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Most commonly seen side effects with Tyrosine kinase inhibitors (TKI's) are hematologic toxicities. Besides, with dasatinib autoimmune side effects can be seen. Thrombotic thrombocytopenic purpura (TTP) is a life- threatening disease that can be related to various causes mainly autoimmune disorders or antineoplastic drugs. Few cases of TKI associated secondary thrombotic microangiopathies (TMA) have been reported in literature. Most of cases were diagnosed as hemolytic uremic syndrome (HUS) rather than TTP. Herein, we describe a 37-year-old CML patient who was diagnosed as immune-mediated TTP related to dasatinib.
Assuntos
Antineoplásicos/efeitos adversos , Dasatinibe/efeitos adversos , Púrpura Trombocitopênica Trombótica/induzido quimicamente , Adulto , Antineoplásicos/farmacologia , Dasatinibe/farmacologia , Humanos , MasculinoRESUMO
OBJECTIVE: Two-thirds of newly diagnosed patients with multiple myeloma (MM) are over 65 yr and/or physically unfit. Such patients are not eligible for high-dose chemotherapy or stem cell transplantation. The treatment aims in these patients should be to prolong survival by obtaining the best possible response, while maintaining good tolerability. The aim of our study was to evaluate the response to treatment and treatment-related toxicities in patients treated with conventional and novel protocols. METHODS: The records of 138 elderly (≥65 yr) patients with MM were retrospectively evaluated. RESULTS: The median overall survival(OS) of the patients was 46 months. The median progression-free survival (PFS) was 18 months. The OS and PFS of the patients treated with the conventional protocols did not differ significantly from those treated with the novel protocols. The statistical analysis of the quality of the response to the treatment with the conventional and novel therapies showed that complete remission (CR), combined with a very good partial response (VGPR), was significantly higher in the latter. However, the toxicities were higher in the novel treatment group. CONCLUSION: The novel drug protocols significantly increased the quality of the responses of elderly patients with MM to therapy, but they did not increase the patients' tolerability.
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Protocolos de Quimioterapia Combinada Antineoplásica , Mieloma Múltiplo/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Bortezomib/administração & dosagem , Dexametasona/administração & dosagem , Doxorrubicina/administração & dosagem , Monitoramento de Medicamentos , Feminino , Humanos , Masculino , Melfalan/administração & dosagem , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/patologia , Prednisolona/administração & dosagem , Indução de Remissão , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento , Vincristina/administração & dosagemRESUMO
Autologous stem cell transplantation (ASCT) is an established therapeutic modality in the treatment of lymphomas, especially in the relapse setting. In the present study, we aimed to define pretransplantation factors including Beta-2 microglobulin (ß2m) that influence outcomes following ASCT in patients with non-Hodgkin lymphoma (NHL). We analyzed retrospectively 78 NHL patients who had undergone ASCT from August 2010 to January 2013. The 2-year overall survival (OS) was 70% and the progression-free survival (PFS) was 60%. While remission status less than complete remission (CR) emerged to be a poor prognostic factor for OS in univariate analysis, high ß2m levels and comorbidity indices revealed to be independent poor risk factors for both OS and PFS. The present study demonstrated that even if the patient is in CR before ASCT if he has high ß2m, the 2-year OS decreases from 100% to 49%. Moreover, lymphopenia for the first time was demonstrated to predict PFS in ASCT in NHL patients. Our findings suggest that ß2m at transplantation predict the outcome after ASCT in NHL and further investigation with larger sample sizes is warranted.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Linfoma não Hodgkin , Microglobulina beta-2/sangue , Adulto , Idoso , Autoenxertos , Intervalo Livre de Doença , Feminino , Humanos , Linfoma não Hodgkin/sangue , Linfoma não Hodgkin/mortalidade , Linfoma não Hodgkin/terapia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Taxa de SobrevidaRESUMO
BACKGROUND: Conditioning regimens with high-dose chemotherapy and autologous stem cell transplantation (ASCT) are the mainstays of treatment in lymphoma patients. Although the most frequently used conditioning regimen is the BEAM regimen (Carmustine, Etoposide, Cytarabine, and Melphalan), and alternatives are also used in certain circumstances. The TEAM regimen (carmustine is substituted by the alkylating agent thiotepa) is one of these alternatives; however, data regarding the comparisons of efficacy and safety profiles of these 2 regimens is scarce. This study compared the outcomes of patients who received conditioning regimens with BEAM and TEAM and underwent an ASCT. METHODS: This study was conducted as a retrospective assessment of 294 patient outcomes in terms of efficacy and safety. Adult patients with lymphoma diagnosis who received BEAM or TEAM conditioning regimens and underwent an ASCT between January 1, 2016 and December 31, 2019 were included in the analyses. RESULTS: A total of 294 patients (median age at ASCT: 50 years, males: 60.5%, diffuse large B-cell lymphoma: 35%) were included. Eighty patients (27.2%) received the TEAM regimen, and 214 (72.8%) received the BEAM regimen. Regarding safety profiles, the thrombocyte engraftment time was significantly higher in the TEAM group (P = .003) and fever of unknown etiology was significantly higher in the BEAM group (P = .042). Also, nausea was more in the TEAM group (P = .031). The complete remission rate was 57.5% and 70.3% in the TEAM and BEAM regimens, respectively. The overall mortality rate was 37.3% and not significantly different between the groups (43% and 35% in the TEAM and BEAM groups, P = .22) over a similar median follow-up of 1667 days (P = .28). The 3-year survival rate was 66% and 67% and the 5-year survival rate was 52% and 58% in the TEAM and BEAM regimens, respectively, without significant difference. CONCLUSION: To the best of our knowledge, this is one of the few studies in the literature that compared the TEAM and BEAM as conditioning regimens for ASCT in lymphoma patients. The 2 regimens may provide similar overall survival outcomes and have a comparable safety profile. Although the BEAM regimen may be associated with longer progression-free survival times, the difference may be covered by the similar survival after ASCT.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Linfoma Difuso de Grandes Células B , Adulto , Masculino , Humanos , Pessoa de Meia-Idade , Carmustina/uso terapêutico , Etoposídeo/uso terapêutico , Estudos Retrospectivos , Transplante Autólogo , Recidiva Local de Neoplasia/tratamento farmacológico , Citarabina , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Melfalan , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Condicionamento Pré-Transplante , Transplante de Células-TroncoRESUMO
Background: Central nervous system (CNS) prophylactic options for diffuse large B-cell lymphoma (DLBCL) are administered differently in most centers. Unfortunately, there is still not a consensus on which patients, which regimen, for how many cycles, and when prophylaxis should be administered. Thus, this remains an unmet clinical need. Methods: We administered a survey study under the Lymphoma Scientific Subcommittee of the Turkish Society of Haematology. The questions were directed to hematologists through the monkey survey system. Results: The CNS International Prognostic Index score is a factor that clinicians frequently use when deciding on prophylaxis and is considered reliable. Although the perspective on anatomical risk factors is similar to that reported in the literature, breast involvement is still considered a critical risk factor in Turkey. Participants considered double or triple hit and double/triple expressor lymphoma as significant risk factors. Various methods have been used to demonstrate CNS relapses. Intrathecal prophylaxis is the preferred method. Conclusion: There are diverse methodological and technical ideas. The controversial results reported in the literature on the effectiveness of CNS prophylaxis may explain this finding. Although CNS prophylactic methods for patients with DLBCL are still controversial, the effect of secondary CNS involvement on survival is inevitable. Standard practices followed by national guidelines may be effective in reducing the variety of application methods and creating homogeneous results for efficacy and survival follow-up studies.
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Myelodysplastic syndrome (MDS) represents a heterogeneous group of potentially malignant diseases of bone-marrow stem cells. Acute myelogenous leukaemia (AML) is an inevitable outcome for many patients with MDS. Azacitidine has been reported to result in comparably higher response rates and improved survival than other treatment strategies. In this retrospective study, we report the results on 25 'real life' patients with MDS, CMML or AML treated with azacitidine between 2005 and 2009. All patients fulfilled the World Health Organization criteria for MDS and AML. No eligibility criteria other than diagnosis were considered. Complete response (CR) rate was observed in three of the 25 'real life' patients (12%) with a median duration of CR of 5 months (4-6 months). Seven patients (28%) had mono- or bi-lineage haematologic improvement and 15 patients (60%) showed neither morphologic nor haematologic response. Among 17 non-AML patients, the median time from onset of Aza-C treatment to AML transformation was 10 months (4-15 months). Overall death rate was 72%. All of the eight AML patients died. The death rate under Aza-C among non-AML patients was 59%. Unlike the results of the clinical trials, our data show that Aza-C has a limited activity in 'real-life' patients with MDS and AML. It is obvious that Aza-C can induce complete or partial responses in a considerable number of MDS patients but responses are usually not durable as we observed in our patients.
Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Azacitidina/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Síndromes Mielodisplásicas/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/mortalidade , Estudos RetrospectivosRESUMO
OBJECTIVE: Vascular events are a common complication in patients with polycythemia vera (PV) and essential thrombocythemia (ET). This study aimed to analyze the association between PAI-1 4G/5G and ACE I/D gene polymorphisms, and leukocytosis with thrombosis in patients with PV and ET. MATERIAL AND METHODS: In total, 64 patients with ET and PV were evaluated. Arterial or venous thrombosis, such as cerebral transient ischemic attack, ischemic stroke, myocardial infarction, peripheral arterial thrombosis, deep venous thrombosis, and pulmonary embolism, were defined as a vascular event. DNA samples were screened for mutations via reverse hybridization strip assay. RESULTS: In terms of PAI-1 gene polymorphism, the frequency of the 4G and 5G allele was 48.5% and 51.5%, respectively. The ACE allele frequency was 51.2% and 48.8% for D and I, respectively. There wasn't an association between occurrence of vascular events and the frequency of any allele. In terms of occurrence of vascular events, there weren't any significance differences between the patients that were carrying the ACE D/D homozygous allele to ACE I/D and those that carried the I/I allele (P = 0.93). There wasn't a significant difference in occurrence of vascular events between the PAI-1 5G/5G homozygote allele carriers, and the 4G/5G and 4G/4G allele carriers (P = 0.97). Vascular events were significantly more common in the patients with leukocytosis (leukocyte count >10 × 109 L-1) than in those without leukocytosis (leukocyte count ≤10 × 109 L-1) (P = 0.00). Age >60 years was also a significant risk factor for occurrence of vascular events(P = 0.008). CONCLUSION: PAI-1 and ACE gene polymorphisms were not considered new risk factors for thrombosis in PV and ET patients. On the other hand, leukocytosis at diagnosis was associated with the occurrence of vascular events in the patients with ET and PV.
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Only one-third of elderly (>60 years) AML and MDS-RAEB2 patients may receive intensive chemotherapy treatment alternatives that are limited in this patient group due to the potential of severe toxicity. Previous studies have shown that azacitidine and low dose cytarabine treatments may be a beneficial treatment option for these patients. In this study, we aimed to good results with low toxicity in elderly patients. We retrospectively analyzed the AML and MDS-RAEB2 patients who received azacitidine monotherapy and azacitidine and LDL-ara-c combination therapy for a comparison of their response to therapy, survival rates, and toxicity rates and for determining the factors that could affect their overall survival. A total of 27 patients who were diagnosed with de novo AML and MDS-RAEB2 and who received at least four cycles of chemotherapy were included in the study, and the data were evaluated retrospectively. When monotherapy and combination therapy groups were compared, the pretreatment bone marrow blast count was observed to be greater in the combination therapy group. A statistically significant difference was not detected between the groups regarding the response to therapy ratios (p = 0.161) (42.9 and 57.1 %, respectively). No difference was detected between the groups regarding therapy-related toxicity. Infections were the most common complication. Progression-free survival was 30.3 % for the azacitidine monotherapy group and 66.7 % for the combination (azacitidine + LD-ara-c) group. The factors influencing the overall survival rate were determined based on the response to the first-line therapies, more than a grade 2 infection, fever, and relapse in a multi-variance analysis. The combination therapy may be a well-tolerated treatment option for the elderly, vulnerable AML patients whose blast count is high in response to therapy rates, overall survival rates, and toxicities are not different, although the pre-treatment bone marrow blast count was greater in the combination therapy groups compared with the monotherapy group.
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Molecular balance between Angiopoietin-1 (Ang-1) and Angiopoietin-2 (Ang-2) has important effects in tumor angiogenesis. Ang-2 was shown to be elevated and proved to be a prognostic factor in acute myeloid leukemia (AML). To date studies revealed increased angiogenesis in bone marrows (BMs) of both myeloproliferative neoplasm (MPN) and AML patients. We conducted this study to demonstrate circulating levels of Ang-1 and Ang-2 in MPN patients since no data exists in literature. Thirty-three newly diagnosed MPN, 27 newly diagnosed AML patients and 25 controls (HC) were enrolled and Angiopoietin levels were determined with ELISA. We found that Ang-1 levels were higher whereas Ang-2 levels were lower in MPN and HC when compared to AML. Our results suggest that though angiogenesis is increased in both AML and MPN, angiopoietin serum level profile of the two diseases are different, and MPN patients have similar Ang-1 and Ang-2 levels as HC. We conclude that, according to our results Ang-1 and Ang-2 do not only regulate tumor angiogenesis and the difference between angiopoietin levels of acute and chronic myeloid neoplasms could be a reflection of other effects of these growth factors on tumor malignancy.
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Isolated breast relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is less often seen. Chronic graft-versus-host disease (cGVHD) is effective in preventing marrow relapse, but cGVHD seems not to be effective extramedullary relapse (EMR). We report the case of isolated breast relapse after first allo-HSCT for acute lymphoblastic leukemia (ALL). A 47-year-old female was diagnosed with ALL achieved complete remission with salvage chemotherapy and underwent allo-HSCT from an HLA-matched sibling male donor. At 17 months post-transplant, she presented with a bilateral breast masses that confirmed the diagnosis lymphoblast involvement. She had no evidence of leukemia in her marrow that determined 100 % full-donor chimerism when she was relapsed in her both breasts.
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Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a distinct and rare neoplastic entity and was classified as a subgroup of acute myeloblastic leukemia by the WHO in 2008. The median survival of patients was 15.2 months in a large case series. Allogeneic or autologous bone marrow transplantation has been recommended by some reports because of the disease's poor prognosis. We present three patients who presented with both skin and bone marrow infiltration. A 57-year-old man, a 62-year-old woman, a 64-year-old man were admitted to our outpatient clinic because of skin lesions. All of the patient's had bone marrow infiltration with positivity of the CD4, CD56, and CD123 staining. Survival of the patient's were 42, 6 and 12 months, respectively. Two of the patients who presented as blastic form didn't respond to any chemotherapy. BPDCN is a difficult disease to diagnosis and manage. CD4, CD56, CD123, CD303, and T cell leukemia/lymphoma 1. Cutaneous lesions can present as isolated nodules, macules, and disseminated macules and nodules. Positivities are crucial to the diagnosis of the disease in histological examination. Bone marrow infiltration or disease relapse at presentation were related to poor prognosis. Complete immunocytochemical staining must be performed for all patients who have cutaneous lesions with or without blood count abnormalities. Bone marrow (allogeneic or autologous) transplantation should be considered at the first remission.
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BACKGROUND: Changes occur in adhesion molecules in the disease course of multiple myeloma. P-selectin glycoprotein ligand-1 (PSGL-1, CD162) works as the ligand of selectin-neutrophil adhesion molecules. The aim of the present study was to investigate the relationship between PSGL-1 expression in the bone marrow and the known prognostic factors for multiple myeloma disease, disease stage, and survival. MATERIALS AND METHODS: This research included 63 patients with multiple myeloma (26 women [41.3%]; 37 men [58.7%]). The bone marrow biopsy samples obtained at disease diagnosis for each patient were stained immunohistochemically in terms of CD162 expression using standard diagnostic immunohistochemical staining methods. The laboratory results, CD162 expression, overall survival, demographic characteristics of the disease, and the relationship between CD162 expression and the disease stage were evaluated. RESULTS: Among the 63 patients included in the present study, the survival rate was 82.3% for 1 year, 73.2% for 2 years, 63.4% for 3 years, 51.7% for 4 years, 40.3% for 5 years, and 33.6% for 6 and 7 years. A statistically significant difference was not detected between the CD162 staining ratio and disease survival (P = .232). A statistically significant difference was not detected between the CD162 staining degree and survival rate (P = .184). However, the overall survival of the patients with no CD162 expression in the bone marrow was lower than that for the patients whose CD162 was stained 1, 2, and 3 degrees (12.33 ± 11.49, 28.65 ± 31.44, 37.25 ± 29.32, and 47.92 ± 45.29 months, respectively; P < .001). CONCLUSION: In the present study, CD162 staining and the staining degree, with the other standard immunohistochemical stains, were shown to be beneficial in the diagnosis of multiple myeloma disease. However, the results did not provide information about the disease course. Studies of a larger number of patients to examine P-selectin and interleukin-6 levels are needed to investigate the disease course.