percentage is only of 25%. HBV markers were present in 90% of the subjects in each group. We would like to point out the high frequency of the anti-HBc positivity without other markers in these two groups, respectively 20% in the group 1 and 32% in the group 2. These results emphasize the interest in screening systematically this marker in all blood donors.
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Anticuerpos contra la Hepatitis B/análisis , Linfocitos/análisis , Trastornos Relacionados con Sustancias/inmunología , Adolescente , Anticuerpos Monoclonales/análisis , Donantes de Sangre , Femenino , Técnica del Anticuerpo Fluorescente , Humanos , Masculino , RiesgoRESUMEN
Using a case study of a blastic crisis supervening on chronic lymphocytic leukemia, we were able to determine that the cells in question were B cells derived from the same clone by using immunofluorescence and immunoperoxidase techniques. The immunoperoxidase technique provided excellent morphological details and enhanced the phenotype study.