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1.
Br J Haematol ; 196(3): 706-710, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34816424

RESUMEN

The aim of the present study was to evaluate the significance of low-level minimal/measurable residual disease (MRD) during early consolidation treatment in adult BCR-ABL1-negative acute lymphoblastic leukaemia. The MRD load was monitored by immunoglobulin/T-cell receptor rearrangements and assessed as negative [complete MRD response (CMR)], positive non-quantifiable (MRDnq) and positive quantifiable (MRDq). MRDnq before the first and second consolidation blocks had a comparable negative effect on survival as MRDq. The 5-year overall survival for CMR, MRDnq and MRDq at week 11 was 74·0%, 42·3% and 35·0% respectively. No central nervous system infiltration and MRD at week 11 were independent prognostic factors for survival on multivariate analysis (hazard ratios 0·32 and 2·25).


Asunto(s)
Biomarcadores de Tumor , Proteínas de Fusión bcr-abl/genética , Neoplasia Residual/patología , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Adulto , Factores de Edad , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioterapia de Consolidación , Manejo de la Enfermedad , Femenino , Humanos , Quimioterapia de Inducción , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Pronóstico , Modelos de Riesgos Proporcionales , Resultado del Tratamiento
2.
Acta Oncol ; 60(6): 760-770, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33750258

RESUMEN

INTRODUCTION: BCR-ABL1-like acute lymphoblastic leukemia (ALL) is a high-risk disease with a complex genomic background. Though extensively studied, data on the frequency and mutual associations of present mutations are still incomplete in adult patients. This retrospective study aims to map the genomic landscape of B-other ALL in a cohort of adult patients with a focus on the BCR-ABL1-like ALL subtype. METHODS: We analyzed bone marrow and peripheral blood samples of adult B-other ALL patients treated consecutively at three major Czech teaching hospitals. Samples were analyzed by cytogenetic methods, gene expression profiling, multiplex ligation-dependent probe amplification (MLPA), and next-generation sequencing (NGS). RESULTS: Fifty-eight B-other ALL patients (not BCR-ABL1, KMT2A-rearranged, ETV6-RUNX1, TCF3-PBX1, or iAMP21) were included in the study. Median follow-up was 23.8 months. Samples from 33 patients were available for a gene expression analysis, 48.9% identified as BCR-ABL1-like ALL. Of the BCR-ABL1-like ALL cases, 18.8% harbored IGH-CRLF2 and 12.5% P2RY8-CRLF2 fusion gene. We observed a higher MRD failure rate in BCR-ABL1-like than in non-BCR-ABL1-like ALL patients after the induction treatment (50.0 vs. 13.3%, p=.05). There was a trend to worse progression-free and overall survival in the BCR-ABL1-like group, though not statistically significant. Deletions in IKZF1 gene were found in 31.3% of BCR-ABL1-like cases. Patients with concurrent IKZF1 and CDKN2A/B, PAX5 or PAR1 region deletions (IKZF1plus profile) had significantly worse progression-free survival than those with sole IKZF1 deletion or IKZF1 wild-type (p=.02). NGS analysis was performed in 54 patients and identified 99 short variants in TP53, JAK2, NRAS, PAX5, CREBBP, NF1, FLT3, ATM, KRAS, RUNX1, and other genes. Seventy-five of these gene variants have not yet been described in B-cell precursor ALL to date. CONCLUSION: This study widens existing knowledge of the BCR-ABL1-like and B-other ALL genomic landscape in the adult population, supports previous findings, and identifies a number of novel gene variants.


Asunto(s)
Leucemia-Linfoma Linfoblástico de Células Precursoras , Adulto , Estudios de Cohortes , Perfilación de la Expresión Génica , Genómica , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Estudios Retrospectivos
3.
Vnitr Lek ; 67(E-3): 28-32, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34171949

RESUMEN

Liver cirrhosis is a chronic liver disease in which the liver tissue and the vascular beds are remodeled leading to impaired hepatic function. Portal hypertension and subsequent esophageal varices are a frequent complication of liver cirrhosis and are a cause of mortality in patients with liver cirrhosis. Pregnancy in women with liver cirrhosis is uncommon, the incidence being about 1 in 5 950 pregnancies. Hepatocellular damage and the associated alteration in the metabolism of the sex hormones is thought to be responsible and leads to anovulation. In spite of all these factors, women with cirrhosis can and do become pregnant. Pregnancy is successful in most of the patients with chronic liver disease, but maternal and fetal complication rates are still high for decompensated liver cirrhosis. Portal hypertension associated with pregnancy is a high-risk situation as both pregnancy and portal hypertension share some of the hemodynamic changes. Risks of variceal bleeding and hepatic decompensation increases many fold during pregnancy. Despite the possible complications mentioned above, the maternal-fetal morbidity and mortality rates have been decreased by the current developments in hepatology, prevention of bleeding from varices with drugs and/or endoscopic variceal ligation, improvement in liver transplantation, and an increased experience in these issues. We present a case of a 31-year-old female patient with liver cirrhosis who successfully managed pregnancy and birth without complications after the insertion of transjugular intrahepatic portosystemic shunt (TIPS). Unfortunately, 2 years after delivery, the patient developed lymphoblastic lymphoma and, despite intensive therapy for this disease, the patient died at the age of 40. We did not find any link between liver cirrhosis and lymphoblastic lymphoma.


Asunto(s)
Várices Esofágicas y Gástricas , Hipertensión Portal , Derivación Portosistémica Intrahepática Transyugular , Adulto , Femenino , Hemorragia Gastrointestinal , Humanos , Cirrosis Hepática , Embarazo
4.
Vnitr Lek ; 66(7): 420-424, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33380120

RESUMEN

Cancer immunotherapy has become a standard therapeutic option in oncology over the past few decades. From the early anti-tumor vaccine experiments in the late nineteenth and early twentieth centuries, its journey led through the discovery of the allogeneic hematopoietic stem cell transplantation principles in the nineteen-seventies, introduction of monoclonal antibodies in the nineteen-nineties, their enhancing in the form of immunoconjugates and bispecific antibody constructs, up to todays checkpoint inhibitors and chimeric antigen receptor T-cells (CAR T-cells). Not so long ago, a treatment with genetically modified lymphocytes may have seemed quite like science fiction, but nowadays, these “living drugs“ are already being administered to patients with hematological malignancies in the Czech Republic. Some may see CAR T-cells as a breakthrough treatment method and bright future of oncology, others perhaps just as an overhyped sensation, in which the cost far exceeds the efficacy. Either way, CAR T-cells will soon become a relatively routine treatment option for patients with resistant lymphoproliferative diseases. Our article aims to introduce this new interesting method to specialists outside the fields of hematology and oncology.


Asunto(s)
Neoplasias , Receptores Quiméricos de Antígenos , República Checa , Humanos , Inmunoterapia Adoptiva , Neoplasias/terapia , Receptores de Antígenos de Linfocitos T , Linfocitos T
5.
Vnitr Lek ; 63(5): 348-353, 2017.
Artículo en Checo | MEDLINE | ID: mdl-28726435

RESUMEN

Though acute lymphoblastic leukemia (ALL) is the most common malignancy of childhood age, it is a rare diagnosis in adults. This disease often manifests with common and nonspecific symptoms, so it can easily escape an early diagnostics without a proper blood count examination. We present a case of an adult ALL patient suffering only from severe hips and thighs pain, without any significant blood count abnormities leading to the diagnostics. In the second part of the article, we summarize current highlights regarding this disease.Key words: acute lymphoblastic leukemia - adult - biological treatment - bone pain - CAR T-cells - osteolysis - symptoms.


Asunto(s)
Dolor/etiología , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Adulto , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones
7.
Vnitr Lek ; 61(2): 161-5, 2015 Feb.
Artículo en Checo | MEDLINE | ID: mdl-25813262

RESUMEN

This article describes a case of 68-years-old male with very atypic variation of multiple myeloma occuring as multifocal osteolysis limited to tibiae, cuboid bone, radius and ulna, in the absence of diffuse bone marrow infiltration. The main goal of this article is to point out the importance of permanent awareness during diagnostics and treatment of this insidious disease.


Asunto(s)
Mieloma Múltiple/diagnóstico , Mieloma Múltiple/terapia , Plasmacitoma/diagnóstico , Plasmacitoma/terapia , Anciano , Extremidades , Humanos , Masculino
8.
Clin Case Rep ; 10(3): e05545, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35280086

RESUMEN

Near-haploid acute lymphoblastic leukemia is rare subgroup of the disease, which is very important due to very poor prognosis and resistance to treatment including novel monoclonal antibodies and CAR-T therapy.

9.
Sci Rep ; 11(1): 10124, 2021 05 12.
Artículo en Inglés | MEDLINE | ID: mdl-33980931

RESUMEN

Research objective was to detail COVID-19's natural trajectory in relation to the Czech population's viral load. Our prospective detailed daily questionnaire-based telemonitoring study evaluated COVID-19's impact among 105 outpatients. In accordance with government quarantine requirements, outpatients were divided into a cohort with two negative tests at the end of the disease (40 patients) and a cohort with a new algorithm (65 patients) following a 14-day quarantine. Median follow-up differed significantly between the 2 groups (23 days vs. 16 days). Only 6% of patients were asymptomatic during the entire telemonitoring period. Another 13% of patients were diagnosed asymptomatic, as suspected contacts, yet later developed symptoms, while the remaining 81% were diagnosed as symptomatic on average 6 days following symptom onset. Telemonitoring enabled precise symptom status chronicling. The most frequently reported complaints were fevers, respiratory issues, and anosmia. Six patients were eventually hospitalized for complications detected early after routine telemonitoring. During the extended follow-up (median 181 days), anosmia persisted in 26% of patients. 79% of patients in the new quarantine algorithm cohort reported no symptoms on day 11 compared to just 56% of patients in the two negative test cohort upon first testing negative (median-19 days). The highest viral load occurred within 0-2 days of initial symptom onset. Both the PCR viral load and two consecutive PCR negative sample realizations indicated high interindividual variability with a surprisingly fluctuating pattern among 43% of patients. No definitive COVID-19 symptoms or set of symptoms excepting anosmia (59%) and/or ageusia (47%) were identified. No preexisting medical conditions specifically foreshadowed disease trajectory in a given patient. Without a PCR negativity requirement for quarantine cessation, patients could exhibit fewer symptoms. Our study therefore highlights the urgent need for routine ambulatory patient telemedicine monitoring, early complication detection, intensive mass education connecting disease demeanor with subsequent swift diagnostics, and, notably, the need to reevaluate and modify quarantine regulations for better control of SARS-CoV-2 proliferation.


Asunto(s)
COVID-19/terapia , Adulto , Instituciones de Atención Ambulatoria , COVID-19/diagnóstico , COVID-19/epidemiología , República Checa/epidemiología , Manejo de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pacientes Ambulatorios , Estudios Prospectivos , Cuarentena , SARS-CoV-2/aislamiento & purificación , Telemedicina , Carga Viral
10.
Clin Lymphoma Myeloma Leuk ; 18(11): 743-748, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-30057330

RESUMEN

BACKGROUND: Minimal residual disease (MRD) is an important prognostic maker in acute lymphoblastic leukemia (ALL). However, few data comparing the measurement of adult ALL MRD using different methods in daily practice are available. We conducted an analysis comparing the importance of flow cytometry (FCM) and real-time quantitative polymerase chain reaction (PCR) in the assessment of MRD in adult ALL. PATIENTS AND METHODS: Fifty-six consecutive adult patients with both Philadelphia-negative and -positive ALL treated according to an intensive protocol were enrolled in the study. Bone marrow samples were acquired on day 26 and during week 11 of treatment. MRD evaluation was performed using 8-color FCM and PCR of immunoglobulin or T-cell receptor gene clonal rearrangements and BCR-ABL1, KMT2A-AF4 and E2A-PBX1 fusion genes. RESULTS: On day 26, both FCM and PCR seemed to have good discrimination sensitivity for overall survival (P = .001 to .008) and progression-free survival (P = .03 to .04) prediction for both Philadelphia-positive and -negative cases. The most sensitive method in week 11 was PCR including all results > 0 considered to indicate MRD positivity (P = .002 for overall survival and P = .02 for progression-free survival). PCR with other cutoffs was not sufficiently sensitive in week 11. Moreover, no FCM+ samples were found in week 11. The subanalysis of the Philadelphia-negative patients showed similar results. CONCLUSION: Our analysis showed that both FCM and PCR MRD assessment methods are sensitive for survival prediction during induction. However, we believe FCM could not be sufficiently sensitive in later phases of treatment.


Asunto(s)
Citometría de Flujo/métodos , Neoplasia Residual/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Trasplante de Células Madre/efectos adversos , Adolescente , Adulto , Anciano , Médula Ósea , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Neoplasia Residual/etiología , Neoplasia Residual/metabolismo , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Adulto Joven
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