RESUMEN
Between 2007 and 2013, 13 children diagnosed with primary mediastinal large B-cell lymphoma (PMLBL) were treated according to a modified version of AIEOP (Associazione Italiana Ematologia Oncologia Pediatrica) LNH-97 protocol based on high-dose methotrexate, anthracyclines, and addition of anti-CD20. Ten patients achieved a continuous complete remission with front-line therapy. The overall 5-year survival was 91.7%, and event-free survival was 83.9%, with only one patient dying of progressive disease. Despite the few cases, these results demonstrate that this therapy, which includes anti-CD20, given in a multicenter setting, is feasible with acceptable toxicity in children with PMLBL.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Linfoma de Células B/tratamiento farmacológico , Linfoma de Células B/mortalidad , Neoplasias del Mediastino/tratamiento farmacológico , Neoplasias del Mediastino/metabolismo , Adolescente , Niño , Citarabina/administración & dosificación , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Metotrexato/administración & dosificación , Estudios Retrospectivos , Rituximab/administración & dosificación , Tasa de SupervivenciaAsunto(s)
Formación de Anticuerpos , Linfoma Anaplásico de Células Grandes/inmunología , Neoplasia Residual/diagnóstico , Proteínas Tirosina Quinasas/inmunología , Adolescente , Quinasa de Linfoma Anaplásico , Anticuerpos/sangre , Niño , Preescolar , Humanos , Lactante , Cinética , Linfoma Anaplásico de Células Grandes/diagnóstico , Linfoma Anaplásico de Células Grandes/tratamiento farmacológico , Neoplasia Residual/inmunología , Proteínas Nucleares/inmunología , Nucleofosmina , Proteínas de Fusión Oncogénica/inmunología , Proteínas Tirosina Quinasas ReceptorasRESUMEN
Hb Villejuif [beta123(H1)Thr-->Ile] is a silent and asymptomatic variant described in 1989 in an 87-year-old woman of French origin suffering from coincidental polycythemia vera. This paper reports the second observation of Hb Villejuif in three related subjects from Montesarchio, Southern Italy. All routine techniques for hemoglobin analysis yielded normal results with the exception of a slight increase in the Hb A2 value. The occurrence of a variant beta-globin was rapidly assessed by liquid chromatography mass spectrometric analysis and the abnormal chain purified by high performance liquid chromatography. The amino acid replacement Thr-->Ile at beta123 was determined by tandem electrospray mass spectrometric analysis of the tryptic digest of the variant beta chain. The corresponding DNA mutation was established as C-->T at the second position of codon 123 (ACC-->ATC) by polymerase chain reaction amplification techniques.
Asunto(s)
Hemoglobinas Anormales/análisis , Adulto , Secuencia de Aminoácidos , Sustitución de Aminoácidos , Niño , Preescolar , Cromatografía Líquida de Alta Presión , Codón/genética , Análisis Mutacional de ADN , Diagnóstico Diferencial , Femenino , Globinas/genética , Haplotipos/genética , Hemoglobinas Anormales/genética , Humanos , Italia/epidemiología , Masculino , Espectrometría de Masas , Datos de Secuencia Molecular , Mutación Missense , Linaje , Policitemia Vera/sangre , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Talasemia beta/diagnósticoRESUMEN
A high oxygen affinity hemoglobin variant was identified in a 53-year-old male patient from Napoli (Italy), suffering from pulmonary thromboembolism and polycythemia. A detailed structural characterization of the variant hemoglobin was carried out, both at the protein and DNA levels, by a combination of DNA sequencing and allele-specific amplification techniques with mass spectrometric procedures. The amino acid substitution was found to be Tyr-->Cys, and the corresponding DNA mutation was identified as A-->G at the second position of codon 145 of the beta chain. These variations indicated the presence of Hb Rainier. Haplotype analysis of DNA polymorphisms showed that the beta-globin gene from Hb Rainier was associated with haplotype II. Moreover, structural analyses provided direct identification of an intramolecular disulphide bridge joining the newly inserted beta145Cys with beta93Cys. This is the first report of the occurrence of Hb Rainier in Italy.
Asunto(s)
Hemoglobinas Anormales/genética , Adolescente , Adulto , Sustitución de Aminoácidos , ADN/genética , Femenino , Humanos , Italia , Masculino , Persona de Mediana Edad , Mutación , Linaje , Reacción en Cadena de la PolimerasaRESUMEN
The simultaneous presence of two hemoglobin variants has been detected in a 14-month-old patient affected by thalassemia intermedia. The two variants were characterized by a combination of allele-specific amplification methods and mass spectrometric procedures carried out on isolated globins. These were identified as Hb Lepore-Boston and Hb Neapolis (also known as Hb Dhonburi) or beta 126 (H4)Val-->Gly. Hb Lepore-Boston is the most common hybrid variant detected in Campania and several cases of Hb Neapolis which causes a mild hypochromic microcytic anemia have been identified in this region in the last few years. This is the first report of a double heterozygosity involving Hb Lepore-Boston and Hb Neapolis.
Asunto(s)
Hemoglobinas Anormales/genética , Heterocigoto , Estudios de Seguimiento , Pruebas Hematológicas , Humanos , Lactante , Italia , MasculinoRESUMEN
Waldenström's macroglobulinemia (WM) is an incurable disorder of B cells. Following occasional reports of response to alpha interferon (IFN) and in view of its effectiveness in hairy cell leukemia, we tested this agent in a relatively large group (n = 88) of patients who had an IgM monoclonal component (MC) greater than 10 g/l. Thirty eight patients had a MC > 30 g/l and were classified as Waldenström's macroglobulinemia (WM), while fifty had either WM in an early stage or an IgM monoclonal gammopathy of undeterminated significance (all of them operationally classified as IgM-MGUS). All patients received IFN 3 MU/day for one month and then 3 times/week. Response to treatment was mainly based on MC reduction in two consecutive determinations (> 50%: major response; 25-50%: minor response). Of 36 evaluable WM patients, 12 had a major and 6 a minor response; of 41 evaluable IgM-MGUS patients, 2 had a major and 6 a minor response. In WM patients with a major response, MC reduction was associated with disappearance of hyperviscosity symptoms, raised Hb level and reduced bone marrow lymphoplasmacytosis. At the dose used, tolerance was excellent in the majority of patients; only 15% withdrew from the study due to side effects. Although single cases and very small series have already been reported, no large study collecting quantitative data on the effects of alpha IFN in WM has been published so far. Our results suggest that IFN treatment is not indicated for patients with a low monoclonal component, while it is of clinical benefit in about 50% of patients with IgM > 30 g/l.
Asunto(s)
Inmunoglobulina M/sangre , Interferón-alfa/uso terapéutico , Paraproteinemias/inmunología , Paraproteinemias/terapia , Macroglobulinemia de Waldenström/terapia , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Interferón alfa-2 , Interferón-alfa/efectos adversos , Masculino , Persona de Mediana Edad , Paraproteinemias/sangre , Proteínas Recombinantes , Macroglobulinemia de Waldenström/sangreRESUMEN
Three patients suffering from Waldenström's disease were treated with recombinant human alpha 2b interferon (INTRON-A, Shering-Essex) as single agent (3 megaU every day or three times a week). After four months of treatment, a striking reduction of serum IgM with normalization of the electrophoretic profile was seen in one patient (who had been splenectomized and intensely pretreated with chemotherapy); IgM was about halved in the remaining two patients. With the lower dosage, tolerance was excellent in all cases. Interferon treatment has to be considered in the management of macroglobulinemia.