Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 45
Filtrar
1.
Cancers (Basel) ; 16(7)2024 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-38611011

RESUMEN

Azacitidine (AZA) is recognized as a vital drug used in the therapy of myelodysplastic syndromes (MDS) due to its beneficial effect on survival and quality of life. Nevertheless, many patients fail to respond to AZA treatment, as prognostic factors still are not identified. The present retrospective analysis included 79 patients with MDS treated with AZA as first-line therapy in a real-life setting. The percentage of patients with good, intermediate, and poor cytogenetics was 46.8%, 11.4%, and 34.2%, respectively. The overall response rate (complete remission [CR], partial remission [PR], and hematological improvement [HI]) was 24%. The CR, PR, and HI rates were 13.9%, 2.5%, and 7.6%, respectively. Stable disease (SD) was documented in 40.5% of patients. The median overall survival (OS) and progression-free survival (PFS) were 17.6 and 14.96 months, respectively. Patients with ORR and SD had a significantly longer median OS (23.8 vs. 5.7 months, p = 0.0005) and PFS (19.8 vs. 3.5 months, p < 0.001) compared to patients who did not respond to AZA. In univariate analysis, only an unfavorable cytogenetic group was a prognostic factor of a lower response rate (p = 0.03). In a multivariate model, older age (p = 0.047), higher IPSS (International Prognostic Scoring System) risk (p = 0.014), and higher IPSS-R cytogenetic risk (p = 0.004) were independent factors of shorter OS. Independent prognostic factors for shorter PFS were age (p = 0.001), IPSS risk (p = 0.02), IPSS cytogenetic risk (p = 0.002), and serum ferritin level (p = 0.008). The safety profile of AZA was predictable and consistent with previous studies. In conclusion, our study confirms the efficacy and safety of AZA in a real-world population and identifies potential biomarkers for response and survival.

2.
Ann Hematol ; 2024 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-38438627

RESUMEN

Interferon-based therapies, such as ropeginterferon alfa-2b have emerged as promising disease-modifying agents for myeloproliferative neoplasms (MPNs), including essential thrombocythemia (ET). Current ET treatments aim to normalize hematological parameters and reduce the thrombotic risk, but they do not modify the natural history of the disease and hence, have no impact on disease progression. Ropeginterferon alfa-2b (trade name BESREMi®), a novel, monopegylated interferon alfa-2b with an extended administration interval, has demonstrated a robust and sustained efficacy in polycythemia vera (PV) patients. Given the similarities in disease pathophysiology and treatment goals, ropeginterferon alfa-2b holds promise as a treatment option for ET. The ROP-ET trial is a prospective, multicenter, single-arm phase III study that includes patients with ET who are intolerant or resistant to, and/or are ineligible for current therapies, such as hydroxyurea (HU), anagrelide (ANA), busulfan (BUS) and pipobroman, leaving these patients with limited treatment options. The primary endpoint is a composite response of hematologic parameters and disease-related symptoms, according to modified European LeukemiaNet (ELN) criteria. Secondary endpoints include improvements in symptoms and quality of life, molecular response and the safety profile of ropeginterferon alfa-2b. Over a 3-year period the trial assesses longer term outcomes, particularly the effects on allele burden and clinical outcomes, such as disease-related symptoms, vascular events and disease progression. No prospective clinical trial data exist for ropeginterferon alfa-2b in the planned ET study population and this study will provide new findings that may contribute to advancing the treatment landscape for ET patients with limited alternatives. TRIAL REGISTRATION: EU Clinical Trials Register; EudraCT, 2023-505160-12-00; Registered on October 30, 2023.

3.
Contemp Oncol (Pozn) ; 27(2): 113-117, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37794994

RESUMEN

Primary pulmonary Hodgkin's lymphoma (PPHL) is a rare subtype of lymphoma that comprises a small percentage of primary pulmonary lymphomas. Due to its rarity and nonspecific symptoms, PPHL often presents diagnostic challenges. This case report presents a unique case of PPHL mimicking granulomatosis with polyangiitis, emphasizing the difficulties encountered during the diagnostic process. A 53-year-old female presented with vague symptoms including weakness, oedema, dry cough, and nasal cavity ulceration. Laboratory investigations revealed elevated C-reactive protein levels, a white blood cell count with neutrophilia, and lymphopaenia. Initial treatment with oral corticosteroids for suspected polyangiitis yielded no response. The patient subsequently developed a low-grade fever and pruritic erythematous rash. Diagnostic procedures, including bronchial brush biopsy, bronchial washing, mediastinal lymph node biopsy, nasal cavity ulceration biopsy, and initial lung biopsy, were inconclusive and resulted in exclusion of granulomatosis with polyangiitis. A subsequent computed tomography scan indicated disease progression in the left lung. A lung biopsy revealed fibrotic tissue with nodules containing Hodgkin- Reed-Sternberg cells, leading to the final diagnosis of classic Hodgkin lymphoma, nodular sclerosis subtype. Positron emission tomography scan findings confirmed PPHL. The patient received multiple chemotherapeutic regimens, with brentuximab vedotin demonstrating efficacy as the sole effective treatment. This exceptional case of PPHL underscores the extensive diagnostic and therapeutic workup involving a multidisciplinary team of clinicians, radiologists, and pathologists. Increased awareness of PPHL and its distinctive features will aid in the diagnosis of similar cases in the future, benefitting both clinicians and pathologists.

4.
Expert Opin Investig Drugs ; 32(1): 53-67, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36669827

RESUMEN

INTRODUCTION: Acute myeloid leukemia (AML) is a heterogeneous disease characterized by many cytogenetic and molecular alterations. Due to better knowledge of the molecular basis of AML, many targeted therapies have been introduced and registered, e.g. FMS-like tyrosine kinase 3 inhibitors, isocitrate dehydrogenase 1/2 mutation inhibitors, and Bcl-2 inhibitor. Despite that, the cure for AML remains an unmet clinical need in most patients. AREAS COVERED: The review aims to present new, not yet registered drugs for AML. We searched the English literature for articles concerning AML, targeted drugs, menin inhibitors, DOT1L, BET, IDH inhibitors, FLT3, hedgehog inhibitors, Polo-like kinase inhibitors, RNA splicing, and immune therapies via PubMed. Publications from January 2000 to August 2022 were scrutinized. Additional relevant publications were obtained by reviewing the references from the chosen articles and Google search. Conference proceedings from the previous 5 years of The American Society of Hematology, the European Hematology Association, and the American Society of Clinical Oncology were searched manually. Additional relevant publications were obtained by reviewing the references. EXPERT OPINION: For several years, the therapeutic approach in AML has become more individualized. Novel groups of drugs give hope for greater curability. High response rates have agents that restore the activity of the p53 protein. In addition, agents that work independently of a particular mutation seem promising for AML without any known mutation.


Asunto(s)
Antineoplásicos , Leucemia Mieloide Aguda , Humanos , Proteínas Hedgehog/genética , Proteínas Hedgehog/uso terapéutico , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Inhibidores Enzimáticos/uso terapéutico , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , Tirosina Quinasa 3 Similar a fms/genética , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Mutación
5.
Biopsychosoc Med ; 17(1): 1, 2023 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-36658586

RESUMEN

BACKGROUND: The introduction of BCR-ABL tyrosine kinase inhibitors (TKIs) to chronic myeloid leukemia (CML) therapy has revolutionized the treatment of this disease. Although regular TKI intake is a prerequisite for successful therapy, it has been shown that a significant proportion of patients are non-compliant. Recently there is growing evidence that personality traits may influenced the tendency for non-adherence to treatment in patients with chronic diseases. As far as we know, such a relationship in patients with CML has not been examined, yet. The aim of our study was to determine if personality traits favor non-adherence to treatment recommendations. We investigated the relationship between five-factor model personality factors (conscientiousness, neuroticism, agreeableness, extraversion, and openness) and medication non-adherence. We also checked if the patients with type A and type D personality, were at higher risk of poor medication adherence. METHODS: The following tools were used: self-constructed survey, the NEO-Five Factor Inventory, the Framingham Type A Scale, the D-Scale 14. The study included 140 CML patients treated with imatinib, dasatinib, or nilotinib. RESULTS: 39% of patients reported skipping at least one dose of medication in the month prior to follow-up visit. 51% admitted to skipping such doses from the start of their treatment to the time at which our assessment was performed. We did not find any relationship between the mean values of the analyzed factors of the Big Five (neuroticism, extraversion, openness, agreeableness, conscientiousness) and adherence. However, our analysis revealed that CML patients who admitted to missing doses of drugs during the entire course of treatment demonstrated greater intensity of type A personality traits (p = 0.020). Regarding both factors of type D personality, it was revealed that higher level of negative affectivity significantly decreased the adherence (p = 0.020). CONCLUSION: The results of our study indicate that screening for type D and A personalities may help to identify patients who are at higher risk of poor medication adherence.

6.
Clin Lymphoma Myeloma Leuk ; 23(1): e19-e26, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36396583

RESUMEN

INTRODUCTION: Ruxolitinib is widely used in myelofibrosis (MF). However, some patients do not optimally respond and require more efficacious treatment. Our analysis aimed to establish predictors of ruxolitinib response. PATIENTS AND METHODS: We designed a multicenter, retrospective analysis of the efficacy of ruxolitinib treatment in patients with MF in 15 Polish hematology centers. As responses to ruxolitinib occur within the first 6 months, we used this point to evaluate the efficacy of treatment. Symptoms response was defined as ≥50% reduction of the MF constitutional symptoms assessed by Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS). Spleen response was defined as ≥50% reduction of the difference between the spleen's baseline length and the upper limit norm measured by ultrasonography. RESULTS: 320 MF patients were enrolled. At 6 months of therapy, the spleen response was detected in 140 (50%) patients, and symptoms response in 241 patients (76%). Multivariable analysis identified leukocytosis <25 G/L (OR 2.06, 95%CI: 1.12-3.88, P = .0200), and reticulin fibrosis MF 1 (OR 2.22, 95%CI: 1.11-4.46, P = .0249) contributed to better spleen response. The time interval between MF diagnosis and ruxolitinib administration shorter than 3 months, and platelets ≥150 G/L (OR 1.69, 95% CI 1.01-2.83, P = .0466) influenced symptoms response. CONCLUSION: Establishing predictive factors for ruxolitinib response is particularly important given the potential for new therapies in MF. In patients with a low likelihood of responding to ruxolitinib, using other JAK inhibitors or adding a drug with a different mechanism of action to ruxolitinib may be of clinical benefit.


Asunto(s)
Leucemia , Mielofibrosis Primaria , Humanos , Adulto , Mielofibrosis Primaria/diagnóstico , Mielofibrosis Primaria/tratamiento farmacológico , Estudios Retrospectivos , Polonia , Sistema de Registros
7.
Front Oncol ; 12: 952640, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36212403

RESUMEN

Introduction: Functional single-nucleotide polymorphisms (SNPs) in genes regulating cellular uptake, elimination, and metabolism of xenobiotics may potentially influence the outcome of chronic myeloid leukemia (CML) patients treated with BCR-ABL1 tyrosine kinase inhibitors (TKI). Dasatinib, a second-generation TKI, is a substrate of the ABC-superfamily xenobiotic transporters ABCB1 (MDR1, Pg-P) and ABCG2 (BCRP). Pregnane X receptor (PXR, NR1I2) and constitutive androstane receptor (CAR, NR1I3) are involved in the control of expression of ABCB1 and ABCG2. Aim of the study: In this study, we assessed the impact of inherited variants in ABCB1, ABCG2, PXR, and CAR genes on dasatinib efficacy and toxicity in CML. Materials and methods: Sixty-one tagging SNPs in ABCB1, ABCG2, PXR, and CAR genes were analyzed by real-time quantitative PCR with specific probes in 86 CML patients who failed imatinib therapy. Results: We found the associations between SNPs rs7787082 (ABCB1, OR = 0.2; 95% CI = 0.06-0.66, p = 0.008), rs12505410 (ABCG2, OR = 3.82; 95% CI = 1.38-10.55; p = 0.010), and rs3114018 (ABCG2, OR = 0.24; 95% CI = 0.08-0.71; p = 0.010) and the probability of achieving CCyR. Furthermore, progression-free survival (PFS) was significantly influenced by SNPs rs3732357 (HR = 0.2, 95% CI = 0.26-0.70; p = 0.001), rs3732360 (HR = 0.59; 95% CI = 0.38-0.93; p = 0.020), rs11917714 (HR = 0.58; 95% CI = 0.36-0.92; p = 0.020), and rs3732359 (HR = 0.57; 95% CI = 0.36-0.91; p = 0.024) in PXR; rs2307418 (HR = 2.02; 95% CI = 1.19-3.43; p = 0.048) in CAR; and rs2235023 (HR = 2.49; 95% CI = 1.13-5.50; p = 0.011) and rs22114102 (HR = 1.90; 95% CI = 1.00-3.63; p = 0.028) in ABCB1. Moreover, overall survival (OS) was impacted by rs3842 (HR = 1.84; 95% CI = 1.01-3.33; p = 0.012) and rs2235023 (HR = 2.28; 95% CI = 1.03 = 5.02; p = 0.027) in ABCB1, rs11265571 (HR = 1.59; 95% CI = 0.82-3.08; p = 0.037) and rs2307418 (HR = 73.68; 95% CI = 4.47-1215.31; p = 0.003) in CAR, and rs3732360 (HR = 0.64; 95% CI = 0.40 = 1.04; p = 0.049) in PXR. Taking into account the influence of the tested SNPs on treatment toxicity, we found a significant relationship between allele G of polymorphism in the ABCB1 rs7787082 (OR = 4.46; 95% CI = 1.38-14.39 p = 0.012) and hematological complications assuming the codominant gene inheritance model as well as a significant correlation between the presence of minor allele (G) of SNP rs2725256 in the ABCG2 gene (OR = 4.71; 95% CI = 1.20-18.47; p = 0.026) and the occurrence of non-hematological complications assuming a recessive gene inheritance model. Conclusion: Our data suggest that inherited variants in the genes encoding for proteins involved in the transport of xenobiotics may modify the toxicity and efficacy of dasatinib therapy in CML patients.

8.
J Clin Med ; 11(19)2022 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-36233774

RESUMEN

Lenalidomide-based regimens are effective treatment options for patients with relapsed/refractory multiple myeloma (RRMM). However, they are associated with an increased risk of infectious complications. This study examines the clinical factors influencing the occurrence of infection in MM patients treated with lenalidomide and dexamethasone (Rd). A retrospective analysis of all patients who received the Rd regimen between 2017 and 2021 at our institution was performed. The study group consisted of 174 patients and the median age was 65 years. Most patients (n = 110, 63.2%) received the Rd treatment in second-line treatment. The majority of patients (64.3%) received bortezomib-based regimens in the first line of treatment. The median progression-free survival was 12.6 (95% CI: 9.5-16.2) months, and the median overall survival was 22.3 (95% CI: 15.9-28.6) months. The overall response rate was 64.1%, 12.7% of patients achieved complete response, and 20.4% had a very good partial response. In multivariate logistic regression analysis, hypoalbuminemia (OR 4.2, 95% CI: 1.6-11.2, p = 0.0039), autologous hematopoietic stem cell transplantation (AHSCT) before Rd (OR 2.6, 95% CI: 1.0-6.7, p = 0.048), and anemia grade ≥3 (OR 5.0, 95% CI: 1.8-14.0, p = 0.002) were independent factors related to the occurrence of infections. In conclusion, in this large cohort of RRMM patients, AHSCT before Rd regimen therapy, hypoalbuminemia, and anemia during treatment were identified as three independent factors influencing the frequency of infections during Rd therapy. Patients with established risk factors may benefit from optimal supportive therapy.

9.
Blood Adv ; 6(17): 5171-5183, 2022 09 13.
Artículo en Inglés | MEDLINE | ID: mdl-35802458

RESUMEN

Myeloproliferative neoplasms (MPNs) are uncommon in children/young adults. Here, we present data on unselected patients diagnosed before 25 years of age included from 38 centers in 15 countries. Sequential patients were included. We identified 444 patients, with median follow-up 9.7 years (0-47.8). Forty-nine (11.1%) had a history of thrombosis at diagnosis, 49 new thrombotic events were recorded (1.16% patient per year [pt/y]), perihepatic vein thromboses were most frequent (47.6% venous events), and logistic regression identified JAK2V617F mutation (P = .016) and hyperviscosity symptoms (visual disturbances, dizziness, vertigo, headache) as risk factors (P = .040). New hemorrhagic events occurred in 44 patients (9.9%, 1.04% pt/y). Disease transformation occurred in 48 patients (10.9%, 1.13% pt/y), usually to myelofibrosis (7.5%) with splenomegaly as a novel risk factor for transformation in essential thrombocythemia (ET) (P= .000) in logistical regression. Eight deaths (1.8%) were recorded, 3 after allogeneic stem cell transplantation. Concerning conventional risk scores: International Prognostic Score for Essential Thrombocythemia-Thrombosis and new International Prognostic Score for Essential Thrombocythemia-Thrombosis differentiated ET patients in terms of thrombotic risk. Both scores identified high-risk patients with the same median thrombosis-free survival of 28.5 years. No contemporary scores were able to predict survival for young ET or polycythemia vera patients. Our data represents the largest real-world study of MPN patients age < 25 years at diagnosis. Rates of thrombotic events and transformation were higher than expected compared with the previous literature. Our study provides new and reliable information as a basis for prospective studies, trials, and development of harmonized international guidelines for the specific management of young patients with MPN.


Asunto(s)
Trastornos Mieloproliferativos , Policitemia Vera , Mielofibrosis Primaria , Trombocitemia Esencial , Trombosis , Adulto , Niño , Humanos , Trastornos Mieloproliferativos/complicaciones , Trastornos Mieloproliferativos/diagnóstico , Trastornos Mieloproliferativos/epidemiología , Policitemia Vera/complicaciones , Mielofibrosis Primaria/genética , Estudios Prospectivos , Trombosis/etiología , Adulto Joven
10.
Clin Lymphoma Myeloma Leuk ; 22(6): 405-415, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-34933827

RESUMEN

INTRODUCTION: Tyrosine kinase inhibitors (TKIs) have greatly improved the treatment outcome for most patients with chronic myeloid leukemia (CML). Ponatinib is a new pan-inhibitor of TK active in resistant CML. This study aimed to evaluate the efficacy and safety of ponatinib in patients suffering from CML. PATIENTS AND METHODS: This multicenter, non-randomized, observational, retrospective study evaluated the efficacy and safety of ponatinib administered in adult CML patients in any disease phase, including those with a detected ABL T315I mutation, which were resistant or intolerant to previous-generation TKIs. The study comprised 43 patients benefiting from the ponatinib donation program who were treated in 16 Polish centers. RESULTS: For patients who started treatment with ponatinib in chronic phase (CP) (n = 23) and in accelerated phase (AP) (n = 3) the median time on ponatinib was 19.5 months (range: 1.0-35.4), and 31.7 months (range: 31.0-34.1), respectively. All these patients were in CP after 1 month of treatment and at the end of observation - none of them progressed to AP or blastic phase (BP) during the study, meaning that progression-free survival was 100% at the end of observation (35.4 months). The estimated 2-year survival in this group of patients was 84%. For all 43 patients, median survival was not reached (lower quartile 6.3 months), and estimated 2-year survival was 60%. CONCLUSION: Our analysis confirmed ponatinib efficacy in a significant proportion of patients heavily pre-treated with TKIs achieving durable responses in both CP and AP/BP CML groups.


Asunto(s)
Antineoplásicos , Leucemia Mielógena Crónica BCR-ABL Positiva , Adulto , Antineoplásicos/uso terapéutico , Resistencia a Antineoplásicos , Humanos , Imidazoles , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Polonia , Inhibidores de Proteínas Quinasas/efectos adversos , Piridazinas , Estudios Retrospectivos
11.
Eur J Haematol ; 107(1): 129-136, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33764578

RESUMEN

OBJECTIVES: Relapse of myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) belongs to the major causes of treatment failure. METHODS: Retrospective multicenter analysis of patients diagnosed with AML or MDS who had hematological relapse after allo-HSCT and were treated with azacitidine for this indication. RESULTS: Twenty-three patients receiving azacitidine as the first treatment of relapse (Group_1) and 8 patients receiving azacitidine after other treatment of relapse (Group_2) were included. There were 68% males, median age at initiation of azacitidine was 53 years (15-66). Median time to relapse was 3.5 months and 6.3 months in Group_1 and Group_2, respectively; median time from relapse to azacitidine 0.2 and 2.3 months. Azacitidine 75 mg/m2 , days 1-7, was administered in 78% and 75% of patients in Group_1 and Group_2, concomitant DLI in 48% and 50%. With median follow-up of 4.7 and 13.6 months, the median overall survival was 5.9 and 9.5 months. 17% and 37.5% patients proceeded to salvage allo-HSCT, with median OS of 11.6 months and not reached respectively. CONCLUSIONS: Azacitidine treatment for hematological relapse is associated with poor outcome; nevertheless, a proportion of patients may benefit from it, including patients receiving subsequent salvage allo-HSCT.


Asunto(s)
Azacitidina/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/métodos , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/terapia , Síndromes Mielodisplásicos/tratamiento farmacológico , Síndromes Mielodisplásicos/terapia , Recurrencia Local de Neoplasia/tratamiento farmacológico , Trasplante Homólogo/métodos , Adolescente , Adulto , Anciano , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento , Adulto Joven
12.
Int J Cancer ; 148(7): 1616-1624, 2021 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-33038278

RESUMEN

Myeloproliferative neoplasms (MPNs) are a group of diseases that cause myeloid hematopoietic cells to overproliferate. Epidemiological and familial studies suggest that genetic factors contribute to the risk of developing MPN, but the genetic susceptibility of MPN is still not well known. Indeed, only few loci are known to have a clear role in the predisposition to this disease. Some studies reported a diagnosis of MPNs and multiple myeloma (MM) in the same patients, but the biological causes are still unclear. We tested the hypothesis that the two diseases share at least partly the same genetic risk loci. In the context of a European multicenter study with 460 cases and 880 controls, we analyzed the effect of the known MM risk loci, individually and in a polygenic risk score (PRS). The most significant result was obtained among patients with chronic myeloid leukemia (CML) for PS0RS1C1-rs2285803, which showed to be associated with an increased risk (OR = 3.28, 95% CI 1.79-6.02, P = .00012, P = .00276 when taking into account multiple testing). Additionally, the PRS showed an association with MPN risk when comparing the last with the first quartile of the PRS (OR = 2.39, 95% CI 1.64-3.48, P = 5.98 × 10-6 ). In conclusion, our results suggest a potential common genetic background between MPN and MM, which needs to be further investigated.


Asunto(s)
Predisposición Genética a la Enfermedad , Mieloma Múltiple/genética , Trastornos Mieloproliferativos/genética , Anciano , Femenino , Sitios Genéticos , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Factores de Riesgo
13.
Blood Cancer J ; 10(8): 89, 2020 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-32873778

RESUMEN

Telomere length measured in leukocyte (LTL) has been found to be associated with the risk of developing several cancer types, including myeloproliferative neoplasms (MPNs). LTL is genetically determined by, at least, 11 SNPs previously shown to influence LTL. Their combination in a score has been used as a genetic instrument to measure LTL and evaluate the causative association between LTL and the risk of several cancer types. We tested, for the first time, the "teloscore" in 480 MPN patients and 909 healthy controls in a European multi-center case-control study. We found an increased risk to develop MPNs with longer genetically determined telomeres (OR = 1.82, 95% CI 1.24-2.68, P = 2.21 × 10-3, comparing the highest with the lowest quintile of the teloscore distribution). Analyzing the SNPs individually we confirm the association between TERT-rs2736100-C allele and increased risk of developing MPNs and we report a novel association of the OBFC1-rs9420907-C variant with higher MPN risk (ORallelic = 1.43; 95% CI 1.15-1.77; P = 1.35 × 10-3). Consistently with the results obtained with the teloscore, both risk alleles are also associated with longer LTL. In conclusion, our results suggest that genetically determined longer telomeres could be a risk marker for MPN development.


Asunto(s)
Trastornos Mieloproliferativos/genética , Polimorfismo de Nucleótido Simple , Homeostasis del Telómero , Anciano , Femenino , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Trastornos Mieloproliferativos/etiología , Factores de Riesgo
15.
Med Oncol ; 34(6): 104, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28444623

RESUMEN

Failure to comply with treatment recommendations is very common in patients, but still poorly recognised by doctors. The current practice of using oral therapy on a large scale has been increasingly adopted for cancer patients. Chronic myeloid leukaemia (CML) is just such an example, where the introduction of taking new oral medications, the tyrosine kinase BCR-ABL inhibitors (TKI), has now revolutionised the treatment. The aim of our study was to assess treatment adherence in a group of Polish CML patients (a survey was conducted on 140 patient aged ≥18 years) treated with oral TKI (imatinib, dasatinib and nilotinib) taking into account the following variables: gender, age, education, place of residence, family circumstances and duration of therapy. In addition, we evaluated whether there is a relationship between how patients perceive their level of adherence to treatment recommendations with how subjectively the required dosage regimen was followed. Half the patients admitted to skipping at least one drug dose during the entire course of treatment and 39% did so within their last treatment month. Patients were also found to overestimate their own adherence assessment; around 60% of those missing at least 1 drug dose within the last treatment month believed they 'always' followed recommendations. The study demonstrated that adherence deteriorates over time. Furthermore, patients aged >65 years and patients suffering at least one comorbid disease had better adherence (p < 0.011). There were no differences in adherence among patients treated with imatinib, dasatinib and nilotinib (p = 0.249).


Asunto(s)
Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/epidemiología , Cumplimiento de la Medicación/estadística & datos numéricos , Inhibidores de Proteínas Quinasas/uso terapéutico , Adulto , Anciano , Antineoplásicos/uso terapéutico , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proteínas Tirosina Quinasas , Encuestas y Cuestionarios
17.
Clin Lymphoma Myeloma Leuk ; 17(5): 283-295, 2017 05.
Artículo en Inglés | MEDLINE | ID: mdl-28185798

RESUMEN

INTRODUCTION: The aim of this study was to evaluate quality of life (QOL) and adherence to the therapy in patients with chronic myeloid leukemia in chronic phase treated with nilotinib as second-line therapy. PATIENTS AND METHODS: A multicenter, prospective, observational trial with 6 time points was conducted; 177 patients were recruited in 23 centers in Poland who were treated with nilotinib as second-line therapy because of the ineffectiveness or intolerance of their previous therapy. QOL was evaluated with the standard European Organization for Research and Treatment of Cancer Core Quality of Life questionnaire. Adherence to the therapy was assessed using the 4-item Morisky Medication Adherence Scale by patients and their physicians. RESULTS: The average QOL in patients who completed the study was significantly higher during the last visit (69.4 ± 17.4) than at the start of the study (59.1 ± 18.8; P < .001). At their first visit, 120 (83.2%) patients assessed themselves as highly compliant and 135 (93.4%) at the fifth visit. Low-compliance patients represented 3 (1.7% of the total) during visit 1; none of the patients self-assessed as low compliance since the fourth visit. At the first visit 151 (85.3%) patients were categorized by their physicians as highly compliant and 138 (96.0%) during the last 3 visits. Patients' and their physicians' assessments were significantly correlated. CONCLUSION: The QOL among patients receiving nilotinib administered as second-line therapy was very good and adherence to the treatment was high. The efficacy and safety of the drug were confirmed in the real-life setting.


Asunto(s)
Antineoplásicos/uso terapéutico , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Cumplimiento de la Medicación/estadística & datos numéricos , Pirimidinas/uso terapéutico , Calidad de Vida , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/tratamiento farmacológico , Estudios Prospectivos , Terapia Recuperativa/métodos , Encuestas y Cuestionarios
18.
Leuk Lymphoma ; 56(8): 2309-14, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25563556

RESUMEN

We retrospectively analyzed the rates of significant non-hematological adverse events (AEs) in 105 patients with chronic myeloid leukemia (CML) treated with second-generation tyrosine kinase inhibitor (TKIs) dasatinib or nilotinib used as second-line therapy in Polish tertiary care centers. Our analysis revealed that in a "real life setting," nearly half of patients with CML on second-generation TKIs suffer from therapy complications. Grade 2-5 non-hematological AEs were observed in 40% of patients treated with nilotinib and in 42% treated with dasatinib (p=0.83). Severe vascular events including peripheral artery occlusive disease (PAOD) occurred in 11% of patients on nilotinib and 4% on dasatinib (p=0.16). Pleural effusion occurred more often in the dasatinib group (26%) than in the nilotinib group (2%) (p=0.003). Importantly, most AEs occurred late, after more than 1 year of treatment. Since AEs are most often the reason for poor therapy compliance, careful monitoring of tolerability is crucial for an optimal treatment response in CML.


Asunto(s)
Antineoplásicos/efectos adversos , Dasatinib/efectos adversos , Leucemia Mielógena Crónica BCR-ABL Positiva/complicaciones , Enfermedades Vasculares Periféricas/etiología , Inhibidores de Proteínas Quinasas/efectos adversos , Pirimidinas/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Dasatinib/uso terapéutico , Sustitución de Medicamentos , Femenino , Estudios de Seguimiento , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/mortalidad , Masculino , Persona de Mediana Edad , Derrame Pleural/etiología , Inhibidores de Proteínas Quinasas/uso terapéutico , Pirimidinas/uso terapéutico , Retratamiento , Estudios Retrospectivos , Insuficiencia del Tratamiento , Resultado del Tratamiento , Adulto Joven
19.
Blood Cells Mol Dis ; 54(2): 139-43, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25488616

RESUMEN

Vascular endothelial growth factor type A (VEGFA) is a key regulator of angiogenesis and vascular permeability. Chronic lymphocytic leukemia (CLL) cells are able to secrete VEGFA and express VEGFA receptors, thus it can be hypothesized that VEGFA-mediated signaling influences CLL clone survival. In this case-control study we verified whether inherited differences in activities of VEGFA and its main receptor VEGFR2 impact predisposition to CLL or the course of the disease. Four functional single nucleotide polymorphisms (SNPs) including two SNPs in VEGFA gene, namely rs2010963 (+405G>C) and rs3025039 (+936C>T) and two SNPs in VEGFR2 gene including rs7667298 (-271G>A) and rs1870377 (+1719A>T) were genotyped using PCR-based assays in 223 Caucasian CLL patients and 150 matched controls. Regarding VEGF rs2010963 SNP, we observed an association between CLL and allele C distribution with an OR of 1.52 (95% CI, 1.002-2.312), p=0.04. The distribution of other genotypes and alleles was similar in CLL and control groups. No genotype or allele was significantly associated with important prognostic factors in CLL including clinical stage, IgVH mutational status, ZAP-70 expression and FISH cytogenetic abnormalities. In conclusion, the results of our study indicate that genetic polymorphisms in VEGFA mediated pathway may influence the susceptibility to CLL.


Asunto(s)
Leucemia Linfocítica Crónica de Células B/genética , Polimorfismo de Nucleótido Simple , Factor A de Crecimiento Endotelial Vascular/genética , Receptor 2 de Factores de Crecimiento Endotelial Vascular/genética , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Estudios de Casos y Controles , Femenino , Expresión Génica , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Cadenas Pesadas de Inmunoglobulina/genética , Leucemia Linfocítica Crónica de Células B/patología , Desequilibrio de Ligamiento , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Población Blanca , Proteína Tirosina Quinasa ZAP-70/genética
20.
Przegl Lek ; 71(5): 289-95, 2014.
Artículo en Polaco | MEDLINE | ID: mdl-25248246

RESUMEN

A cancer diagnosis provides significantly level of emotional distress and discomfort both for patient and his family. They must confront themselves with the new, difficult reality. A cancer-related distress may promote the serious psychic disturbances and influenced negatively the therapeutic process. The good interpersonal relationship between physician and patient clearly decreased the level of fear and depression, improved patient's physical and psychical state. Patients who have good communication with their physician are more prone to good adherence and compliance which are essential for the effective therapeutic process. This article discusses the role of relationship between physician and patient regarding its influence on compliance and provides a review of different types of therapeutic contact and the principles of building the physician-patient relationship.


Asunto(s)
Neoplasias Hematológicas/psicología , Neoplasias Hematológicas/terapia , Cooperación del Paciente , Relaciones Médico-Paciente , Comunicación , Humanos
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...