RESUMEN
Patients with Philadelphia chromosome-positive (Ph+) and/or BCR-ABL+ acute lymphoblastic leukemia (ALL) have extremely poor prognoses. Most of these patients have additional, heterogenous karyotype abnormalities, the majority of which have uncertain clinical significance. In this study we analyzed the clinical characteristics, karyotype abnormalities, and outcome of 77 patients with Ph+ and/or BCR-ABL+ ALL registered in Poland in 1997-2004. In 31/55 patients with known karyotype, the sole t(9;22)(q34;q11) abnormality had been diagnosed; in one patient, variant translocation t(4;9;22)(q21q31.1;q34;q11), and additional abnormalities in 23 (42%) patients, had been diagnosed. The characteristics of the patients with Ph chromosome and additional abnormalities were not significantly different when compared with the entire analyzed group. Out of 77 patients, 54 (70%) achieved first complete remission (CR1) after one or more induction cycles. The overall survival (OS) probability of 2 years was 63, 43, and 17% for patients treated with allogeneic stem cell transplantation (alloSCT), autologous SCT, and chemotherapy, respectively (log rank p=0.002). Median OS from the time of alloSCT was significantly longer for patients transplanted in CR1 compared with alloSCT in CR >1 (p=0.032). There were no significant differences in CR rate, disease-free survival (DFS), and OS for patients with t(9;22) and additional abnormalities compared with the whole group. Only WBC >20 G/l at diagnosis adversely influenced OS probability (log rank p=0.0017). In conclusion, our data confirm poor outcome of Ph+ and/or BCR-ABL+ ALL. Only patients who received alloSCT in CR1 had longer DFS and OS. We have shown that additional karyotype abnormalities did not influence the clinical characteristics of the patients; however, their influence on treatment results needs to be further assessed.
Asunto(s)
Proteínas de Fusión bcr-abl/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/terapia , Cromosoma Filadelfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Citarabina/administración & dosificación , Supervivencia sin Enfermedad , Femenino , Trasplante de Células Madre Hematopoyéticas , Humanos , Cariotipificación , Leucemia Mielógena Crónica BCR-ABL Positiva/diagnóstico , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Masculino , Mercaptopurina/administración & dosificación , Metotrexato/administración & dosificación , Persona de Mediana Edad , Polonia , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Inducción de Remisión , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
In diagnosis of CMV infection various laboratory methods are used. The methods based on detection of viral nucleic acids have been introduced routinely in many laboratories. The aim of this study was to compare nucleic acid hybridisation method and various variants of PCR methods with respect to their ability to detect CMV DNA. The studied material comprised 60 blood samples from 19 patients including 13 renal transplant recipients and 6 with acute leukaemia. The samples were subjected to hybridisation (Murex Hybrid Capture System CMV DNA) and PCR carried out in 3 variants: with one pair of primers (single PCR), nested PCR and Digene SHARP System with detection of PCR product using a genetic probe in ELISA system. The sensitivity of the variants ranged from 10(0) particles of viral DNA in nested PCR to 10(2) in single PCR. The producer claimed the sensitivity of the hybridisation test to be 3 x 10(5) and it seems to be sufficient for detection of CMV infection. The obtained results show that sensitivity of hybridisation was comparable to that of single PCR and the possibility of obtaining quantitative results makes it superior, on efficacy of antiviral therapy, especially in monitoring CMV infection in immunossuppressed patients and in following the efficacy of antiviral treatment.
Asunto(s)
Infecciones por Citomegalovirus/diagnóstico , Huésped Inmunocomprometido/inmunología , Terapia de Inmunosupresión/efectos adversos , Hibridación de Ácido Nucleico/métodos , Reacción en Cadena de la Polimerasa/métodos , Infecciones por Citomegalovirus/inmunología , ADN Viral/análisis , Humanos , Trasplante de Riñón/inmunología , Leucemia/inmunologíaRESUMEN
The purpose of this paper was to estimate the best method of CMV diagnosis in leukemic patients. Materials from 9 patients (serum, heparinized blood and urine) were investigated by serological methods (ELISA and Western blot), for the presence of specific antigens and virus capable of replication, and also by genetic methods (hybridization and PCR). It seems, that the best method for CMV diagnosis in leukemic patients is hybridization performed in quantitation variant, and that DNA CMV level of approximately 20 pg/ml of blood was not linked to symptomatic infection.
Asunto(s)
Infecciones por Citomegalovirus/diagnóstico , Leucemia/complicaciones , Adolescente , Adulto , Anticuerpos Antivirales/análisis , Western Blotting , Citomegalovirus/aislamiento & purificación , Infecciones por Citomegalovirus/etiología , ADN Viral/análisis , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Hibridación de Ácido Nucleico , Reacción en Cadena de la Polimerasa , Pruebas SerológicasRESUMEN
Mitoxantrone is a new anthracenodione derivative with a high antineoplastic activity in proliferative diseases of the haemopoietic system. In the Institute of Haematology in Warsaw and in the Department of Haematology, Silesian Medical Academy in Katowice this agent was used in combination with cytarabine in 49 cases of acute leukaemia (35 with acute myeloid leukaemia and 14 with acute lymphoblastic leukaemia). The preparations used were Mitoxantrone (POLFA Works in Jelenia Góra) and Novantrone (Lederle). These agents were given intravenously in doses of 10-20 mg/m2 for 3 days in combination with cytarabine in three doses: 100 mg/m2 on days 1 through 7, and 1 g/m2 or 3 g/m2 every 12 hours on days 1 through 4 of the treatment. Complete remission was obtained in 17 cases (35%), including 13 with acute myeloid leukaemia (37%) and 4 with acute lymphoblastic leukaemia (29). The most frequent side effects were: long-lasting pancytopenia (in 100% of cases), hair loss (39%) and gastrointestinal toxicity (33%). No significant differences were noted in the effectiveness and toxicity between these two preparations. In the light of the presented results it may be accepted that the combination of mitoxantrone with cytarabine is an important advance in the treatment of acute leukaemias.