RESUMEN
We designed a randomized trial of IC with or without quinine, an agent capable of reverting the multidrug resistance (mdr) phenotype, in patients aged < or = 65 years with high risk MDS. Patients were randomized to receive Mitoxantrone 12 mg/m2/d d2-5 + AraC 1 g/m2/12 h d1-5, with (Q+) or without (Q-) quinine (30 mg/kg/day). 131 patients were included. PGP expression analysis was successfully made in 91 patients and 42 patients (46%) had positive PGP expression. In PGP positive cases, 13 of the 25 (52%) patients who received quinine achieved CR, as compared to 3 of the 17 (18%) patients treated with chemotherapy alone (p = 0.02). In PGP negative cases, the CR rate was 35% and 49%, respectively in patients who received quinine or chemotherapy alone (difference not significant). In the 42 PGP positive patients, median Kaplan-Meier (KM) survival was 13 months in patients allocated to the quinine group, and 8 months in patients treated with chemotherapy alone (p = 0.01). In PGP negative patients, median KM survival was 14 months in patients allocated to the quinine group, and 14 months in patients treated with chemotherapy alone. Side effects of quinine mainly included vertigo and tinnitus that generally disappeared with dose reduction. Mucositis was significantly more frequently observed in the quinine group. No life threatening cardiac toxicity was observed. In conclusion, results of this randomized study show that quinine increases the CR rate and survival in PGP positive MDS cases treated with IC. The fact that quinine had no effect on the response rate and survival of PGP negative MDS suggests a specific effect on PGP mediated drug resistance rather than, for instance, a simple effect on the metabolism of Mitoxantrone and/or AraC.
Asunto(s)
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Genes MDR , Síndromes Mielodisplásicos/tratamiento farmacológico , Síndromes Mielodisplásicos/genética , Quinina/uso terapéutico , Adulto , Anciano , Anemia Refractaria con Exceso de Blastos/fisiopatología , Aberraciones Cromosómicas , Citarabina/administración & dosificación , Progresión de la Enfermedad , Femenino , Humanos , Cariotipificación , Leucemia Mieloide Aguda/fisiopatología , Masculino , Persona de Mediana Edad , Mitoxantrona/administración & dosificación , Síndromes Mielodisplásicos/mortalidad , Fenotipo , Inducción de Remisión , Análisis de SupervivenciaRESUMEN
Kikuchi's disease is rare necrotic histiocytosis of the lymph nodes. Since the first description in Japan in 1972 by Kikuchi, several cases have been reported. The disease occurs most frequently in young women. Manifestations include enlargement of the cervical lymph nodes, sometimes with fever, and often associated with other non-specific clinical signs. Blood chemistry, including immunologic tests, are often normal but neutropenia and raised erythrocyte sedimentation rate have been reported. Diagnosis relies on the histological examination of lymph node biopsies. Generally the clinical course is favourable in 3-4 months. Secondary systemic lupus erythomatosus may develop and require regular follow-up. The aetiology of this rare disease is still unclear although certain observations would favour an immunological process. Very rare in France, we report a case of Kikuchi's disease in a pregnant woman and present a review of the literature.
Asunto(s)
Linfadenitis/diagnóstico , Complicaciones del Embarazo , Adulto , Femenino , Histiocitos/patología , Humanos , Ganglios Linfáticos/patología , Linfadenitis/etiología , Linfadenitis/terapia , Cuello , Necrosis , EmbarazoRESUMEN
We report a case of spontaneous remission of lymphoid blast crisis in chronic myelogenous leukaemia (CML) which returned to chronic phase, without the use of cytostatic chemotherapy, following an episode of viral infection and blood transfusion. Although complete remissions of acute leukaemia have been described, this evolution is extremely rare and has never been reported in CML blast crisis. The role of hypothetical factors leading to such a rare event are briefly discussed.
Asunto(s)
Crisis Blástica/terapia , Transfusión Sanguínea , Leucemia Mielógena Crónica BCR-ABL Positiva/terapia , Virosis/complicaciones , Anciano , Femenino , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/complicaciones , Regresión Neoplásica EspontáneaRESUMEN
Karyotypic detection of chromosomal 16 abnormalities classically associated with AML M4Eo can be difficult. Characterization of the two genes involved in the inv(16)(p13q22), CBF beta and MYH11, has allowed the detection of fusion transcripts by reverse-transcriptase polymerase chain reaction (RT-PCR). We have analyzed CBF beta-MYH11 fusion transcripts by RT-PCR in myelomonocytic leukemias, with or without eosinophilia, to determine whether their presence correlates with morphology. Fifty-three cases (11 AML M4Eo; 1 AML M4 with atypical abnormal eosinophils (AML M4 "Eo"); 29 AML M4; 8 AML M5; 3 CMML; and 1 AML M2 with eosinophilia) were analyzed. All 11 typical AML M4Eo were CBF beta-MYH11 positive. The single case of AML M4 with distinctive eosinophil abnormalities was negative by karyotype, RT-PCR and fluorescent in situ hybridization (FISH). Three of 29 (10%) AML M4 without abnormal eosinophils were CBF beta-MYH11 positive, 1 of which did not show any apparent chromosome 16 abnormalities by classical metaphase analysis (2 not tested). Both cases tested also showed MYH11 genomic rearrangement. None of the other leukemias were RT-PCR positive. Follow-up of three patient showed residual positivity in apparent complete remission. These data show that CBF beta-MYH11 fusion transcripts occur not only in the vast majority of typical AML M4Eo, but also in approximately 10% of AML M4 without eosinophilic abnormalities, a much higher incidence than the sporadic reports of chromosome 16 abnormalities in AML M4 would suggest. Taken together with the detection of CBF beta-MYH11 transcripts in the absence of apparent chromosome 16 abnormalities by classical banding techniques, these data show that additional screening by either RT-PCR or FISH should be performed in all AML M4, regardless of morphologic features, to allow accurate evaluation of the prognostic importance of this fusion transcript.
Asunto(s)
Cromosomas Humanos Par 16/ultraestructura , Proteínas de Unión al ADN/genética , Eosinófilos/patología , Leucemia Mielomonocítica Aguda/genética , Miosinas/genética , Proteínas de Neoplasias/genética , Proteínas de Fusión Oncogénica/genética , ARN Mensajero/análisis , ARN Neoplásico/análisis , Factores de Transcripción/genética , Adolescente , Adulto , Anciano , Secuencia de Bases , Niño , Preescolar , Aberraciones Cromosómicas , Inversión Cromosómica , Subunidad alfa 1 del Factor de Unión al Sitio Principal , Factores de Unión al Sitio Principal , Femenino , Humanos , Lactante , Leucemia Mielomonocítica Aguda/clasificación , Leucemia Mielomonocítica Aguda/metabolismo , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa , Factor de Transcripción AP-2RESUMEN
Antigen-independent adhesion of resting adult CD4+ CD45RO+ T cells to B lymphocytes has been shown to be transient and can be down-regulated by CD4 major histocompatibility complex (MHC) class II molecule interactions. Conversely, adhesion of adult CD4+ CD45RA+ subpopulation to B cells is not regulated by ligands of CD4. We have investigated the regulation of adhesion of cord blood CD45RA+ CD4+ T lymphocytes. In contrast to adult CD45RA+ CD4+ T cells, cord blood CD45RA+ CD4+ T cells were strongly sensitive to the down-regulation of adhesion mediated by the CD4-HLA class II interaction, since adhesion to MHC class II(+) B cells was transient and inhibited by an anti-CD4 antibody. In addition, human immunodeficiency virus gp160, synthetic gp106-derived peptides encompassing a CD4 binding site inhibited conjugate formation between cord blood CD45RA+ CD4+ T cells and B cells. Following activation of the cord blood CD4 T cells by an anti-CD3 antibody, a conversion from a transient to a stable adhesion pattern of cord blood CD4 T cells to B cells occurred in 2 days. The reversal to a transient adhesion occurred at day 8 following anti-CD3 activation in correlation with a complete shift to a CD45RO phenotype of the cord blood CD4 T cells. These data suggest that CD4 T cell adhesion can be developmentally regulated.
Asunto(s)
Antígenos/fisiología , Antígenos CD4/análisis , Sangre Fetal/inmunología , Antígenos Comunes de Leucocito/análisis , Linfocitos T/fisiología , Adulto , Secuencia de Aminoácidos , Linfocitos B/inmunología , Antígenos CD4/fisiología , Adhesión Celular , Sangre Fetal/citología , Productos del Gen env/farmacología , Proteínas gp160 de Envoltorio del VIH , Antígenos de Histocompatibilidad Clase II/análisis , Humanos , Activación de Linfocitos , Datos de Secuencia Molecular , Precursores de Proteínas/farmacología , Linfocitos T/inmunologíaRESUMEN
Therapeutic options for treatment of recurrence of leukaemia after allogeneic bone marrow transplantation (BMT) are limited. A beneficial effect of donor lymphocyte infusions (DLI) has not previously been described in acute myeloid leukaemia (AML) relapse. We report a case of AML with t(8;21), relapsing 3 months after BMT, who received DLI without adjuvant chemotherapy or growth factors. The patient developed acute GVHD and achieved a rapid complete remission of his AML by both cytologic and molecular criteria of at least 14 months duration, thereby showing that DLI for AML in relapse after BMT is an alternative therapeutic option.
Asunto(s)
Trasplante de Médula Ósea , Leucemia Mieloide Aguda/terapia , Transfusión de Leucocitos , Proteínas Proto-Oncogénicas , Adulto , Clonación Molecular , Terapia Combinada , Subunidad alfa 2 del Factor de Unión al Sitio Principal , Proteínas de Unión al ADN/genética , Humanos , Masculino , Proteínas de Neoplasias/genética , Reacción en Cadena de la Polimerasa , Proteína 1 Compañera de Translocación de RUNX1 , Recurrencia , Factores de Transcripción/genéticaRESUMEN
We have developed a simplified fluorescent run-off (FluRO) based IgH PCR strategy in order to facilitate follow-up of large numbers of B-cell precursor (BCP) acute lymphoblastic leukaemias (ALL) in a routine molecular diagnostic laboratory. DNA samples from 26 BCP-ALL and one B-cell line were amplified using IgH FR1 and FR2 consensus primers and analysed in parallel either by ethidium bromide non-denaturing PAGE or, after rendering the PCR products fluorescent with an internal JH consensus primer, by high-resolution analysis on an automated fragment analyser. The latter led to a minimum of one log increase in sensitivity of detection in 62% of alleles from 19 samples (16/28 in FR1; 11/15 in FR2) tested in parallel on log DNA dilutions, and to at least a 10(-2) level of sensitivity of detection in 15/19. The improved resolution allowed an approximate 20% increase in the number of clonal alleles detected, and consequently doubled the incidence of oligoclonality (6/26; 23%). Using these strategies, 6/17 (35%) of children analysed prospectively showed residual IgH positivity in the post induction complete remission bone marrow sample. Both early deaths occurred within this subgroup of patients and of the three of four surviving patients tested, two remained positive 2-3 months later. Although this simplified strategy is, as expected, less sensitive than anti-V-D-J junction specific strategies, it enables detection of a category of 'slow-remitters' which may have prognostic significance at a stage where therapeutic decisions are taken.
Asunto(s)
Linfoma de Burkitt/diagnóstico , Reordenamiento Génico de Cadena Pesada de Linfocito B , Neoplasia Residual/diagnóstico , Fluorescencia , Humanos , Reacción en Cadena de la Polimerasa , Sensibilidad y Especificidad , Células Tumorales CultivadasRESUMEN
Although recurrent malignancy is the most frequent indication for second stem cell transplantation (2nd SCT), there are few reports that include sufficiently large numbers of patients to enable prognostic factor analysis. This retrospective study includes 150 patients who underwent a 2nd SCT for relapsed acute myeloblastic leukaemia (n = 61), acute lymphoblastic leukaemia (n = 47) or chronic myeloid leukaemia (n = 42) after a first allogeneic transplant (including 26 T-cell-depleted). The median interval between the first transplant and relapse, and between relapse and second transplant was 17 months and 5 months respectively. After the 2nd SCT, engraftment occurred in 93% of cases, 32% of patients developed acute graft-vs.-host disease (GVHD) >/= grade II and 38% chronic GVHD. The 5-year overall and disease-free survival were 32 +/- 8% and 30 +/- 8%, respectively, with a risk of relapse of 44 +/- 12% and a transplant-related mortality of 45 +/- 9%. In a multivariate analysis, five factors were associated with a better outcome after 2nd SCT: age < 16 years at second transplant; relapse occurring more than 12 months after the first transplant; transplantation from a female donor; absence of acute GVHD; and the occurrence of chronic GVHD. The best candidates for a second transplant are likely to be patients with acute leukaemia in remission before transplant, in whom the HLA-identical donor was female and who relapsed more than 1 year after the first transplant.