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1.
Acta Haematol ; 146(4): 277-286, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37015191

RESUMEN

INTRODUCTION: Both microenvironmental signals from surrounding cells and changes in the genome of leukemic cells play essential role in the development of chronic lymphocytic leukemia. Nurse-like cells (NLCs) are one of the important elements of the microenvironment of CLL cells. The key role in the interactions of leukemic cells with NLCs is played by chemokines, which may interfere with the programmed cell death process in the leukemic lymphocytes. The aim of our study was analysis of selected microenvironmental factors having a potential impact on the leukemic cells survival, as well as their association with clinical, cytogenetic, and molecular parameters. For this study, we selected three types of molecules which can modulate microenvironment: chemokines IL-8 and CCL3 (which are classically secreted to extracellular matrix), soluble forms of adhesion molecules JAG1 and CD163, and secreted form of endogenous protein BIRC5. We assessed their expression in the serum of CLL patients as well as in medium of long-term NLCs cultures. METHODS: Long-term cell culture was prepared from mononuclear cells derived from the blood of 34 patients with CLL. Number of NLCs cells was evaluated, under a light inverted microscope. The concentration of IL-8, CCL3, sBIRC5, sCD163, and sJAG1 in culture medium and serum was assessed by enzyme-linked immunosorbent assays. RESULTS: There were significant differences in the concentration of IL-8, sBIRC5, CCL3, sCD163, and sJAG1 between the patient's blood serum and the culture medium. The concentrations of IL-8, CCL3, and JAG1 were higher in the culture medium, which confirmed the role of the microenvironment in the production of these proteins. In addition, the concentration of CCL3 chemokine in both patient's blood serum and in the culture medium correlated with the number of NLCs and with known prognostic factors in the course of CLL, e.g., Rai stage, WBC, expression of ZAP-70, CD38, and CD5/19. CONCLUSION: The microenvironment of CLL cells, which includes NLCs, plays an important role in the pathogenesis of CLL. The CCL3 chemokine seems to be a good factor representing microenvironment of CLL cells. Chronic lymphocytic leukemia is a complex and very heterogeneous disease; therefore, its progress should be considered both in the context of genetic changes and the interaction with microenvironmental cells.


Asunto(s)
Leucemia Linfocítica Crónica de Células B , Humanos , Quimiocina CCL3/genética , Quimiocina CCL3/metabolismo , Ensayo de Inmunoadsorción Enzimática , Interleucina-8 , Leucemia Linfocítica Crónica de Células B/diagnóstico , Leucemia Linfocítica Crónica de Células B/genética , Leucemia Linfocítica Crónica de Células B/metabolismo , Pronóstico , Microambiente Tumoral/genética
2.
Am J Hematol ; 95(6): 604-611, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32096887

RESUMEN

In recent years, considerable progress has been made in frontline therapy for elderly/physically unfit patients with CLL. The combination of obinutuzumab and chlorambucil (O-Clb) has been shown to prolong progression free survival (PFS, median PFS-31.5 months) and overall survival (OS) compared to chlorambucil alone. More recently, obinutuzumab given in combination with either ibrutinib or venetoclax improved PFS but not OS when compared to O-Clb. In this retrospective multinational, multicenter co-operative study, we evaluated the efficacy and safety of frontline treatment with O ± Clb in unfit patients with CLL, in a "real-world" setting. Patients with documented del (17p13.1)/TP53 mutation were excluded. A total of 437 patients (median age, 75.9 years; median CIRS score, 8; median creatinine clearance, 61.1 mL/min) were included. The clinical overall response rate was 80.3% (clinical complete and partial responses in 38.7% and 41.6% of patients, respectively). Median observation time was 14.1 months and estimated median PFS was 27.6 months (95% CI, 24.2-31.0). In a multivariate analysis, high-risk disease [del (11q22.3) and/or IGHV-unmutated], lymph nodes of diameter > 5 cm, obinutuzumab monotherapy and reduced cumulative dose of obinutuzumab, were all independently associated with shorter PFS. The median OS has not yet been reached and estimated 2-year OS is 88%. In conclusion, in a "real-world" setting, frontline treatment with O-Clb achieves PFS comparable to that reported in clinical trials. Inferior outcomes were noted in patients with del (11q22.3) and/or unmutated IGHV and those treated with obinutuzumab-monotherapy. Thus, O-Clb can be still considered as legitimate frontline therapy for unfit CLL patients with low-risk disease.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Deleción Cromosómica , Cromosomas Humanos Par 17/genética , Leucemia Linfocítica Crónica de Células B , Proteína p53 Supresora de Tumor/genética , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Clorambucilo/administración & dosificación , Clorambucilo/efectos adversos , Supervivencia sin Enfermedad , Femenino , Humanos , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Leucemia Linfocítica Crónica de Células B/genética , Leucemia Linfocítica Crónica de Células B/mortalidad , Masculino , Estudios Retrospectivos , Tasa de Supervivencia
3.
Chemotherapy ; 64(3): 155-162, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31715597

RESUMEN

Bendamustine is a cytostatic drug with a unique structure, combining the features of purine nucleoside analogs and alkylating agents. In patients with chronic lymphocytic leukemia (CLL) it is commonly used in combination with rituximab (BR protocol) both in the first-line as well as subsequent lines of therapy, and in clinical trials it is often combined with new targeted therapies. Therefore, the data on its real-life safety and efficacy are of clinical significance. As the Polish Lymphoma Research Group (PLRG), we retrospectively analyzed the efficacy and tolerability of bendamustine monotherapy in 96 patients with CLL. The median number of bendamustine cycles was 5, and 44 patients did not complete the planned 6 cycles (46%). Among the adverse events associated with the earlier termination of bendamustine treatment, infections were the most common (20.5%), followed by neutropenia (15.9%) and thrombocytopenia (15.9%). Dose reductions and/or delays occurred in 31% of treatment cycles (132 of 425) with neutropenia (17.9%) as the most frequent cause. Efficacy analysis showed an overall response rate of 88.2% with complete remission and partial remission achieved in 43.8 and 41.7% of patients, respectively. At the 24th month of follow-up, progression-free survival was 52% and overall survival was 69.7%. Bendamustine in monotherapy was found to be safe and efficacious, at least in terms of early response. Special attention should be paid to infectious complications, and especially that immune disorders are characteristic in the clinical course of CLL. Our observations suggest efforts must be made to ensure the proper timing and proper dose in the administration of the drug, and to avoid the premature termination of the treatment.


Asunto(s)
Clorhidrato de Bendamustina/uso terapéutico , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Clorhidrato de Bendamustina/efectos adversos , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Humanos , Leucemia Linfocítica Crónica de Células B/mortalidad , Masculino , Persona de Mediana Edad , Neutropenia/etiología , Estudios Retrospectivos , Tasa de Supervivencia , Trombocitopenia/etiología , Resultado del Tratamiento
4.
Neurol Neurochir Pol ; 52(2): 228-234, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-29146406

RESUMEN

Inclusion of the central nervous system (CNS) in the course of chronic lymphocytic leukaemia (CLL) is rare. At the moment no risk factors or proven treatment methods are known. The disease is described both in its early phase and during its acceleration period, thus it has been suggested that there might be independent mechanisms influencing the development of this condition. As there are no unified diagnostic procedure algorithms each patient needs to be assessed individually. CLL can manifest mostly in elderly people, for whom a possibility of development of neurological disorders with their aetiology different from leukaemia, should also be taken into consideration. The thesis presents a group of seven patients with CLL with CNS infiltration. Patients with prolymphocytic leukaemia, Richter's transformation and the original location of leukemic infiltration within the eye socket constitute an especially interesting case.


Asunto(s)
Leucemia Linfocítica Crónica de Células B , Sistema Nervioso Central , Humanos , Factores de Riesgo
5.
Neurol Neurochir Pol ; 52(3): 410-414, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29703403

RESUMEN

Secondary nervous system lymphoma (SCNSL) is a rare extranodal form of non-Hodgkin lymphoma (NHL). This applies to a particular form of lymphoma that does not originally derive from the central nervous system (CNS); it can be both an isolated form of relapse or a systemic part of disease progression. Due to poor prognosis and a lack of established algorithms of therapeutic procedures, it is a big challenge for physicians from many specializations. In our study, we present an interesting case of a patient with a relapsed form of SCNSL for whom a unique form of treatment was used - intraventricular administration of rituximab and methotrexate.


Asunto(s)
Neoplasias del Sistema Nervioso Central , Linfoma no Hodgkin , Humanos , Recurrencia Local de Neoplasia
6.
Ann Hematol ; 96(1): 33-50, 2017 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-27730344

RESUMEN

Expression of microRNAs is altered in cancer. Circulating miRNA level assessed in body fluids commonly reflects their expression in tumor cells. In leukemias, however, both leukemic and nonleukemic cells compose circulating miRNA expression profile of peripheral blood. The latter contribution to extracellular miRNA pool may result in specific microenvironmental signaling, which promotes proliferation and survival. In our study, we used qT-PCR to assay peripheral blood serum of 22 chronic lymphocytic leukemia (CLL) patients for the expression of 84 miRNAs associated with activation and differentiation of B and T lymphocytes. Results were analyzed regarding the most important prognostic factors. We have found that the general expression of examined miRNAs in CLL patients was lower as compared to healthy volunteers. Only miR-34a-5p, miR31-5p, miR-155-5p, miR-150-5p, miR-15a-3p, and miR-29a-3p were expressed on a higher level. Alterations of expression observed in CLL patients involved miRNAs associated both with B and T lymphocyte differentiation and activation. The most important discriminating factors for all functional miRNA groups were trisomy 12, CD38 expression, B2M level, WBC, and NOTCH1 gene mutation. Correlation of expression of miRNAs related to T lymphocytes with prognostic factors proves their supportive function in a leukemic microenvironment. Further studies utilizing a larger test group of patients may warrant the identification of circulating miRNAs that are key players in intercellular interactions and should be considered in the design of microenvironment-targeted therapies.


Asunto(s)
Linfocitos B/fisiología , Diferenciación Celular/fisiología , Regulación Neoplásica de la Expresión Génica , Leucemia Linfocítica Crónica de Células B/sangre , MicroARNs/sangre , Linfocitos T/fisiología , Anciano , Anciano de 80 o más Años , Secuencia de Bases , Células Cultivadas , Femenino , Humanos , Leucemia Linfocítica Crónica de Células B/diagnóstico , Leucemia Linfocítica Crónica de Células B/genética , Masculino , MicroARNs/biosíntesis , MicroARNs/genética , Persona de Mediana Edad
7.
Neurol Neurochir Pol ; 51(4): 319-323, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28476199

RESUMEN

Primary central nervous system lymphoma (PCNSL) comprises around 3-5% of primary central nervous system (CNS) tumours and around 1% of all non-Hodgkin lymphoma (NHL). Diffuse large B-cell lymphoma (DLBCL) is the most common histological type. High effectiveness of chemo- and radiotherapy for PCNSL regrettably does not eliminate significant risks of recurrence for CNS tumours. That results in higher interest in other treatment options, including surgical procedures. PCNSL remains in the scope of interest for many specialists and neurosurgeons seem to play a more important role.


Asunto(s)
Antineoplásicos/administración & dosificación , Neoplasias del Sistema Nervioso Central/terapia , Glucocorticoides/uso terapéutico , Linfoma/terapia , Procedimientos Neuroquirúrgicos , Radiocirugia , Antineoplásicos/uso terapéutico , Humanos , Inyecciones Intraventriculares , Inyecciones Espinales , Linfoma de Células B Grandes Difuso/terapia , Linfoma no Hodgkin/terapia , Técnicas Estereotáxicas
8.
Leuk Lymphoma ; 65(2): 175-186, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37921067

RESUMEN

Richter transformation (RT) is defined as developing an aggressive lymphoma in 2-10% of patients suffering from chronic lymphocytic leukemia (CLL). So far, no complex analysis of RT demographics and treatment outcomes has been performed in Poland. Thus, the retrospective analysis of 124 patients with RT from Polish hematology centers was designed. Ninety-nine patients with diffuse large B-cell lymphoma (DLBCL-RT) were identified. The median overall survival (OS) for DLBCL-RT was 17.3 months, while for Hodgkin lymphoma (HL-RT)-21.3 months. In multivariate analysis, the independent factors of worse OS for DLBCL-RT were: prior CLL therapy, ECOG stage ≥2, and elevated serum LDH activity. Patients who proceeded to hematopoietic stem cell transplantation (HSCT) achieved better results. The median OS in allogeneic HSCT recipients was not reached, while in autologous HSCT median OS was 51.3 months. In conclusion, our study represents the largest dataset of patients diagnosed with RT in Poland and confirms its dismal prognosis.


Asunto(s)
Leucemia Linfocítica Crónica de Células B , Linfoma de Células B Grandes Difuso , Adulto , Humanos , Leucemia Linfocítica Crónica de Células B/patología , Polonia , Estudios Retrospectivos , Resultado del Tratamiento , Pronóstico , Linfoma de Células B Grandes Difuso/patología , Transformación Celular Neoplásica/patología
9.
Blood Cells Mol Dis ; 50(4): 263-70, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23313631

RESUMEN

B-cell chronic lymphocytic leukemia (B-CLL) is one of the most common hematologic malignancies in Western countries. Accumulation of leukemic lymphocytes in peripheral blood, bone marrow and secondary lymphatic organs of CLL patients is due to decreased apoptosis rather than to increased proliferation. The former is driven by signals from a specific microenvironment, created by stromal cells of mesenchymal origin, follicular dendritic cells, T lymphocytes and others. Nurse-like cells (NLCs) were first described to differentiate from peripheral blood mononuclear cells of CLL patients in vitro, then they have been also found in proliferation centers of their lymphatic tissues. Like tumor-associated macrophages (TAMs) in solid tumors, nurse-like cells promote survival of CLL lymphocytes. NLC gene expression patterns suggest their similarity to TAMs and differ between patients depending on ZAP70 protein expression status. NLC number in vitro corresponds with CD14 expressing cell count and beta-2-microglobulin serum level, and positively correlates with leukemic lymphocyte viability. As NLCs strongly express genes for adhesion molecules and secrete chemokines of antiapoptotic activity, they should be considered as a target for anti-microenvironment therapy of this incurable disease.


Asunto(s)
Leucemia Linfocítica Crónica de Células B/patología , Macrófagos/patología , Microambiente Tumoral , Adulto , Anciano , Anciano de 80 o más Años , Apoptosis , Supervivencia Celular/genética , Supervivencia Celular/inmunología , Femenino , Regulación Leucémica de la Expresión Génica , Humanos , Leucemia Linfocítica Crónica de Células B/genética , Leucemia Linfocítica Crónica de Células B/inmunología , Leucemia Linfocítica Crónica de Células B/mortalidad , Recuento de Leucocitos , Macrófagos/inmunología , Macrófagos/metabolismo , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Fagocitosis/inmunología , Pronóstico , Transcriptoma , Microambiente Tumoral/genética , Microambiente Tumoral/inmunología
10.
Adv Clin Exp Med ; 32(1): 131-136, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36603138

RESUMEN

BACKGROUND: The first-line obinutuzumab-based immunochemotherapy improves the outcome of patients with follicular lymphoma (FL) compared with rituximab-based regimens. However, infusion-related reactions occur in almost half of patients during the 1st obinutuzumab administration. OBJECTIVES: The study aimed to evaluate the early effectiveness and safety of obinutuzumab-based induction regimens in a real-world setting. MATERIAL AND METHODS: Outcomes of patients diagnosed with FL and treated with obinutuzumab between January 2020 and September 2021 were analyzed. RESULTS: The study group included 143 treatment-naïve patients with FL. The median age was 52 years (range: 28-89 years); 45.1% of patients had a high-risk disease as assessed using the Follicular Lymphoma International Prognostic Index (FLIPI). Induction chemotherapy included: O-CVP (obinutuzumab, cyclophosphamide, vincristine, prednisolone) in 49.0% of patients, O-CHOP (O-CVP plus doxorubicin) in 28.7% and O-BENDA (obinutuzumab, bendamustine) in 22.4%. Complete response (CR) and partial response (PR) rates were 69.9% and 26.5%, respectively. There was no difference in response rates between different regimens (p = 0.309). Maintenance was started in 115 patients (85.2%). In the 1st cycle, obinutuzumab was administered as a single 1000-milligram infusion in 47.9% of patients, whereas in 52.1%, initial infusions were split over 2 days (100 mg/900 mg). Infusion-related reactions were reported only during the 1st administration of obinutuzumab in 9.1% of patients, with a similar incidence in those receiving the total dose on a single day or split over 2 days (p = 0.458). The most common adverse events were hematological. Five patients died from coronavirus disease 2019 (COVID-19). CONCLUSION: The early responses to induction regimens and adverse events profile were similar for every type of induction treatment. The infusion-related reactions were rare and limited to the 1st dose of obinutuzumab.


Asunto(s)
COVID-19 , Linfoma Folicular , Humanos , Persona de Mediana Edad , Linfoma Folicular/tratamiento farmacológico , Linfoma Folicular/etiología , Linfoma Folicular/patología , Rituximab/efectos adversos , Estudios Retrospectivos , Polonia , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Ciclofosfamida/uso terapéutico , Doxorrubicina
11.
Mol Med Rep ; 25(2)2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34981813

RESUMEN

Alterations in microRNA (miRNA/miRs) expression are associated with the occurrence and course of human diseases, including chronic lymphocytic leukemia (CLL). Expression of miRNAs may vary among patients with CLL in different cytogenetic risk groups. The present study assessed the expression levels of the following miRNAs in 35 patients with CLL: hsa­miR­15a, ­16­1, ­29a, ­29c, ­34a, ­34b, ­155, ­181a, ­181b, ­221, ­222 and ­223. Fluorescent in situ hybridization (FISH) analysis was performed for 13q14d, 17p13 and 11q22 deletions and chromosome 12 trisomy. Significantly higher expression levels of miR­181a, ­221 and ­223 were observed in the group at low risk of disease progression (stage 0) compared with the group with high risk of CLL progression (P=0.036, P=0.019 and P=0.038, respectively). The present study revealed that the expression levels of miRNA­181b and miRNA­223 were significantly higher in the group of patients without D13S319 deletion (P=0.039 and P=0.037, respectively). Moreover, the expression levels of miR­15a and miRNA­29c were demonstrated to be significantly higher in the group of patients with CLL who had a tumor protein p53 deletion, identified by FISH, compared with patients without this lesion (P=0.047, P=0.03 respectively). Based on receiver operating characteristic curve analysis, the present study revealed that miR­181a, ­221 and ­223 expression was able to distinguish low and high risk of CLL progression in patients. Among the tested miRNAs, miRNA­181a, ­221 and ­223 were indicated to have the greatest diagnostic potential in CLL.


Asunto(s)
Aberraciones Cromosómicas , Leucemia Linfocítica Crónica de Células B/genética , Leucemia Linfocítica Crónica de Células B/inmunología , Anciano , Deleción Cromosómica , Progresión de la Enfermedad , Femenino , Humanos , Hibridación Fluorescente in Situ , Masculino , MicroARNs/genética , MicroARNs/metabolismo , Persona de Mediana Edad , Curva ROC , Factores de Riesgo , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo
12.
Cancers (Basel) ; 14(3)2022 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-35158826

RESUMEN

BACKGROUND: The severe acute respiratory syndrome coronavirus (SARS-CoV-2) has become the cause of a worldwide pandemic, and its clinical infection course in patients with hematological malignancies may be severe. METHODS: We performed a retrospective study on 188 chronic lymphocytic leukemia patients (CLL) with COVID-19 infection. RESULTS: At the time of infection 51 patients (27.1%) were treated with Bruton tyrosine kinase inhibitor (BTKi), 46 (24.5%) with anti-CD20 antibodies while 37 patients (19.7%) received venetoclax. In total, 111 patients (59.0%) required hospitalization and 50 patients (26.5%) died due to COVID-19. Patients with poor performance status (ECOG >1; p = 0.02), advanced age (>65 years; p = 0.04), low hemoglobin concentration (≤10 g/dl; p = 0.0001), low platelets (<100 × 109/L; p = 0.003), and elevated lactate dehydrogenase level (LDH; p = 0.014) had an increased risk of death due to COVID-19. Neither CLL treatment status (treatment naïve vs. treated) nor the type of CLL-directed treatment had impact on the SARS-CoV-2 related risk of death. The multivariate survival analysis showed that advanced age (p = 0.009) and low platelet count (p = 0.0001) were associated with significantly shorter patients' overall survival. CONCLUSIONS: SARS-CoV-2 infection in CLL patients is associated with poor outcome regardless of administered CLL-directed treatment.

13.
Ann Agric Environ Med ; 28(3): 531-533, 2021 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-34558281

RESUMEN

Acquired haemophilia (AH) is a suddenly occurring severe blood diathesis that affects both males and females and is caused by autoantibodies which inhibit coagulation factor VIII. The report describes an unusual case of acquired haemophilia in which an epileptic seizure and haemorrhage into the ventricular system of the brain were the first manifestations of the disease. In addition, APTT was prolonged to 94.6 seconds and the factor VIII level was as low as 1.5%. The level of anti-FVIII antibody was extremely high - 272BU/ml. The patient did not undergo invasive diagnostic procedure or an operation. Recombinant factor VIIa was used to control the bleeding. In order to eradicate the inhibitor, the patient received prednisone and cyclophosphamide. Complete remission was achieved after 5.5 weeks of treatment.


Asunto(s)
Ventrículos Cerebrales/irrigación sanguínea , Hemofilia A/complicaciones , Convulsiones/etiología , Autoanticuerpos/sangre , Ventrículos Cerebrales/diagnóstico por imagen , Factor VIII/metabolismo , Hemofilia A/diagnóstico por imagen , Hemofilia A/metabolismo , Hemofilia A/patología , Hemorragia/diagnóstico por imagen , Hemorragia/etiología , Hemorragia/patología , Humanos , Masculino , Persona de Mediana Edad , Convulsiones/sangre , Convulsiones/patología
14.
Ann Agric Environ Med ; 28(4): 733-736, 2021 Dec 29.
Artículo en Inglés | MEDLINE | ID: mdl-34969238

RESUMEN

Myelodysplastic syndromes (MDS) are clonal haematopoetic stem cells disorders, characterized by bone marrow dysplasia, ineffecitive haematopoesis and cytopenias. Due to neutropenia, infections are common. A case is presented of a patient with high-risk myelodysplastic syndrome (MDS) complicated by hidradenitis suppurativa that developed in both axillae. Abscesses required multiple incisions and drainage. After five cycles of treatment with azacitidine, the patient underwent allogenic bone marrow transplantation. Unfortunately, six months after the procedure, the patient lost post-transplant chimerism.Treatment with azacitidine was re-started. After the subsequent ten months, blast transformation was observed. Skin lesions in the course of hidradenitis suppurative persisted and were still considerably active.


Asunto(s)
Anemia Refractaria con Exceso de Blastos , Síndromes Mielodisplásicos , Absceso/tratamiento farmacológico , Absceso/etiología , Azacitidina , Humanos , Síndromes Mielodisplásicos/complicaciones
15.
Front Neurol ; 11: 963, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33013640

RESUMEN

The involvement of the central nervous system (CNS) in Hodgkin lymphoma (HL) has been rarely reported, especially in its primary isolated form. Herein, we present a case of a 33-year-old woman, who received immunosuppressive treatment due to ulcerative colitis (at the beginning azathioprine and sulfasalazine, changed to mesalazine), with repetitive episodes of loss of consciousness for a few weeks and with no other symptoms. Magnetic resonance imaging scans of the head revealed a tumor in the lateral part of the left temporal lobe and in the cerebellum. Moreover, a subsequent computed tomographic scan of the chest revealed diffuse tumorous lesions in the lungs. The brain tumor was resected and a tumorous lesion resected from the lungs was biopsied. The histopathological analysis confirmed the final diagnosis of HL localized in the CNS with concomitant pulmonary lymphomatoid granulomatosis (LYG) grade 1. After the patient underwent radiotherapy and chemotherapy, the patient showed complete regression of lesions in the CNS and lungs, which was confirmed by positron emission tomographic scan. LYG and CNS-HL are rare proliferative disease derived from lymphocytes B and associated with EBV infections. An association between LYG and other autoimmune disorders has been reported, but to the best of our knowledge, this is the first case of the CNS-HL associated with lymphatoid granulomatosis.

16.
Ann Agric Environ Med ; 27(1): 160-164, 2020 Mar 17.
Artículo en Inglés | MEDLINE | ID: mdl-32208597

RESUMEN

Richter's syndrome (RS) is a rare complication in which chronic lymphocytic leukaemia (CLL) or small lymphocytic lymphoma (SLL) transforms into a more aggressive type of lymphoma - diffuse large B cell lymphoma (DLBCL), or Hodgkin's lymphoma (HL). The review describes the clinical case of a patient with CLL and RS diagnosis. A computed tomography (CT) scan of the abdominal cavity detected numerous normodense areas in the liver. Simultaneously, ultrasound examination (USG) of the thyroid revealed the presence of a solid hypoechogenic lump. The material sampled from closed biopsies of liver and thyroid in both cases allowed the diagnosis of diffuse large B cell lymphoma (DLBCL). The liver and the thyroid are particularly rare locations of RS. However, those cases allowed the conclusion that RS may occur even in a very unexpected and less probable location.


Asunto(s)
Leucemia Linfocítica Crónica de Células B/diagnóstico , Neoplasias Hepáticas/patología , Linfoma de Células B Grandes Difuso/diagnóstico , Neoplasias de la Tiroides/patología , Femenino , Humanos , Leucemia Linfocítica Crónica de Células B/patología , Neoplasias Hepáticas/diagnóstico por imagen , Linfoma de Células B Grandes Difuso/patología , Persona de Mediana Edad , Neoplasias de la Tiroides/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Ultrasonografía
17.
Leukemia ; 34(9): 2354-2363, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32647324

RESUMEN

Chronic lymphocytic leukemia (CLL) is a disease of the elderly, characterized by immunodeficiency. Hence, patients with CLL might be considered more susceptible to severe complications from COVID-19. We undertook this retrospective international multicenter study to characterize the course of COVID-19 in patients with CLL and identify potential predictors of outcome. Of 190 patients with CLL and confirmed COVID-19 diagnosed between 28/03/2020 and 22/05/2020, 151 (79%) presented with severe COVID-19 (need of oxygen and/or intensive care admission). Severe COVID-19 was associated with more advanced age (≥65 years) (odds ratio 3.72 [95% CI 1.79-7.71]). Only 60 patients (39.7%) with severe COVID-19 were receiving or had recent (≤12 months) treatment for CLL at the time of COVID-19 versus 30/39 (76.9%) patients with mild disease. Hospitalization rate for severe COVID-19 was lower (p < 0.05) for patients on ibrutinib versus those on other regimens or off treatment. Of 151 patients with severe disease, 55 (36.4%) succumbed versus only 1/38 (2.6%) with mild disease; age and comorbidities did not impact on mortality. In CLL, (1) COVID-19 severity increases with age; (2) antileukemic treatment (particularly BTK inhibitors) appears to exert a protective effect; (3) age and comorbidities did not impact on mortality, alluding to a relevant role of CLL and immunodeficiency.


Asunto(s)
Betacoronavirus , Infecciones por Coronavirus/patología , Leucemia Linfocítica Crónica de Células B/complicaciones , Neumonía Viral/patología , Adenina/análogos & derivados , Factores de Edad , Anciano , Anciano de 80 o más Años , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , COVID-19 , Comorbilidad , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/mortalidad , Femenino , Humanos , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Pandemias , Piperidinas , Neumonía Viral/diagnóstico , Neumonía Viral/mortalidad , Pronóstico , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Pirazoles/farmacología , Pirazoles/uso terapéutico , Pirimidinas/farmacología , Pirimidinas/uso terapéutico , Estudios Retrospectivos , SARS-CoV-2 , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios
18.
Med Oncol ; 36(9): 79, 2019 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-31375939

RESUMEN

Chronic lymphocytic leukemia (CLL) is one of the most frequent lymphoproliferative diseases. CLL is characterized by unusual heterogeneity, which probably reflects its biological and genetic lack of homogeneity. Clonal chromosome aberrations belong to the most important prognostic and predictive factors in CLL. This research was aimed at observing clonal evolution in CLL at the chromosomal level, and assessing its clinical significance in relation to selected prognostic factors. The study involved 72 untreated patients with CLL. The preliminary investigations using cytogenetic banding analysis (CBA) and FISH were performed at the time of diagnosis, and again after about 24 months to observe clonal changes (clonal evolution). In addition, other parameters were evaluated, i.e., the expression of ZAP-70 kinase, CD38 antigen, and the mutation statuses of IGVH and NOTCH1 genes. Classic prognostic factors, i.e., categorized ZAP70 and CD38 expressions as well as mutations in IGVH and NOTCH1 genes did not influence the course of clonal evolution in the examined group of patients. Clonal evolution was detected in 45.8% of patients by means of CBA, and in 19.4% patients with FISH. Analysis of chromosomal aberrations in the examined group of patients showed that the incidence of 17p deletions and translocations in karyotypes has a negative impact on overall survival. CE was found to be a risk factor for the occurrence of disease progression (OR = 2.22). Our observations indicate that combined CBA and FISH are the most optimal techniques for monitoring clonal evolution in the course of CLL.


Asunto(s)
Evolución Clonal/genética , Leucemia Linfocítica Crónica de Células B/genética , Adulto , Anciano , Anciano de 80 o más Años , Aberraciones Cromosómicas , Bandeo Cromosómico , Progresión de la Enfermedad , Femenino , Humanos , Hibridación Fluorescente in Situ , Cariotipo , Leucemia Linfocítica Crónica de Células B/mortalidad , Leucemia Linfocítica Crónica de Células B/patología , Masculino , Persona de Mediana Edad , Pronóstico , Factores de Riesgo , Tasa de Supervivencia
19.
Ann Agric Environ Med ; 25(1): 56-59, 2018 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-29575875

RESUMEN

INTRODUCTION: Despite significant recent advances in the treatment of chronic lymphocytic leukaemia (CLL), most cases of the disease are still incurable. Treatment with monoclonal antibodies, such as ofatumumab, is one of the new therapeutic options. OBJECTIVE: Retrospective analysis of the efficacy of ofatumumab in patients with chronic lymphocytic leukaemia (CLL) treated in the Haematooncology and Bone Marrow Transplantation Department of the Medical University of Lublin, Poland, during 2011-2013. MATERIAL AND METHODS: The analysis included 5 patients (3 women and 2 men), aged 47-65, with Rai stage II-IV CLL, after a few lines of treatment. Three patients received ofatumumab in monotherapy and 2 patients received ofatumumab in combination with cyclophosphamide (50 mg/day) and dexamethasone (40 mg/day). All patients included in the study were diagnosed with an active form of leukaemia with symptoms such as lymphocytosis or massive lymphadenopathy. RESULTS: All patients responded to the treatment. Within the first 8 weeks of the treatment, levels of white blood cells returned to normal in patients with baseline lymphocytosis (3 patients). An increase in platelet levels was reported in 3 patients. Haemoglobin levels were higher or comparable to the baseline values in all studied patients after the completion of immunotherapy. In the patient with massive lymphadenopathy and hepato- and splenomegaly, the size of the lymph nodes, spleen and liver decreased and neutrophil levels increased. Time of progression was 5-12 months, and in one patient partial remission has been maintained. The treatment was well-tolerated in most cases. Asymptomatic neutropenia and an infection with Candida glabrata were observed. CONCLUSIONS: Ofatumumab may be a new and safe therapeutic option for patients with CLL after a few lines of treatment.


Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Antineoplásicos/uso terapéutico , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Centros Médicos Académicos , Anciano , Anticuerpos Monoclonales Humanizados , Recuento de Células Sanguíneas , Femenino , Humanos , Inmunoterapia , Leucemia Linfocítica Crónica de Células B/sangre , Leucemia Linfocítica Crónica de Células B/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Polonia , Estudios Retrospectivos , Resultado del Tratamiento
20.
Adv Clin Exp Med ; 27(12): 1683-1689, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30156387

RESUMEN

BACKGROUND: Richter's syndrome (RS) is a rare complication with an unfavorable prognosis, in which chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) transform into a more aggressive type of lymphoma, most commonly into diffuse large B cell lymphoma (DLBCL) or less often into Hodgkin's lymphoma (HL). OBJECTIVES: The objective of this research paper was to present a retrospective analysis of patients with CLL/SLL whose disease transformed into RS. MATERIAL AND METHODS: The study included 217 patients (100 women and 107 men) with CLL/SLL diagnosed in the years 2006-2015 at the Department of Hematooncology and Bone Marrow Transplantation of the Medical University of Lublin, which transformed into RS. We analyzed clinical, laboratory, immunophenotypic (ZAP-70 and CD38 expression), histopathological, and genetic data (del(17p), del(11q)), which was collected at the time of CLL/SLL diagnosis, and some which was collected at the time of transformation. RESULTS: Richter's syndrome was diagnosed in 4.6% of all CLL and SLL patients. The group of patients with RS consisted of 9 patients with primary CLL and 1 patient with a diagnosis of SLL (8 patients with transformation into DLBCL and 2 patients with transformation into HL). Leukemic lymphocytes showed evidence of peripheral blood lymphocyte membrane expression of ZAP70+/CD38+ (1 patient), of ZAP-70+/CD38- (3 patients), of ZAP-70-/CD38- (1 patient), and of ZAP-70-/CD38+ (5 patients). The deletion of 11q (del(11q)) was documented in 2 patients. In 4 cases, the location of RS was extremely rare (the thyroid gland, liver, skin, bladder, and central nervous system). CONCLUSIONS: Richter's syndrome is a rare, but probable complication of CLL/SLL with an unfavorable prognosis, and it should be taken into account at every stage of the disease, particularly when the course of the disease is aggressive.


Asunto(s)
Enfermedad de Hodgkin/diagnóstico , Enfermedad de Hodgkin/genética , Leucemia Linfocítica Crónica de Células B/diagnóstico , Leucemia Linfocítica Crónica de Células B/genética , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/genética , Proteína Tirosina Quinasa ZAP-70/genética , Adulto , Transformación Celular Neoplásica , Niño , Progresión de la Enfermedad , Femenino , Enfermedad de Hodgkin/patología , Humanos , Leucemia Linfocítica Crónica de Células B/patología , Linfoma de Células B Grandes Difuso/patología , Masculino , Pronóstico , Estudios Retrospectivos
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