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1.
Turk J Haematol ; 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38545671

RESUMO

Introduction: Primary immune thrombocytopenia (pITP) is an acquired autoimmune disorder related with increased destruction or/and impaired production of platelets. Diagnosis and management of ITP is challenging and require expertise and interpretation of international consensus reports and guidelines with national variations of availability. We aimed to assess the agreement of hematologists in Türkiye on certain aspects of both first line and second line management of patients with pITP. Methods: As a modified Delphi method, Turkish National ITP Working Group (14 steering committee members) founded under Turkish Society of Hematology (TSH) developed a 21-item questionnaire consisting of statements regarding diagnosis-first line and second line treatments of pITP and 107 adult Hematologists working either in university or state hospitals voted for their agreement or disagreement of the statements for two consequential rounds. Results: Participants have reached consensus on the use of corticosteroids as first line treatment and with limited duration. Methylprednisolone was the choice of corticosteroids rather than dexamethasone. Use of intravenous immunoglobulin was not preferred in patients without bleeding. It was also agreed that thrombopoietin receptor antagonists (TPO-RA) or rituximab should be recommended as second-line treatment, and that splenectomy could be considered 12-24 months after diagnosis in chronic pITP patients. Conclusion: The optimization of the dose and duration of cortTPO-RAs in addition to corticosteroids is necessary to improve the management of patients with pITP.

2.
Cardiovasc Toxicol ; 24(1): 41-48, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38108958

RESUMO

Cardiac magnetic resonance imaging is the gold standard to detect cardiac iron overload in patients with beta-thalassemia. The aim of this study was to evaluate cardiac iron overload using four-dimensional transthoracic echocardiography in thalassemia patients with and without cardiac involvement detected by T2* value and to compare the two techniques. This cross-sectional and observational study was conducted in 44 patients diagnosed with thalassemia major. Left ventricular systolic function was assessed using four-dimensional speckle tracking echocardiography-derived global longitudinal (GLS), circumferential, radial, and area strain indices. Left ventricular ejection fraction, volumes, and mass index were similar between the patients with T2* values less than 20 ms as compared to those with T2* values greater than 20 ms. However, patients with lower T2* values had significantly higher GLS values (- 17.0% vs. - 19.8%, p < 0.001) compared with those with higher T2* values. GLS demonstrated a sensitivity of 91.7% and a specificity of 71.9% at a cut-off value of - 18.5%; however, sensitivity was 75%, and the specificity was 84.4% at a cut-off value of - 17.5%. For - 18.5%, the positive predictive value was 55%, and the negative predictive value was 95.8%; for - 17.5%, these values were 64.2 and 90%, respectively. This novel echocardiographic method, tested for the first time in our study in comparison with cardiac MRI in an adult patient group, has been shown to predict cardiac iron overload in thalassemia patients in the subclinical period without LVEF decline. Four-dimensional GLS is a marker with high sensitivity and negative predictive value.


Assuntos
Sobrecarga de Ferro , Talassemia , Disfunção Ventricular Esquerda , Talassemia beta , Adulto , Humanos , Talassemia beta/complicações , Talassemia beta/diagnóstico por imagem , Volume Sistólico , Estudos Transversais , Função Ventricular Esquerda , Sobrecarga de Ferro/diagnóstico por imagem , Sobrecarga de Ferro/etiologia , Imageamento por Ressonância Magnética/métodos , Ecocardiografia Quadridimensional , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/etiologia
3.
Leuk Res ; 133: 107365, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37643508

RESUMO

Secondary immunodeficiency (SID) can occur as a result of multiple factors, including hematological malignancies, hematopoietic stem cell transplantation (HSCT), immunosuppressive treatment, biologics, and anti-inflammatory drugs. SID includes disorders resulting from impairment of both cellular and humoral immunity. This review focuses on the current risk factors, implications, and challenges in managing SID patients with impaired humoral immunity, which includes quantitative (hypogammaglobulinemia) and/or functional antibody and B-cell deficiencies specifically related to hematological malignancies and post-HSCT. Increased physician awareness is needed surrounding the disease presentation and early risk factors, as SID may be caused by several etiologies. Careful clinical assessment is then required to optimize management, which encompasses close monitoring of clinical parameters, vaccination, antibiotic prophylaxis, and immunoglobulin replacement therapy (IGRT). Novel methods of IGRT administration are associated with enhanced pharmacokinetics, IgG trough level stability, no need for venous access, as well as fewer systemic adverse events and better administration flexibility compared with traditional methods. Published international guidelines supported by observations from clinical data are broadly followed; however, best practices within each country have nuances that underline the need to tailor treatment plans to the individual patient.

4.
Turk J Med Sci ; 53(1): 352-359, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36945951

RESUMO

BACKGROUND: Since well-designed prospective comparative trials are lacking, haploidentical hematopoietic stem cell transplantations approach should be based on the expertise of a particular center. In this study, we aimed to report the results and outcomes of patients who underwent haploidentical hematopoietic stem cell transplantation. METHODS: : Thirty-nine patients who underwent transplantation in our clinic between 2015 and 2022 were retrospectively analyzed. Primary end point of this study is to find out the survival rates of the patients. RESULTS: The overall survival of patients was 29.9 ± 4.9 months. The disease-free survival of the patients was 37.8 ± 5.7 months. The 3-year overall survival rate of the patients was %50 and the 3-year disease-free survival rate of the patients was %53. Nineteen patients were nonsurvivors among a total of 39 patients. Busulfan-fludarabine-thiotepa was the most frequently used conditioning regimen for transplantation. Busulfan-fludarabin-antithymocyte globulin regimen is the second preferred conditioning regimen. Cyclosporine- cyclophosphamide-mycophenolate mofetil was the most widely used graft-versus-host disease prophylaxis regimen. Sixteen patients had graft-versus-host disease, 28% of the patients had acute graft-versus-host disease, and 13% had chronic graft-versus-host disease. Gastrointestinal system consists of the most involved organs in graft-versus-host disease since 15% of the patients had gastrointestinal graft-versus-host disease. First-degree relatives (parent/child) were the most frequent donor source for haploidentical hematopoietic stem cell transplantation. Sepsis was the most frequent reason of death among transplant patients. DISCUSSION: In our center, we prefer to use high dose posttransplantation cyclophosphamide after haploidentical hematopoietic stem cell transplantation for graft-versus-host disease prophylaxis. With this approach, our center's overall survival and disease-free survival rates are comparable and compatible with the literature findings.


Assuntos
Doença Enxerto-Hospedeiro , Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Criança , Humanos , Bussulfano/uso terapêutico , Estudos Retrospectivos , Estudos Prospectivos , Transplante de Células-Tronco Hematopoéticas/métodos , Ciclofosfamida/uso terapêutico , Ciclosporina/uso terapêutico , Doença Enxerto-Hospedeiro/prevenção & controle , Ácido Micofenólico/uso terapêutico , Neoplasias Hematológicas/terapia
5.
Turk J Med Sci ; 52(2): 413-419, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36161632

RESUMO

BACKGROUND: Thrombocytopenia is a common complication following hematopoietic stem cell transplantation (HSCT). Eltrombopag has been used in thrombocytopenia treatment after HSCT in recent years. Herein, we present our experience of 25 patients treated with eltrombopag for post-HSCT thrombocytopenia. METHODS: Fifteen autologous hematopoietic stem cell transplantation (AHSCT) and 10 allogenic hematopoietic stem cell transplantation (allo-HSCT) recipients treated with eltrombopag for treatment of prolonged isolated thrombocytopenia (PIT) or secondary failure of platelet recovery (SFPR) in the stem cell transplantation unit of Hacettepe University Hematology Department between 2017 and 2021 were included in the study. The primary endpoint of this study is eltrombopag response in patients diagnosed with PIT or SFPR. Platelet count above 50,000/mm3 for five consecutive days without platelet transfusion was considered as eltrombopag response. Overall survival (OS) analyses were calculated based on the time between HSCT and death from any cause. The patients who were alive at the last follow-up were censored at this time for calculation of OS analyses. RESULTS: AHSCT (66.7% (10/15)) and allo-HSCT (50% (5/10)) recipients responded to eltrombopag for the treatment of post-HSCT thrombocytopenia. There was no excess toxicity related to the eltrombopag use. The median response duration of allo-HSCT recipients and AHSCT recipients were 41 (13-104) days and 50 (7-342) days, respectively. There was a statistically significant OS duration difference between the responders and nonresponders in allo-HSCT and AHSCT recipients with p values of 0.005 and 0.02, respectively. DISCUSSION: Eltrombopag is promising for the treatment of thrombocytopenia after AHSCT and allo-HSCT in terms of efficacy and safety.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Trombocitopenia , Benzoatos/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Hidrazinas/uso terapêutico , Pirazóis , Estudos Retrospectivos , Trombocitopenia/tratamento farmacológico , Trombocitopenia/etiologia
6.
Turk J Haematol ; 39(3): 152-159, 2022 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-35445593

RESUMO

Objective: Studies comparing the efficacy and safety of prophylactic regimens for central nervous system (CNS) involvement in acute lymphoblastic leukemia (ALL) are scarce in adults. This multicenter retrospective study aimed to compare the efficacy of prophylactic regimens with and without CNS irradiation on the development of CNS relapse during follow-up. Materials and Methods: This was a multicenter comparative cohort study. A total of 203 patients were included from four tertiary care centers in Turkey. Patients were divided into two groups according to whether they received CNS irradiation or not. The groups were analyzed retrospectively regarding patient and disease characteristics, with the main focus being CNS relapse. Results: While 105 patients received chemotherapy-based prophylaxis, 98 patients received additional CNS irradiation. These groups were statistically comparable in terms of demographic characteristics and risk factors for CNS involvement. In the irradiation group, patients were younger and had more stem cell transplants. In a median of 23.8 (11.1-62.4) months, there was no difference between the two groups regarding CNS relapse-free survival (log-rank p=0.787). Conclusion: Craniospinal irradiation may not be indispensable for every adult patient with ALL, similarly to pediatric patients. It is crucial to avoid the long-term toxicities of radiation, especially in patients with long life expectancy. Craniospinal irradiation may be reserved for therapeutic use in cases of CNS relapse and prophylaxis for some high-risk patients.


Assuntos
Irradiação Craniana , Leucemia-Linfoma Linfoblástico de Células Precursoras , Doença Aguda , Adulto , Sistema Nervoso Central , Criança , Estudos de Coortes , Irradiação Craniana/efeitos adversos , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/radioterapia , Recidiva , Estudos Retrospectivos
7.
Artigo em Inglês | MEDLINE | ID: mdl-34603503

RESUMO

INTRODUCTION: The coronavirus disease 2019 (COVID-19), that is caused by severe acute respiratory syndrome corona virus 2 (SARS-CoV-2), has spread rapidly worldwide since December 2019. The SARS-CoV-2 virus has a great affinity for the angiotensin-converting enzyme-2 (ACE-2) receptor, which is an essential element of the renin-angiotensin system (RAS). This study is aimed at assessing the impact of the angiotensin-converting enzyme (ACE) gene insertion (I)/deletion (D) polymorphisms, on the susceptibility and clinical outcomes of the COVID-19 immunoinflammatory syndrome. Patients and Methods. A total of 112 patients diagnosed with COVID-19 between 1 and 15 May 2020 were enrolled in the study. ACE gene allele frequencies were compared to the previously reported Turkish population comprised of 300 people. RESULTS: The most common genotype in the patients and control group was DI with 53% and II with 42%, respectively. The difference in the presence of the D allele between the patient and control groups was statistically significant (67% vs. 42%, respectively, p < 0.0001). Severe pneumonia was observed more in patients with DI allele (31%) than DD (8%) and II (0%) (p = 0.021). The mortality rate, time to defervescence, and the hospitalization duration were not different between the genotype groups. CONCLUSION: Genotype DI of ACE I/D polymorphism is associated with the infectious rate particularly severe pneumonia in this study conducted in the Turkish population. Therefore, ACE D/I polymorphism could affect the clinical course of COVID-19.


Assuntos
COVID-19/genética , Peptidil Dipeptidase A/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Frequência do Gene , Estudos de Associação Genética , Humanos , Mutação INDEL , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Sistema Renina-Angiotensina , Adulto Jovem
8.
Turk J Haematol ; 38(4): 273-285, 2021 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-34448556

RESUMO

Objective: This study aimed to retrospectively evaluate the efficacy, safety, and survival outcome of single-agent ibrutinib therapy in chronic lymphocytic leukemia patients. Materials and Methods: A total of 136 patients (mean age ± standard deviation: 64.6±10.3 years, 66.9% males) who had received at least one dose of ibrutinib were included in this retrospective multicenter, noninterventional hospital-registry study conducted at 33 centers across Turkey. Data on patient demographics, baseline characteristics, laboratory findings, and leukemia-cell cytogenetics were retrieved. Treatment response, survival outcome including overall survival (OS) and progression-free survival (PFS), and safety data were analyzed. Results: Overall, 36.7% of patients were categorized as Eastern Cooperative Oncology Group (ECOG) class 2-3, while 44.9% were in Rai stage 4. Fluorescence in situ hybridization revealed the presence of del(17p) in 39.8% of the patients. Patients received a median of 2.0 (range: 0-7) lines of pre-ibrutinib therapy. Median duration of therapy was 8.8 months (range: 0.4-58.0 months). The 1-year PFS and OS rates were 82.2% and 84.6%, respectively, while median PFS time was 30.0 (standard error, 95% confidence interval: 5.1, 20.0-40.0) months and median OS time was 37.9 (3.2, 31.5-44.2) months. Treatment response (complete or partial response), PFS time, and OS time were better with 0-2 lines versus 3-7 lines of prior therapy (p<0.001, p=0.001, and p<0.001, respectively), with ECOG class 0-1 versus class 2-3 (p=0.006, p=0.011, and p=0.001, respectively), and with Rai stage 0-2 versus 3-4 (p=0.002, p=0.001, and p=0.002, respectively). No significant difference was noted in treatment response rates or survival outcome with respect to the presence of comorbidity, bulky disease, or del(17p). While 176 adverse events (AEs) were reported in 74 (54.4%) patients, 46 of those 176 AEs were grade 3-4, including pneumonia (n=12), neutropenia (n=11), anemia (n=5), thrombocytopenia (n=5), and fever (n=5). Conclusion: This real-life analysis confirms the favorable efficacy and safety profile of long-term ibrutinib treatment while emphasizing the potential adverse impacts of poorer ECOG performance status, heavy treatment prior to ibrutinib, and advanced Rai stage on patient compliance, treatment response, and survival outcomes.


Assuntos
Adenina/análogos & derivados , Leucemia Linfocítica Crônica de Células B , Piperidinas , Adenina/efeitos adversos , Idoso , Feminino , Humanos , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Piperidinas/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento , Turquia
9.
Turk J Med Sci ; 51(4): 1647-1652, 2021 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-33878857

RESUMO

Background/aim: The disease caused by SARS-CoV-2 was named as COVID-19. There is as yet insufficient information about the effects of HSCT on the clinical course of COVID-19. In the present study, we aimed to investigate the clinical course of COVID-19 in patients who had undergone HSCT. Materials and methods: We analyzed baseline characteristics, clinical course and findings of COVID-19, hospitalization and death rates, overall survival, and case fatality rates of HSCT recipients diagnosed with COVID-19 retrospectively. Results: 57.6% of the patients underwent AHSCT, and 42.4% underwent allo-HSCT. 60.6%, 27.3%, and 12.1% of the patients had mild, moderate, and severe COVID-19 or critical illness, respectively. Overall, 45.5% were hospitalized, 12.1% required intensive care, and 9.1% necessitated invasive mechanical ventilation. The total CFR was 9.1% in HSCT recipients, 22.2% in patients with active hematologic malignancy, and 4.2% in patients without active hematologic malignancy. Conclusion: It can be concluded that mortality of HSCT recipients is lower in patients whose primary disease is in remission compared to ones that are not in remission. Further studies with larger group patients are needed in order to delineate the effects of COVID-19 on HSCT patients.


Assuntos
COVID-19/mortalidade , COVID-19/fisiopatologia , Transplante de Células-Tronco Hematopoéticas/mortalidade , Hospitalização/estatística & dados numéricos , Transplantados/estatística & dados numéricos , Adulto , Idoso , COVID-19/terapia , Feminino , Transplante de Células-Tronco Hematopoéticas/estatística & dados numéricos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , SARS-CoV-2 , Índice de Gravidade de Doença , Turquia/epidemiologia
10.
Clin Lymphoma Myeloma Leuk ; 21(3): 147-153, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33451957

RESUMO

INTRODUCTION: Acute lymphoblastic leukemia (ALL) is a malign disease with poor prognosis in adults. After remission is achieved by induction therapy, administration of allogeneic hematopoietic stem-cell transplantation (AHSCT) is one of the standard treatment in adult ALL patients. Pediatric-inspired chemotherapy has been demonstrated to improve outcomes of adult ALL. The aim of this study was to compare the Berlin-Frankfurt-Münster-95 chemotherapy (BFM-95) regimen and AHSCT results in ALL patients with first complete remission. PATIENTS AND METHODS: Forty-seven patients who received the BFM-95 regimen and 83 patients who underwent AHSCT were compared. Primary endpoints were comparison of overall survival (OS) and disease-free survival (DFS) between groups. RESULTS: There was no significant difference between the groups in terms of age, gender, or performance status. In BFM-95 and AHSCT, relapsed disease occurred in 11 (23.4%) and 24 (28.9%), respectively; the respective values for treatment-related mortality were 6 (12.7%) and 10 (12%) (P = .32 and .91). Five-year DFS was 38% with BFM-95 and 57% with AHSCT (P = .014). There was no 5-year OS difference in both groups (64% vs 60%, P = .13). While leukocyte count < 30 × 109/L at the time of diagnosis (hazard ratio, 2.7; P = .021) and prophylaxis of central nervous system (hazard ratio, 2; P = .036) were prognostic for OS, the only factor that had a prognostic effect on DFS was AHSCT (hazard ratio, 1.6; P = .041). CONCLUSION: AHSCT currently offers no special OS advantage but increases DFS compared to the BFM-95 regimen. AHSCT may be considered at first complete remission in patients at low risk of transplant-related mortality.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adulto , Fatores Etários , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Causas de Morte , Criança , Terapia Combinada , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Prognóstico , Indução de Remissão , Transplante Homólogo , Resultado do Tratamento , Adulto Jovem
11.
Transfus Apher Sci ; 60(2): 103050, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33446450

RESUMO

OBJECTIVE: Aplastic anemia (AA) is a life-threatening disorder and may be associated with significant morbidity and mortality Currently, the first treatment option is allogeneic hematopoietic stem cell transplant (allo-HSCT) for patients younger than 40 years. Bone marrow is recommended as the stem cell source due to less graft versus host disease (GVHD) risk and better outcomes than peripheral blood (PB)-derived stem cell. The aim of this study is to share the data of AA patients who have underwent PB-derived allo-HSCT in our bone marrow transplantation center. METHODS: Twenty-seven patients who underwent PB-derived allo-HSCT from human leukocyte antigen matched sibling donors were analyzed retrospectively. RESULTS: The median follow-up time was 95.2 months (range, 4.8-235 months). The 10-year survival was 89 %. The median neutrophil and platelet engraftment time was 11 days (range, 9-16 days) and 13 days (range, 11-29 days), respectively. Primary platelet engraftment failure was observed in 1 patient (3.7 %). Acute and chronic GVHD observed in 2 (7.4 %) and 3 (11.1 %) patients, respectively. Neutropenic fever was observed in 13 (44.8 %) of patients until the engraftment after allo-HSCT. One patient died due to CMV infections, two died due to septic shock secondary to fungal infection. CONCLUSION: Although there is no prospective data directly comparing BM with PB as stem cell source in AA, observational studies indicates better OS with BM. PB can be used in certain situations such as higher risk for graft failure and donor preference. This study demonstrated that PB-derived stem cell seems to be a reasonable alternative to BM.


Assuntos
Anemia Aplástica/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco de Sangue Periférico/métodos , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
12.
Cardiovasc Toxicol ; 21(3): 216-223, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33068232

RESUMO

Tyrosine kinase inhibitors (TKIs) are established treatment for haematological malignancies. However, cardiac adverse effects, including the reduction in left ventricular ejection fraction and symptomatic heart failure remain clinical problems. The purpose of this study was to evaluate the left ventricular systolic functions in patients with chronic myeloid leukaemia receiving TKIs. A cross-sectional and observational study was conducted of 37 patients with chronic myeloid leukaemia receiving dasatinib or nilotinib after imatinib failure. Left ventricular systolic functions were evaluated using four-dimensional speckle tracking echocardiography derived global longitudinal (GLS), circumferential (GCS), radial (GRS), and area (GAS) strain indices. Mean ejection fraction, stroke volume, cardiac output and left ventricular mass index were similar between control and patient groups and within normal limits. GLS (- 16.7% vs - 20.8%, p < 0.001), GCS (- 13.0% vs - 15.6%, p = 0.002), and GAS (- 26.2% vs - 31.0, p < 0.001) values were significantly higher in the patient population than those of the controls. Dasatinib and nilotinib groups did not show differences regarding strain indices. In multivariate regression analysis, only the usage of dasatinib or nilotinib was found to be an independent risk factor for diminished GAS (ß = 4.406, p = 0.016), GLS (ß = 3.797, p = 0.001), and GCS (ß = 2.404, p = 0.040). Although imatinib, nilotinib, and dasatinib seem to be clinically safe in terms of cardiac function, monitoring of systolic functions using strain imaging, and long-term observation of patients may provide early detection of the possible cardiac toxicity.


Assuntos
Antineoplásicos/efeitos adversos , Ecocardiografia Quadridimensional , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Inibidores de Proteínas Quinases/efeitos adversos , Proteínas Tirosina Quinases/antagonistas & inibidores , Disfunção Ventricular Esquerda/diagnóstico por imagem , Função Ventricular Esquerda/efeitos dos fármacos , Adulto , Idoso , Cardiotoxicidade , Estudos Transversais , Dasatinibe/efeitos adversos , Diagnóstico Precoce , Feminino , Humanos , Mesilato de Imatinib/efeitos adversos , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/enzimologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Proteínas Tirosina Quinases/metabolismo , Pirimidinas/efeitos adversos , Estudos Retrospectivos , Medição de Risco , Sístole , Fatores de Tempo , Resultado do Tratamento , Disfunção Ventricular Esquerda/induzido quimicamente , Disfunção Ventricular Esquerda/fisiopatologia
13.
Turk J Haematol ; 38(1): 33-40, 2021 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-32539315

RESUMO

Objective: The prognosis of multiple myeloma (MM) patients is highly heterogeneous. The aim of this study is to determine the impact of patients' renal functions on the prognostic performance of the International Staging System (ISS). In addition, we aimed to evaluate the results of survival of patients with ISS stages and normal renal functions and those with ISS stages and abnormal renal functions with this study. Materials and Methods: Two hundred and four patients with newly diagnosed MM who received an autologous stem cell transplantation after induction chemotherapy in our tertiary care center between the years of 2001 and 2018 were evaluated. Results: There were 153 (75%) MM patients who had a glomerular filtration rate (GFR) of ≥60 mL/min and 51 (25%) MM patients who had GFR of <60 mL/min at the time of diagnosis in this study. There was a strong correlation between ISS stage and GFR. The ISS stages were higher in patients who had GFR of <60 mL/min than patients who had GFR of ≥60 mL/min (p<0.001). Patients with GFR of <60 mL/min were significantly more prevalent in the ISS III group than ISS I and II (p<0.001). Conclusion: This study showed that the ISS provides significant prognostic information in MM patients with GFR of ≥60 mL/min at diagnosis. However, in patients with impaired renal function at the time of diagnosis, B2-microglobulin may not be a good prognostic indicator since it may be affected by renal dysfunction as well as tumor burden.


Assuntos
Taxa de Filtração Glomerular , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/mortalidade , Estadiamento de Neoplasias , Adulto , Idoso , Biomarcadores , Tomada de Decisão Clínica , Gerenciamento Clínico , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/terapia , Estadiamento de Neoplasias/métodos , Estadiamento de Neoplasias/normas , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Análise de Sobrevida , Transplante Autólogo
14.
PLoS One ; 15(11): e0242497, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33237942

RESUMO

Despite the availability of various treatment protocols, response to therapy in patients with Acute Myeloid Leukemia (AML) remains largely unpredictable. Transcriptomic profiling studies have thus far revealed the presence of molecular subtypes of AML that are not accounted for by standard clinical parameters or by routinely used biomarkers. Such molecular subtypes of AML are predicted to vary in response to chemotherapy or targeted therapy. The Renin-Angiotensin System (RAS) is an important group of proteins that play a critical role in regulating blood pressure, vascular resistance and fluid/electrolyte balance. RAS pathway genes are also known to be present locally in tissues such as the bone marrow, where they play an important role in leukemic hematopoiesis. In this study, we asked if the RAS genes could be utilized to predict drug responses in patients with AML. We show that the combined in silico analysis of up to five RAS genes can reliably predict sensitivity to Doxorubicin as well as Etoposide in AML. The same genes could also predict sensitivity to Doxorubicin when tested in vitro. Additionally, gene set enrichment analysis revealed enrichment of TNF-alpha and type-I IFN response genes among sensitive, and TGF-beta and fibronectin related genes in resistant cancer cells. However, this does not seem to reflect an epithelial to mesenchymal transition per se. We also identified that RAS genes can stratify patients with AML into subtypes with distinct prognosis. Together, our results demonstrate that genes present in RAS are biomarkers for drug sensitivity and the prognostication of AML.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Leucemia Mieloide Aguda/tratamento farmacológico , Medicina de Precisão , Sistema Renina-Angiotensina/genética , Biomarcadores , Linhagem Celular Tumoral , Simulação por Computador , Citarabina/administração & dosagem , Citarabina/farmacologia , Conjuntos de Dados como Assunto , Doxorrubicina/administração & dosagem , Doxorrubicina/farmacologia , Etoposídeo/administração & dosagem , Etoposídeo/farmacologia , Ontologia Genética , Humanos , Concentração Inibidora 50 , Estimativa de Kaplan-Meier , Leucemia Mieloide Aguda/classificação , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Dinâmica não Linear , Prognóstico , Reação em Cadeia da Polimerase em Tempo Real , Tretinoína/administração & dosagem , Tretinoína/farmacologia
15.
Transfus Apher Sci ; 59(5): 102871, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32694044

RESUMO

Acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first identified in Wuhan, China; and spread all over the world. Reverse-transcription polymerase chain reaction (RT-PCR) test for SARS-CoV-2 usually returns to negative in 20 days post-infection, but prolonged positivity has been reported up to 63 days. A case whose viral shedding lasted 60 days is reported from China. Herein we report a patient with a history of autologous stem cell transplantation (ASCT) for lymphoma whose RT-PCR test remained positive for SARS-CoV-2 for 74 days. The prolonged RT-PCR positivity, despite convalescent plasma infusion, may suggest that the given antibodies may be ineffective in terms of viral clearance. In patients with hematological malignancies or immunosuppression, such as ASCT, may lead to prolonged viral shedding, and strict isolation is warranted for long-term SARS-CoV-2 infection control.


Assuntos
COVID-19/terapia , COVID-19/virologia , Linfoma/virologia , SARS-CoV-2/fisiologia , Eliminação de Partículas Virais/fisiologia , Humanos , Imunização Passiva , Masculino , Pessoa de Meia-Idade , Soroterapia para COVID-19
16.
Turk J Med Sci ; 50(8): 1851-1856, 2020 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-32512672

RESUMO

Background/aim: High-dose melphalan and autologous hematopoietic stem cell transplantation (AHSCT) is the standard treatment strategy for multiple myeloma (MM) patients who are eligible for it. The recommended dose of CD34+ hematopoietic progenitor cells (HPCs) for adequate engraftment is above 2 × 106/kg. The aim of this study was to evaluate the relationship between the dose of CD34+HPCs and survival in MM patients who underwent AHSCT at a tertiary care center. Materials and methods: Enrolled in this study were 271 MM patients who underwent AHSCT between 2003 and 2019. Clinical characteristics of the patients, disease status pre-AHSCT, reinfused CD34+ cell doses, and neutrophil and platelet engraftment days were recorded, retrospectively. The patients were divided into 2 groups according to whether the dose of reinfused CD 34+ HPCs was <5 × 106/kg or ≥5 × 106/kg. The groups were compared in terms of engraftment and overall survival (OS) times. Results: The median age of the patients was 54.8 (33­76) years. The median dose of infused CD34+ HPCs was 5.94 × 106/kg (1.47­59.5 × 106/kg). The median follow-up period was 54 months (4­211). The median OS of the patients was 103 months (11­144). The median neutrophil and platelet engraftment time was 10 (8­24) and 11 (7­40) days. Doses of <5 × 106/kg and ≥5 × 106/kg CD34+ HPC were reinfused in 38.1% and 61.9% of the patients, respectively. There was a negative significant correlation between the reinfused CD34+cell level and neutrophil/platelet engraftment times (r = ­0.32, P < 0.001; r = ­0.27, P < 0.001, respectively). The median OS times were observed as 103 months (11­144) and 145 months (123­166) for patients who had been administered <5 × 106/kg and ≥5 × 106/kg of CD34+ HPCs, respectively (P = 0.009). Conclusion: The increased amount of CD34+ autologous hematopoietic stem cell dose after high dose melphalan chemotherapy in MM patients shortened the platelet and neutrophil engraftment time and increased OS. Early platelet engraftment and administration of a CD34+ HPC count that is ≥5 × 106/kg can be considered as predictors of better survival in patients.


Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Sobrevivência de Enxerto/fisiologia , Transplante de Células-Tronco Hematopoéticas/métodos , Células-Tronco Hematopoéticas , Melfalan/uso terapêutico , Mieloma Múltiplo/terapia , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Transplante Autólogo
17.
Turk J Med Sci ; 50(4): 679-683, 2020 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-32496734

RESUMO

Background/aim: COVID-19 (Coronavirus disease of 2019) is an infectious disease outbreak later on declared as a pandemic, caused by the SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2). It spreads very rapidly and can result in severe acute respiratory failure. The clinical studies have shown that advanced age and chronic diseases increase the risk of infection. However, influence of the blood groups on COVID-19 infection and its outcome remains to be confirmed. The aim of this study is to investigate whether there exists a relationship between the blood groups of the patients and risk of SARS-CoV-2 infection and the clinical outcomes in COVID-19 patients Material and method: 186 patients with PCR confirmed diagnosis of COVID-19 were included in this study. Age, sex, blood groups, comorbidities, need for intubation and intensive care unit follow up and mortalities of the patients were analyzed retrospectively. 1881 healthy individuals, who presented to the Hacettepe University Blood Bank served as the controls. Results: The most frequently detected blood group was blood group A (57%) amongst the COVID-19 patients. This was followed by blood group O (24.8%). The blood group types did not affect the clinical outcomes. The blood group A was statistically significantly more frequent among those infected with COVID-19 compared to controls (57% vs. 38%, P < 0.001; OR: 2.1). On the other hand, the frequency of blood group O was significantly lower in the COVID-19 patients, compared to the control group (24.8% vs. 37.2%, P: 0.001; OR: 1.8). Conclusions: The results of the present study suggest that while the blood group A might have a role in increased susceptibility to the COVID-19 infection, the blood group O might be somewhat protective. However, once infected, blood group type does not seem to influence clinical outcome.


Assuntos
Sistema ABO de Grupos Sanguíneos , COVID-19/sangue , COVID-19/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/mortalidade , COVID-19/terapia , Estudos de Casos e Controles , Feminino , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Intubação Intratraqueal/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Prognóstico , Respiração Artificial/estatística & dados numéricos , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2 , Índice de Gravidade de Doença , Adulto Jovem
18.
Transfus Apher Sci ; 59(5): 102821, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32487513

RESUMO

During the ongoing COVID-19 pandemic due to the SARS-CoV-2 virus of which evidence-based medical paradigms cannot be easily applied; difficult clinical decisions shall be required particularly in the 'difficult-to-treat' cases of high risk group with associated comorbidities. Convalescent immune plasma therapy is a promising option as a sort of 'rescue' treatment in COVID-19 immune syndrome, where miraculous antiviral drugs are not available yet. In this report, we aim to convey our experience of multi-task treatment approach with convalescent immune plasma and anti-cytokine drug combination in a COVID-19 patient with extremely challenging comorbidities including active myeloid malignancy, disseminated tuberculosis and kidney failure.


Assuntos
COVID-19/complicações , COVID-19/terapia , Síndromes Mielodisplásicas/complicações , Síndromes Mielodisplásicas/virologia , Tuberculose/complicações , Tuberculose/virologia , Temperatura Corporal , COVID-19/diagnóstico por imagem , COVID-19/imunologia , Humanos , Imunização Passiva , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/diagnóstico por imagem , SARS-CoV-2/fisiologia , Tomografia Computadorizada por Raios X , Tuberculose/diagnóstico por imagem , Soroterapia para COVID-19
19.
Hematol Rep ; 12(1): 8267, 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32399162

RESUMO

The treatment landscape and clinical outcome of multiple myeloma (MM) patients have changed in the last decades, with an improved median survival of 8-10 years. This study aimed to evaluate the bortezomib, cyclophosphamide and dexamethasone (VCD) regimen versus bortezomib and dexamethasone (VD) regimen in patients with newly diagnosed MM. This study has been performed in a retrospective manner. One hundred and three patients with newly diagnosed MM who received chemotherapy at our tertiary care center between the years of 2009 and 2018 were evaluated. A total of 103 patients were included. The 5-year overall survival (OS) for patients who received VD regimen and patients who received VCD regimen were 75% and 83%, respectively. The OS for VD patients was 113.1±12.5 versus 122.2±9.5 months for VCD patients with no statistically significant difference (P=0.47). The 5- year PFS (progression free survival) for patients who received VD regimen and patients who received VCD regimen were 66% and 75%, respectively. The PFS for VCD patients was higher than the PFS for VD patients (67.1±7.4 versus 97.7±13.4 months), but no statistically significant difference was observed (P=0.59). Relapse rate (P=0.002) and mortality rate (P=0.01) were higher in VD group than VCD group and they were statistically significant. The OS and PFS were clinically longer in patients receiving VCD regimen than in patients receiving VD regimen, although not statistically significant. Cyclophosphamide should be given to patients at physician discretion and depending on patient's frailty function.

20.
Transfus Apher Sci ; 59(1): 102595, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31492570

RESUMO

BACKGROUND AND AIM: High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) has been considered the standard of treatment care for patients with multiple myeloma (MM). Insufficient mobilization and harvest of peripheral stem cells can be a major obstacle for performing ASCT. This is resulting in a lacking opportunity of cure in patients with MM. The aim of this study was to evaluate the factors which influence mobilization failure in patients with MM. MATERIALS AND METHODS: This study has been performed in a retrospective manner. Two hundred and thirty-four patients with diagnosed MM who underwent stem cell mobilization after induction chemotherapy at Hacettepe University Hospital between the years of 2003 and 2018 were evaluated. RESULTS: A total of 234 patients were included in this study. The median age was 54 (32-76) years at the time of diagnosis. In 209 of 234 patients (89.3%) first mobilization trial was successful. At univariate analysis, among parameters identifiable before mobilization, male gender (p = 0.03), number of chemotherapy cycle before stem cell mobilization (p < 0.001), second ASCT (p < 0.001) and immunomodulatory treatment before stem cell mobilization (p < 0.001) predicted mobilization failure. At multivariate analysis, number of chemotherapy cycle before stem cell mobilization (p = 0.03), second ASCT (p < 0.001) and immunomodulatory treatment before stem cell mobilization (p = 0.02) retained independent predictive power. CONCLUSION: Detectable different clinical characteristics of MM patients before initiating mobilization may be predictors of poor mobilization. Therefore, the mobilization protocol should be evaluated on a patient basis. Minimization of exposure to chemotheraputic agents in MM patients, especially immunomodulatory agents, may increase CD34+ cell harvest yields.


Assuntos
Mobilização de Células-Tronco Hematopoéticas/métodos , Mieloma Múltiplo/terapia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
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