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3.
Leuk Lymphoma ; 62(1): 194-202, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33021423

RESUMEN

To evaluate long-term real-life results of dasatinib therapy among chronic phase chronic myeloid leukemia patients resistant or intolerant to imatinib, we retrospectively analyzed data of 118 patients treated in centers participating in the database INFINITY. With median follow-up of 37 months, estimated 5-year cumulative incidences of complete cytogenetic and major molecular responses were 78% and 68%, respectively. The estimated 5-year probability of overall survival (OS) and event-free survival (EFS) were 86% and 83%, respectively. Both OS and EFS were significantly improved among patients with BCR-ABL1 transcript level ≤10% at 3 months. Dasatinib toxicity was tolerable however persistent in almost half our patients, even after years of therapy. Pleural effusion occurred in 29% of patients and was responsible for 30% of dasatinib discontinuations. Our results confirmed very good efficacy and acceptable toxicity of dasatinib in second line setting and support the evidence and importance of high-quality real-life CML patient management.


Asunto(s)
Leucemia Mielógena Crónica BCR-ABL Positiva , Leucemia Mieloide de Fase Crónica , Dasatinib/efectos adversos , Humanos , Mesilato de Imatinib/efectos adversos , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Leucemia Mieloide de Fase Crónica/tratamiento farmacológico , Leucemia Mieloide de Fase Crónica/genética , Inhibidores de Proteínas Quinasas/efectos adversos , Estudios Retrospectivos , Resultado del Tratamiento
4.
Leuk Res ; 81: 67-74, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-31051328

RESUMEN

We retrospectively evaluated the role of age and dosage in 372 CML patients (170 women, 202 men) treated with first-line imatinib (IMA) from the records of the CAMELIA registry. The median follow-up of the patients was 82.3 (18.0-177.3) months. The treatment results of 80 elderly patients aged over 65 years at diagnosis were compared in analysis "A" with those of 292 younger patients and in analysis "B" with those of 90 patients younger than 40 and 202 patients aged 40-64. The elderly patients had statistically adverse values of the Sokal, ELTS, and ECOG scores and Charlson comorbidity index in both analyses (p from = 0.012 to ≤ 0.001). Despite a more frequent use of a daily dose lower than 400 mg - in 31 elderly patients (38.8%) than in 45 younger ones (15.4%) (p < 0.001), there were no statistically significant differences in the achievement of optimal haematological, cytogenetic, and molecular responses according to the ELN criteria in both the analyses, A and B. The comparisons of overall survival with CML-related death (OSCML) and event-free survival (EFS) were insignificant inanalysis A (p = 0.07 and 0.396, respectively) but progression-free survival (PFS) differed significantly (p = 0.007). In analysis B OSCML and PFS differed significantly (p = 0.027 and 0.003) but EFS was similar (p = 0.351). Elderly patients with a sustained dose of IMA of 400 mg/day have insignificantly better OS, PFS, and EFS compared to patients treated with a lower dosage of IMA. The results in the treatment of the elderly CML patients were comparable with those of the younger ones in terms of the probabilities of the achievement of optimal ELN responses. However, the results for the survival probabilities were influenced by age and the IMA dosage.


Asunto(s)
Antineoplásicos/uso terapéutico , Mesilato de Imatinib/uso terapéutico , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Sistema de Registros/estadística & datos numéricos , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Relación Dosis-Respuesta a Droga , Femenino , Estudios de Seguimiento , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia
5.
Arch Med Sci ; 14(6): 1416-1423, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-30393497

RESUMEN

INTRODUCTION: Imatinib mesylate is the drug of choice for patients with chronic myeloid leukemia (CML). Imatinib pharmacokinetics is affected by a number of transport proteins and enzymes. MATERIAL AND METHODS: In the present study we evaluated the association of eight polymorphisms in the seven genes CYP3A5*3 (rs776746), CYP3A4*1 (rs2740574), CYP2C9*3 (rs1057910), SLC22A1 (rs683369), ABCB1 (rs1045642, rs1128503), ABCG2 (rs2231142) and ABCC2 (rs717620) with imatinib plasma level and achieving an optimal clinical response in 112 CML patients (53 men and 59 women). RESULTS: No association was found between the examined polymorphisms in rs776746, rs2740574, rs1057910, rs683369, rs1045642, rs1128503, rs2231142, rs717620 and the achieved imatinib plasma level. The influence of rs776746 (CYP3A5*3) on the achievement of a complete cytogenetic response (CCyR) at 6 months was borderline non-significant (p = 0.06). Furthermore, no association was demonstrated between rs776746 polymorphisms and the achievement of a major molecular response (MMR) at 12 or 18 months. Polymorphisms rs776746, rs2740574, rs1057910, rs683369, rs1045642, rs1128503, rs2231142, rs717620 showed no impact on the optimal therapeutic response. CONCLUSIONS: Despite the results of some other studies, no other polymorphism we analyzed was associated with imatinib plasma level or clinical response. The treatment outcomes cannot be predicted using the candidate gene approach and treatment decisions cannot be made according to the polymorphisms investigated in this study.

7.
Haematologica ; 102(8): 1361-1367, 2017 08.
Artículo en Inglés | MEDLINE | ID: mdl-28522574

RESUMEN

Monitoring of single cell signal transduction in leukemic cellular subsets has been proposed to provide deeper understanding of disease biology and prognosis, but has so far not been tested in a clinical trial of targeted therapy. We developed a complete mass cytometry analysis pipeline for characterization of intracellular signal transduction patterns in the major leukocyte subsets of chronic phase chronic myeloid leukemia. Changes in phosphorylated Bcr-Abl1 and the signaling pathways involved were readily identifiable in peripheral blood single cells already within three hours of the patient receiving oral nilotinib. The signal transduction profiles of healthy donors were clearly distinct from those of the patients at diagnosis. Furthermore, using principal component analysis, we could show that phosphorylated transcription factors STAT3 (Y705) and CREB (S133) within seven days reflected BCR-ABL1IS at three and six months. Analyses of peripheral blood cells longitudinally collected from patients in the ENEST1st clinical trial showed that single cell mass cytometry appears to be highly suitable for future investigations addressing tyrosine kinase inhibitor dosing and effect. (clinicaltrials.gov identifier: 01061177).


Asunto(s)
Leucemia Mieloide de Fase Crónica/tratamiento farmacológico , Pirimidinas/uso terapéutico , Transducción de Señal/efectos de los fármacos , Análisis de la Célula Individual/métodos , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Proteínas de Fusión bcr-abl/metabolismo , Humanos , Leucemia Mieloide de Fase Crónica/patología , Leucocitos/metabolismo , Fosforilación , Proteínas Tirosina Quinasas/uso terapéutico , Pirimidinas/farmacología , Factor de Transcripción STAT3/metabolismo , Transducción de Señal/inmunología
8.
Acta Medica (Hradec Kralove) ; 59(2): 50-3, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27526305

RESUMEN

BACKGROUND: A combination of low-dose thalidomide and corticosteroids is a treatment option for anaemic patients with primary myelofibrosis (PMF) who are not eligible for allogeneic hematopoietic stem cell transplantation. METHODS: We describe the outcomes of 13 patients with PMF treated with thalidomide 50 mg daily in combination with prednisone 0.5 mg/kg daily. Treatment responses were seen in 10/13 (77%) patients with a median onset of therapeutic effect at 4 weeks (range 3-7 weeks) after treatment initiation. Improvements of anaemia and thrombocytopenia and reduction in splenomegaly were observed in 70%, 38%, and 30% of patients, respectively. Four of six initially transfusion-dependent patients became transfusion independent following the therapy. The median duration of treatment response was 18 months (range 3-35 months). The treatment was well tolerated, with only one patient discontinuing therapy due to toxicity. Responders included both patients with and without JAK2 V617F, and included patients with both newly diagnosed and longstanding PMF. CONCLUSIONS: Our retrospective analysis confirmed that the therapy with low-doses thalidomide with prednisone in patients with PMF achieves significant response rate in anaemia with low treatment toxicity.


Asunto(s)
Anemia Aplásica/tratamiento farmacológico , Prednisona/administración & dosificación , Mielofibrosis Primaria/tratamiento farmacológico , Talidomida/administración & dosificación , Anciano , Anciano de 80 o más Años , Anemia Aplásica/sangre , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recuento de Plaquetas , Mielofibrosis Primaria/sangre
9.
Vnitr Lek ; 61(9): 785-6, 788-91, 2015 Sep.
Artículo en Checo | MEDLINE | ID: mdl-26465277

RESUMEN

INTRODUCTION: Treatment of chronic myeloid leukemia (CML) with tyrosine kinase inhibitors (TKI) has significantly changed the survival of patients of all age categories. In our work, we have tried retrospectively to analyze a therapeutic response and toxicity of imatinib according to age of patients ( 60 years vs > 60 years). Patients have started treatment with imatinib in 2001-2013 in our department. The duration of treatment was at least 18 months. PATIENTS AND METHODS: The whole group contains 103 patients (52 women, 51 men) with a median age at diagnosis of CML 55 years (range 19-88 years). The first group includes 68 the younger patients (31 women, 37 men) with a median age at diagnosis 43 years (range 19-59 years) and the second group 35 the elderly patients (21 women, 14 men) with a median age at diagnosis 70 years (range 61-86 years). Median imatinib dose in both groups was the same - 400 mg per day (range 200-600 mg). RESULTS: In the elderly patients we observed higher rates of hematological toxicities (p = 0.0059). After 12 months treatment, a complete cytogenetic response (CCyR) was achieved in 90 % of younger patients and in 74 % of the elderly patients, respectively. Major molecular response (MMR) at 18 months treatment was achieved in 79 % of the younger group and in 63 % of the elderly group. CONCLUSION: The results represent in both groups very good therapeutic response independent of age of patients at the time of CML diagnosis.


Asunto(s)
Mesilato de Imatinib/uso terapéutico , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Mesilato de Imatinib/efectos adversos , Leucemia Mielógena Crónica BCR-ABL Positiva/diagnóstico , Masculino , Persona de Mediana Edad , Inducción de Remisión , Estudios Retrospectivos , Resultado del Tratamiento , Adulto Joven
10.
Haematologica ; 99(8): 1395-402, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24997149

RESUMEN

Long-term granulocyte-colony stimulating factor treatment has been shown to be safe and effective in severe chronic neutropenia patients. However, data on its use during pregnancy are limited. To address this issue, we analyzed all pregnancies reported to the European branch of the Severe Chronic Neutropenia International Registry since 1994. A total of 38 pregnancies in 21 women with chronic neutropenia (16 pregnancies in 10 women with congenital, 10 in 6 women with cyclic, 12 in 5 women with idiopathic neutropenia) were reported. Granulocyte-colony stimulating factor was administered throughout pregnancy in 16 women and for at least one trimester in a further 5 women. No major differences were seen between treated and untreated women with respect to pregnancy outcome, newborn complications and infections. In addition, we evaluated the genetic transmission of known or suspected genetic defects in 16 mothers having 22 newborns as well as in 8 men fathering 15 children. As a proof of inheritance, neutropenia was passed on to the newborn in 58% from female and in 62% from male patients with ELANE mutations, but also to some newborns from parents with unknown gene mutation. Based on our results, granulocyte-colony stimulating factor therapy has been shown to be safe for mothers throughout pregnancies and for newborns without any signs of teratogenicity. With an increasing number of adult patients, genetic counseling prior to conception and supportive care of mothers during pregnancy are crucial. The acceptance of having affected children may reflect the high quality of life obtained due to this treatment.


Asunto(s)
Neutropenia/diagnóstico , Neutropenia/terapia , Complicaciones Hematológicas del Embarazo/diagnóstico , Complicaciones Hematológicas del Embarazo/terapia , Sistema de Registros , Adulto , Estudios de Cohortes , Manejo de la Enfermedad , Europa (Continente)/epidemiología , Femenino , Humanos , Recién Nacido , Masculino , Neutropenia/epidemiología , Embarazo , Complicaciones Hematológicas del Embarazo/epidemiología , Resultado del Embarazo/epidemiología , Resultado del Tratamiento , Adulto Joven
11.
Hematol Oncol ; 32(2): 87-93, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23963760

RESUMEN

This multicentre study focused on monitoring imatinib mesylate (IMA) trough plasma (Ctrough ) and intracellular (IMA Cintrac ) concentrations in 228 chronic myelogenous leukaemia patients. The median of measured IMA Ctrough in our patient group was 905.8 ng ml (range: 27.7-4628.1 ng/ml). We found a correlation between IMA Ctrough and alpha 1-acid glycoprotein plasma concentrations (rS = 0.42; p < 0.001). All other analysed parameters revealed only weak (gender, dose of IMA per kg) or not significant (age, albumin, creatinine plasma concentration or body mass index) impact on measured IMA Ctrough. The IMA Ctrough decreased during the first 6 months and significantly increased later during treatment. The IMA Ctrough at the first month of therapy did not differ between patients with and without an optimal response at the 12th (p = 0.724) and 18th month (p = 0.135) of therapy. There were no significant differences in medians of IMA Ctrough between both groups measured during the first year of treatment. The IMA Cintrac during the first month were not different between patients with and without an optimal response at the 6th (p = 0.273) and the 12th month (p = 0.193) of therapy. Our data obtained from real life clinical practice did not find a benefit of routine and regular IMA Ctrough nor IMA Cintrac therapeutic drug monitoring in chronic myelogenous leukaemia patients or for subsequent adjustments of the IMA dose based on these results. Moreover, actual alpha 1-acid glycoprotein plasma concentration should be used for proper interpretation of IMA Ctrough results.


Asunto(s)
Antineoplásicos/sangre , Antineoplásicos/uso terapéutico , Benzamidas/sangre , Benzamidas/uso terapéutico , Leucemia Mielógena Crónica BCR-ABL Positiva/sangre , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Piperazinas/sangre , Piperazinas/uso terapéutico , Pirimidinas/sangre , Pirimidinas/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/farmacocinética , Benzamidas/farmacocinética , Femenino , Humanos , Mesilato de Imatinib , Leucemia Mielógena Crónica BCR-ABL Positiva/metabolismo , Masculino , Persona de Mediana Edad , Piperazinas/farmacocinética , Pirimidinas/farmacocinética , Resultado del Tratamiento , Adulto Joven
12.
Am J Hematol ; 88(9): 790-7, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23760739

RESUMEN

Using the data of 723 chronic myeloid leukemia (CML) patients in the chronic phase, we analyzed the prognostic value of the Sokal, Euro, and EUTOS scores as well as the level of BCR-ABL1 and the achievement of complete cytogenetic response (CCgR) at 3 months of imatinib therapy in relation to the so-called current survival measures: the current cumulative incidence (CCI) reflecting the probability of being alive and in CCgR after starting imatinib therapy; the current leukemia-free survival (CLFS) reflecting the probability of being alive and in CCgR after achieving the first CCgR; and the overall survival. The greatest difference between the CCI curves at 5 years after initiating imatinib therapy was observed for the BCR-ABL1 transcripts at 3 months. The 5-year CCI was 94.3% in patients with BCR-ABL1 transcripts ≤ 10% and 57.1% in patients with BCR-ABL1 transcripts > 10% (P = 0.005). Therefore, the examination of BCR-ABL1 transcripts at 3 months may help in early identification of patients who are likely to perform poorly with imatinib. On the other hand, CLFS was not significantly affected by the considered stratifications. In conclusion, our results indicate that once the CCgR is achieved, the prognosis is good irrespective of the starting prognostic risks.


Asunto(s)
Antineoplásicos/uso terapéutico , Benzamidas/uso terapéutico , Proteínas de Fusión bcr-abl/genética , Leucemia Mieloide de Fase Crónica/genética , Piperazinas/uso terapéutico , Pirimidinas/uso terapéutico , ARN Mensajero/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Proteínas de Fusión bcr-abl/metabolismo , Humanos , Mesilato de Imatinib , Leucemia Mieloide de Fase Crónica/diagnóstico , Leucemia Mieloide de Fase Crónica/tratamiento farmacológico , Leucemia Mieloide de Fase Crónica/mortalidad , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , ARN Mensajero/metabolismo , Inducción de Remisión , Proyectos de Investigación , Análisis de Supervivencia , Resultado del Tratamiento
13.
Cancer Med ; 2(2): 216-25, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23634289

RESUMEN

We evaluated responses to the treatment and long-term outcomes of chronic myeloid leukemia patients treated with imatinib as first-line treatment in routine clinical setting from two countries with centralized tyrosine kinase inhibitors (TKIs) treatment. We assessed prognostic significance of European LeukemiaNet (ELN) 2006- and 2009-defined responses and the prognostic value of molecular responses at defined time points on 5-year survivals. Among the cumulative rates of incidence of hematologic, cytogenetic, and molecular responses and all important survival parameters, we evaluated the prognostic significance of different BCR-ABL transcript-level ratios (≤1%; >1%-≤10%; >10%) at 3, 6, 12, and 18 months (n = 199). The ELN optimal response criteria and their predictive role were significantly beneficial for event-free survival at all given time points. We found significant improvement in survivals of patients with BCR-ABL lower than 10% in the 6th and 12th months. Significantly better outcome was found in patients who achieved major molecular response (MMR) in the 12th month. The cumulative incidences of complete cytogenetic response (CCyR) and MMR were significantly associated with the molecular response in the 3rd month. The ELN response criteria and their predictive role were helpful at given time points; however, the 2009 definition did not significantly alter the prognostic accuracy compared with that of the 2006 definition. The significant value was observed for cytogenetic responses at the 6th and 12th month. Moreover, progression-free and event-free survivals were improved with MMR at the 12th month.


Asunto(s)
Antineoplásicos/uso terapéutico , Benzamidas/uso terapéutico , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Piperazinas/uso terapéutico , Inhibidores de Proteínas Quinasas/uso terapéutico , Pirimidinas/uso terapéutico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Proteínas de Fusión bcr-abl/genética , Humanos , Mesilato de Imatinib , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Persona de Mediana Edad , Pronóstico , Tasa de Supervivencia , Resultado del Tratamiento , Adulto Joven
14.
PLoS One ; 6(8): e23022, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21857985

RESUMEN

Before the era of tyrosine kinase inhibitors (TKIs), interferon-alpha (IFN-α) was the treatment of choice in chronic myeloid leukemia (CML). Curiously, some IFN-α treated patients were able to discontinue therapy without disease progression. The aim of this project was to study the immunomodulatory effects of IFN-α in CML patients in prolonged remission and isolate biological markers predicting response. Due to rarity of patients on IFN-α monotherapy, a relatively small cohort of patients still on treatment (IFN-ON, n = 10, median therapy duration 11.8 years) or had discontinued IFN-α therapy but remained in remission for >2 years (IFN-OFF, n = 9) were studied. The lymphocyte immunophenotype was analyzed with a comprehensive flow cytometry panel and plasma cytokine levels were measured with multiplex bead-based assay. In addition, the clonality status of different lymphocyte subpopulations was analyzed by TCR γ/δ rearrangement assay. Median NK-cell absolute number and proportion from lymphocytes in blood was higher in IFN-OFF patients as compared to IFN-ON patients or controls (0.42, 0.19, 0.21×10(9)/L; 26%, 12%, 11%, respectively, p<0.001). The proportion of CD8+ T-cells was significantly increased in both patient groups and a larger proportion of T-cells expressed CD45RO. Most (95%) patients had significant numbers of oligoclonal lymphocytes characterized by T-cell receptor γ/δ rearrangements. Strikingly, in the majority of patients (79%) a distinct clonal Vγ9 gene rearrangement was observed residing in γδ(+) T-cell population. Similar unique clonality pattern was not observed in TKI treated CML patients. Plasma eotaxin and MCP-1 cytokines were significantly increased in IFN-OFF patients. Despite the limited number of patients, our data indicates that IFN-α treated CML patients in remission have increased numbers of NK-cells and clonal γδ(+) T-cells and a unique plasma cytokine profile. These factors may relate to anti-leukemic effects of IFN-α in this specific group of patients and account for prolonged therapy responses even after drug discontinuation.


Asunto(s)
Citocinas/metabolismo , Interferón-alfa/uso terapéutico , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Linfocitos/efectos de los fármacos , Receptores de Antígenos de Linfocitos T gamma-delta/metabolismo , Adulto , Secuencia de Aminoácidos , Secuencia de Bases , Complejo CD3/metabolismo , Femenino , Citometría de Flujo , Reordenamiento Génico de Linfocito T/genética , Humanos , Factores Inmunológicos/uso terapéutico , Inmunofenotipificación , Leucemia Mielógena Crónica BCR-ABL Positiva/inmunología , Leucemia Mielógena Crónica BCR-ABL Positiva/metabolismo , Antígenos Comunes de Leucocito/metabolismo , Linfocitos/inmunología , Linfocitos/metabolismo , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Reacción en Cadena en Tiempo Real de la Polimerasa , Receptores de Antígenos de Linfocitos T gamma-delta/genética , Inducción de Remisión , Factores de Tiempo , Adulto Joven
15.
Eur J Haematol ; 87(2): 157-68, 2011 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-21535160

RESUMEN

BACKGROUND: Most results on the treatment of chronic myeloid leukaemia (CML) with imatinib were obtained from clinical trials that may differ from the routine practice. We report the results of treatment of consecutive patients with CML at ten major centres during 2000-2008. PATIENTS AND METHODS: Data reporting was retrospective in 2000-2004 and prospective from 2005 on. A total of 661 patients [301 women and 360 men; median age 51 (range, 15-83)] with Ph+CML were registered. The median follow-up was 46.1 months (0-122.2). RESULTS: Most patients were treated with first- (379; 57.3%) or second-line (193; 29.2%) imatinib; some of the patients underwent allogeneic hematopoietic stem cell transplantation (AHSCT) (83; 12.6%), but 6.1% were treated with other modalities [40 patients; median age 66 (range, 32-83)]. The probability of overall survival (OS) at 5 years, according to Kaplan and Meier, was 88.9%, 77.5% and 68.7% for chronic-phase patients treated with first-line imatinib, second-line imatinib and first-line AHSCT, respectively, but only 25.2% for patients receiving other modalities. The OS was dependent on the disease phase and Sokal, Hasford and European group for blood and marrow transplantation (EBMT) risk scores (P<0.001; each). Only 46.2% of deaths in patients treated with other modalities were attributable to CML. Elderly patients over 65 years achieved similar response rates and progression-free survival to the younger ones. There was a trend for inferior results of AHSCT performed after the failure of imatinib (P=0.075), probably as a result of differences in EBMT risk scores (P<0.001). CONCLUSIONS: The ability to achieve results comparable to those of previous clinical studies in our CML cohort was influenced by centralised care. Decisions not to initiate imatinib or to delay AHSCT may have a negative impact on OS, but comorbidities may limit the treatment potential of imatinib in the elderly.


Asunto(s)
Leucemia Mielógena Crónica BCR-ABL Positiva/terapia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Benzamidas , República Checa/epidemiología , Supervivencia sin Enfermedad , Femenino , Trasplante de Células Madre Hematopoyéticas , Humanos , Mesilato de Imatinib , Estimación de Kaplan-Meier , Leucemia Mielógena Crónica BCR-ABL Positiva/mortalidad , Masculino , Persona de Mediana Edad , Piperazinas/uso terapéutico , Estudios Prospectivos , Pirimidinas/uso terapéutico , Sistema de Registros , Estudios Retrospectivos , Eslovaquia/epidemiología , Trasplante Homólogo , Adulto Joven
17.
Cancer Genet Cytogenet ; 191(1): 1-9, 2009 May.
Artículo en Inglés | MEDLINE | ID: mdl-19389502

RESUMEN

Reported here are 72 previously treated Philadelphia chromosome-positive (Ph+) CML patients on imatinib (IM) therapy, with a focus on patients with additional chromosomal aberrations (CAs). At the start of IM treatment, 49 patients exhibited only the Ph chromosome (68%) and 23 patients (32%) had one or more additional CAs. The most frequent additional changes were deletions on the der(9q) (8 of 23), trisomy 8 (3 of 23), and an extra copy of the Ph chromosome (2 of 23). Five patients had a complex karyotype. At the latest follow-up, 49 of the 72 patients (68%) were alive, including 15 of the 23 patients with additional CAs (65%). Median follow-up was 6.6 years; median duration of IM treatment was 4.4 years. In all, 35 of the 49 patients with Ph only (71%) and 10 of the 23 patients with additional CAs (43%) achieved complete cytogenetic response. All patients with deletion on der(9q) achieved complete cytogenetic response. There was no statistically significant difference in the overall survival of patients with additional CAs and patients with Ph as the sole abnormality. Patients in accelerated phase had significantly worse overall survival on IM, regardless of additional CAs. The present results confirm that the majority of previously treated Ph+ CML patients benefit from starting IM therapy, including patients with defined additional changes. In contrast, patients with complex karyotypes have poor prognosis, even with IM.


Asunto(s)
Aberraciones Cromosómicas , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Piperazinas/uso terapéutico , Pirimidinas/uso terapéutico , Adolescente , Adulto , Anciano , Benzamidas , Estudios de Cohortes , Resistencia a Antineoplásicos , Femenino , Estudios de Seguimiento , Humanos , Mesilato de Imatinib , Hibridación Fluorescente in Situ , Cariotipificación , Leucemia Mielógena Crónica BCR-ABL Positiva/diagnóstico , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Masculino , Persona de Mediana Edad , Análisis de Supervivencia , Resultado del Tratamiento
18.
Acta Medica (Hradec Kralove) ; 47(3): 181-5, 2004.
Artículo en Inglés | MEDLINE | ID: mdl-15568736

RESUMEN

The apoptosis failure in cytostatic treatment of haemoblastosis is one of the means of chemoresistance. We were interested in the relationship of the after-doxorubicin-treatment-AML cells apoptosis and the immunophenotype, selected clinical and laboratory parameters, and also the P-gp, MRP, LRP, Bcl-2, Bax proteins expression. All analysis were evaluated with the flow cytometry method. To detect apoptotic cells in the sample, we used three methods: annexin test, TUNEL (TdT-mediated dUTP nick end labeling) test, and caspase 8 detection. After the cell cultivation the statisticaly important increase of apoptotic cells in the culture was apparent. The relation between the AML blast in vitro reaction and some clinical parameters such as the age of patient, white blood cell count, and blast percentage was also observed.


Asunto(s)
Antibióticos Antineoplásicos/uso terapéutico , Apoptosis/efectos de los fármacos , Doxorrubicina/uso terapéutico , Leucemia Mieloide/tratamiento farmacológico , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/análisis , Antígenos CD34/análisis , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Humanos , Técnicas In Vitro , Leucemia Mieloide/metabolismo , Leucemia Mieloide/patología , Masculino , Persona de Mediana Edad , Proteínas Proto-Oncogénicas c-bcl-2/análisis
19.
Leuk Res ; 28(4): 415-9, 2004 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-15109543

RESUMEN

Kinetics of BCR-ABL transcript levels were determined in 19 patients with chronic myeloid leukemia (CML) treated with imatinib for chronic (CP) or accelerated phase (AP). Patients could be divided into three groups with: (1) a sharp and sustained decrease in BCR-ABL transcript level reaching 0.1-0.002% (only CP); (2) an early BCR-ABL overexpression up to 2500% (only AP); and (3) a stable trend with BCR-ABL values between 10 and 100% (CP, AP). In group 1, relapses were not developed within the follow-up; in group 2, patients progressed to blast crisis; in group 3, BCR-ABL overexpression appeared after 12 months in some patients and disease relapses were found 2-16 weeks later. It is summarized that BCR-ABL transcript kinetics clearly characterize responses to imatinib treatment and are highly predictive for disease progression.


Asunto(s)
Antineoplásicos/uso terapéutico , Proteínas de Fusión bcr-abl/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Piperazinas/uso terapéutico , Pirimidinas/uso terapéutico , Transcripción Genética/efectos de los fármacos , Adulto , Anciano , Benzamidas , Crisis Blástica/genética , Femenino , Proteínas de Fusión bcr-abl/efectos de los fármacos , Humanos , Mesilato de Imatinib , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
20.
Acta Medica (Hradec Kralove) ; 46(3): 85-9, 2003.
Artículo en Inglés | MEDLINE | ID: mdl-14677715

RESUMEN

The publication provides an up-to-date review of the significance of cytogenetic abnormalities in chronic myelogenous leukemia (CML) and the development of a promising agent with specific molecular target against tyrosine kinase, product of the BCR-ABL fusion gene, namely imatinib mesylate (STI 571, Glivec). The publication summarizes the achieved results with this compound in the chronic phase CML (in patients resistant to interferon and in newly diagnosed patients) further in patients in the accelerated phase and in blast crisis and in patients in relapse after allogeneic stem cells transplantations for CML. The results in Ph+ acute lymphoblastic leukemia are also presented. The mechanisms of resistance to imatinib mesylate and the possibilities how to overcome or circumvent it are mentioned (escalation of the dosage, combination of imatinib with some other treatment modalities as immunotherapy, interferon or convention chemotherapy and development of new drugs).


Asunto(s)
Antineoplásicos/administración & dosificación , Inhibidores Enzimáticos/administración & dosificación , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Piperazinas/administración & dosificación , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Pirimidinas/administración & dosificación , Administración Oral , Benzamidas , Humanos , Mesilato de Imatinib
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