Effects of tamoxifen on plasma tissue factor levels

Cancer patients have a high risk of thromboembolic disease. Although the increased levels of tissue factor (TF) in cancer patients have been reported in various studies, the effect of hormonal therapy i.e. tamoxifen on this manner has not been illuminated yet. In this pilot study, ten patients with localized breast cancer receiving adjuvant tamoxifen were studied for plasma tissue factor levels by the ELISA method, and test results were compared with the results of ten patients with localized breast cancer who not receiving adjuvant tamoxifen treatment. There was a slightly increase of plasma tissue factor levels in tamoxifen terated group compared with control group, but this increase was not statistically significant. Mean plasma TF level of the tamoxifen treated group was 63,87 pg/ml SEM23,63) (range 12,59 to 267,11) and of the control group was 42,83 pg/ml SEM7,56) (range 5,43 to 78,88).Nothrombotic complications were observed in both groups. According to these results, it is not possible to say that tamoxifen treatment can lead to the increase in plasma tissue factor levels and thereby hypercoagulability in patients with breast cancer. Further studies including more patients are needed to show the difference between two arms.Kanser hastaları tromboembolik olaylar açısından yüksek riske sahiptir. Kanserli hastalarda artmış doku faktörü düzeyleri rapor edilmesine rağmen tamoksifen gibi hormonal tedavilerin bu konudaki etkisi henüz netleştirilememiştir. Bu pilot çalışmada, adjuvan hormonal tedavi olarak tamoksifen alan erken evre meme kanserli 10 hastada prospektif olarak, ELISA yöntemiyle plazma doku faktörü düzeyleri ölçülmüş ve tamoksifen almayan erken evrememekanserli 10 hastanın plazma doku faktörü düzeyleri ile karşılaştırılmıştır. Kontrol grubu ile karşılaştırıldığında, tamoksifen ile tedavi edilen grupta plazma doku faktörü düzeylerinde hafif yükseklik gözlendi. Ancak bu yükseklik istatistiksel olarak anlamlı değildi (p=0.5). Tamoksifen ile tedavi edilen grupta ortalama plazma doku faktörü düzeyi 63,87 pg/ml ± SEM 23,63 (12,59- 267,11) iken kontrol grubunda 42,83 pg/ml ± SEM 7,56 ( 5,43-78,88) idi. Grupta hiçbir hastada trombotik komplikasyon gözlenmedi. Mevcut sonuçlarla tamoksifen alan erken evre meme kanserli hastalarda izlenebilen trombotik komplikasyonların gelişiminde doku faktörünün de rolü olabilir demek mümkün değildir, daha fazla hasta içeren çalışmalara ihtiyaç vardı

Assesment of patient's perspective on treatment free remission in CML: A Turkish multicenter cohort

Treatment free remission (TFR) is one of the main goals of therapy in Chronic Myeloid Leukemia (CML). Patient perspective and expectations have an indicative effect on discontinuation decisions. We analyzed 116 CML patients' perspective on TFR and factors that associated with willingness for tyrosine kinaz inhibitor (TKI) discontinuation from four different center in Turkey based on a national survey. Patients in our cohort had 7.8% awareness of TFR and after brief information willingness to attempt TFR has been reached to 58.9% in all population. Shorter disease duration was associated with enhanced willingness to attempt discontinuation in multivariate analyses (p=0.031). Most common patient related limitation for TKI discontinuation decision was anxiety about disease relaps and TKI resistance. Even disease relaps in TFR means molecular and detectable with close monitoring, patients still had considerable concerns about TKI discontinuation

Retrospective analysis of Turkish AML registry database, on behalf of AML working group of Turkish society of hematology

Abstract Introduction: To investigate the demographics and treatment details of the acute myeloid leukemia (AML) patients who were diagnosed and followed up in Turkey. Methods: Patients who were recorded on the database of Turkish AML Registry project were included in this study retro- spectively if they were diagnosed before 1st of Jan 2022. Demographics, patient, and disease related parameters both at the time of diagnosis and at the follow up and treatment outcomes were presented

Renal and Neurological Response with Eculizumab in a Patient with Transplant Associated Thrombotic Microangiopathy after Allogeneic Hematopoietic Progenitor Cell Transplantation

Transplantation-associated thrombotic microangiopathy (TA-TMA) is a challenge after allogeneic hematopoietic progenitor cell transplantation, considering the diagnostic uncertainties and lack of established treatment. We report a 43-year-old male patient who was diagnosed as TA-TMA after allogeneic progenitor cell transplantation for a progressive ALK negative anaplastic large cell lymphoma and responded to eculizumab with dramatically improving neurological status and renal function. Rapid neurological and renal recovery achieved after eculizumab could support a possible relationship between complement activation and TA-TMA. Eculizumab should be a reasonable treatment approach in patients with TA-TMA after allogeneic hematopoietic progenitor cell transplantation

Clinical outcomes and treatment patterns of primary central nervous system lymphoma: Multicenter retrospective analysis

Objectives: Primary central nervous system lymphoma (PCNSL) is a rare malignant disease with poor prognosis. Its low incidence leads to challenges in decision-making for treatment. As a matter of fact, there is still no consensus on the appropriate treatment modalities. In this context, the objective of this study is to investigate and comparatively assess the efficacies of several treatment modalities in the treatment of PCNSL. Methods: Thirty-four patients diagnosed with PCNSL at 5 different hematology centers between 2007 and 2021 were included in the study. Patients’ data from all five centers were collected retrospectively. Since ibrutinib is not approved for this indication in Turkey, consent for off-label use of ibrutinib is obtained from each patient. Ethics committee ap-proval was obtained on June 9, 2021 with decision number 2021/18-05. Results: The median age of the patients was 59 (min.: 22, max.: 78) years. The male-to-female ratio was 1.26/1. Nineteen (55.9%) patients had Eastern Cooperative Oncology Group (ECOG) performance score of ≥2. Fifteen (44.1%) patients had normal lactate dehydrogenase (LDH) levels and only 14.7% of the patients had B symptoms at the time of diagnosis. Magnetic resonance imaging (MRI) revealed a single mass lesion in 14 (41.2%) patients. As an induction therapy, meth-otrexate-based regimen was administered in 29 (85.3%) patients. Only 14 of the 34 patients received 4 or more cycles of high-dose methotrexate (MTX). About 32.4% of the patients received radiation therapy (RT) during follow-up as a part of induction therapy. Five patients received only RT due to poor performance status. Ibrutinib was administered in 5 patients for refractory disease. It was determined that four or more cycles of MTX treatment increased progression-free survival (PFS) (p=0.031) and overall survival (OS) (p=0.012). Moreover, RT improved PFS (p=0.023). Considering that the complete response achieved by induction therapy influences long-term survival, achievement of the best response to the treatment regimens administered in combination with new agents may prolong survival (PFS: p=0.01, OS: p=0.023). Conclusion: The findings of this study indicate that the initial response to treatment is crucial. Additionally, it was found that high-dose MTX treatment should be administered for 4 cycles or more in order to achieve the best results. Furthermore, it was determined that ibrutinib monotherapy was well-tolerated in our patients with relapsed/refractory disease, with excellent clinical benefits. In conclusion, a combination therapy consisting of high-dose MTX, ibrutinib, and rituximab appears to be a promising initial treatment approach in appropriate patients

Does Reinfusion of Stem Cell Products on Multiple Days Affect Engraftment?

Objective: High-doses of melphalan treatment with autologous stem cell transplantation in multiple myeloma (MM) remains a major treatment modality in suitable patients. A minimal dose of 2x106/kg CD34+ cells is preferred to achieve engraftment. Some patients need multiple leukapheresis procedures to achieve the necessary number of CD34+ cells, but this can cause a high volume of stem cell product that cannot be given in a single day. Whether or not the number of infusion days affects engraftment has not been studied before. We aimed to evaluate the impact of reinfusion of stem cells on multiple days on engraftment results. Materials and Methods: Demographic features, CD34+ cell doses, neutrophil and platelet engraftment days, hospitalization days, and number of infusion days of 149 autologous transplantations of 143 MM patients were evaluated retrospectively. Results: The data of 143 MM patients who were transplanted were analyzed retrospectively. Median age was 55±8.5 (range: 26-70) years with a male/female ratio of 91/58. Hospitalization days for all patients were 24±6 (range: 14-50) days. Mean CD34+ cell number was (7.5±5.3) x106/kg (range: 1.5-31x106/kg). CD34+ cells were reinfused in 1 day in 80.5% (n=120) of the patients, 2 days in 18.2% of the patients (n=27), and 3 days in 1.3% of the patients (n=2). For 29 patients, reinfusion was applied in more than 1 day because of the high volume of stem cell product. We did not see any dimethyl sulfoxide toxicity, cardiac arrhythmia, or volume overload complications. Hypertensive attacks during infusion were easily controlled by furosemide treatment. In the group with multiple infusions, the infused CD34+ cell numbers had a mean of (4.8±2.8)x106/kg, and in the single infusion group the mean was (8.1±5.5)x106/kg. There were no statistical differences between the two groups regarding platelet and neutrophil engraftment days (p=0.850, r=0.820 and p=0.500, r=0.440). There was no statistical difference between the two groups for hospitalization days (p=0.060, r=0.050). Conclusion: In cases with a high volume of stem cell product to acquire adequate stem cells, reinfusion can be safely applied across multiple days without any delay in engraftment

Prognostic significance of immunhistochemical classification of diffuse large B cell lymphoma

Diffüz Büyük B hücreli non-Hodgkin lenfoma (DBBHL), klinik davranısı ve histomorfolojik özellikleri açısından oldukça heterojendir. Bu nedenle hastalıgın seyrinin tahmin edilebilmesi ve buna uygun tedavi seçeneklerinin uygulanabilmesi için farklı prognostik faktörler arastırılmıs ve bu yolda pek çok çalısmalar yapılmıstır. Son çalısmalarda DBBHL, DNA mikroarrayı kullanılarak gen ekspresyon profillerine göre prognostik önemi olan alt gruplara ayrılmıstır. Ancak bu yöntemin pahalı ve her yerde uygulanamıyor olması nedeni ile mevcut alt grupların immünhistokimyasal boyama yöntemleri ile karsılıgının olup olmadıgı arastırılmıstır. Literatür ısıgında bu çalısmada da immünhistokimyasal olarak CD10, bcl-6, mum-1, bcl-2 boyanma paternlerine göre olguların prognostik alt gruplara sınıflandırılması ve bu sınıflamanın tüm sagkalım (TS), olaysız sagkalım (OS) üzerine olan etkilerinin incelenmesi amaçlandı. Ocak 1990 ile Mayıs 2005 tarihleri arasında DBBHL tanısı olan olgular retrospektif olarak taranarak, verileri yeterli olan ve patolojik kesitlerine ulasılabilen ardısık 50 olgu çalısmaya alındı. Kesitlerin CD10, bcl-6, mum1, bcl-2 boyanma paternlerine göre olgular, germinal merkez (GM) ve GM dısı (aktive B hücreli ve sınıflandırılamayan grup) olarak alt gruplara ayrıldı. %30'u GM, %70'i GM dısı B hücreli NHL olarak sınıflandırıldı. Erkek/Kadın oranı 29/21 olup, medyan yasları 55,5'ti. Hasta grubu çogunlukla uluslararası prognostik indeksi (IPI) düsük ve orta-düsük risk grubundan olusuyordu (41 olgu). IPI'nin TS ve OS üzerinde etkisi istatistiksel olarak anlamlıydı (p=0.0001, p=0.01). IPI'ye göre düsük ve orta-düsük risk grubunda yer alan olguların sagkalımları daha uzundu. Protein ekspresyonlarının TS üzerinde bireysel etkilerine bakıldıgında CD10 pozitif olgularda sagkalımın daha uzun, mum1 pozitif olgularda ise daha kısa oldugu, bcl-6 ve bcl-2'nin anlamlı etkisinin bulunmadıgı görüldü. Olgular sınıflandırıldıgında ise literatür ile uyumlu olarak TS ve OS'nin GM hücreli DBBHL'da anlamlı ölçüde uzun oldugu saptandı (p=0.002, p=0.04). Literatürde 5 yıllık sagkalım oranının GM olgularında %76, GM dısı olgularda %34 oldugu (p=0.001) ve bulguların cDNA mikroarray kullanılarak elde edilen sonuçlar ile benzer oldugu vurgulanmıstı. Bizim çalısmamızda da literatüre benzer olarak GM olgularında 5 yıllık sagkalım oranı %92, GM dısı olgularda %40 olup GM olgularının sagkalım oranı anlamlı ölçüde yüksekti (p=0.02). Sonuç olarak, DBBHL'da GM ve GM dısı seklindeki immünhistokimyasal sınıflama daha gerçekçi bir prognostik bilgi saglayabilir. IPI düsük risk grubunda dahi GM ve GM dısı olgular arasında sagkalım farkının olması, tedavilerin seçiminde prognostik sınıflamanın önemini vurgulamaktadır. Diffuse large B-cell Lymphoma (DLBCL) is heterogenous both clinically and morphologically. Because of this heterogenity, the different prognostic factors had been studied to be able to identify at diagnosis those patients who may benefit from more aggressive or experimental therapies. Currently, using a cDNA microarray, DLBCL can be divided into prognostically significant subgroups. Because this technology is expensive and not generally available, immunohistochemistry had been studied to subclassify DLBCL into prognostically significant groups. The aim of this study was to evaluate the use of immunoperoxidase staining for CD10, bcl-6, mum-1 and bcl-2 to subdivide DLBCL into prognostic subgroups and to examine the effect of this classification on overall survival rate (OS) and event free survival rate (EFS). Fifty consecutive patients with DLBCL diagnosed between January 1990 and May 2005 in our clinic were evaluated retrospectively. The M/F was 29/21 with the median age of 55,5 years. They were classified as germinal center B-cell-like (GCB) (30%), non- GCB (70%) [activated B-cell-like (ABC) (54%) and unclassified group (16%)] according to CD10, bcl-6, mum-1 and bcl-2 staining patern. The patient group mostly consisted of the patients with low and low-intermediate IPI (41 cases). IPI was found to be significantly predictive for OS and EFS (p=0.0001, p=0.01). The patients with low and low-intermediate IPI lived longer. When the protein expressions were studied individually, OS of the patients with CD10 positivity was found to be longer but OS of the patients with mum-1 positivity was found to be shorter. There were no significant effect of bcl-6 or bcl-2 on OS. The cases classified as GCB by immunohistochemistry had a significantly longer OS and EFS compatible with literature (p=0.002, p=0.04). In the literature, the 5-year OS for GCB group was 76%, compared with 34% for the non-GCB group (p=0.001) which was similar to that reported using the cDNA microarray. In our study, the 5-year OS for GCB group was 92%, compared with 40% for the non-GCB group (p=0.02). The existance of survival differences between GCB and non-GCB groups also in the patients with low IPI score showed the importance of prognostic classification in the riskadaptive treatment approaches. In conclusion, the classification as GCB and non-GCB phenotype based immunostains may enable to define more accurate prognostic groups in DLBCL

Current Approach to Diagnosis and Treatment of Agressive B - Cell Lymphomas

ÖZETPrekürsör B hücreli lenfoblastik lösemi (B-ALL) B lenfoid progenitörlerden orijin alır. WHO sınıflamasında ALL ve lenfoblastik lenfoma aynı hastalık olarak tanımlamıştır. Bu nedenle sıklıkla tedavi her iki grupta ortaktır. B-ALL yüksek heterojeniteye sahip pek çok genetik değişkenler ile karakterizedir. Pediyatrik ALL'lerde sağ kalım oranları %90'larda iken, erişkinlerde standart kemoterapiler ile sadece %40-50 civarlarında seyretmekte, artan yaş ile sonuçlar daha da kötüleşmektedir. Son yıllarda hastalığın patogenezi ve moleküler genetiği daha iyi anlaşılmış olup, pediyatrik protokollerin erişkinlerde kullanımı, risk hedefli tedavi algoritmaları, tirozin kinaz inhibitörleri, bispesifik antikorlar, antikor-ilaç konjugatları ve CAR-T gibi güncel tedaviler sayesinde umut verici sonuçlar elde edilmektedir. Aşağıdaki derlemede prekürsör B-lenfoblastik lösemide klinik özellikler ve güncel tedavi tartışılacaktır.Anahtar Kelimeler: Prekürsör hücreli lenfoblastik lösemi-lenfoma; tedaviABSTRACTPrecursor B-cell lymphoblastic leukemia (B-ALL) originates from B lymphoid progenitors. In the WHO classification, ALL and lymphoblastic lymphoma are defined as the same disease. Therefore, treatment is often common to both groups. B-ALL is characterized by many genetic variants with high heterogeneity. While the survival rate in pediatric ALL is 90%, it is only around 40-50% with standard chemotherapy in adults, and the results worsen with increasing age. In recent years, the pathogenesis and molecular genetics of the disease have been better understood, and promising results have been obtained with the use of pediatric protocols in adults, risk-oriented therapy algorithms, tyrosine kinase inhibitors, bispecific antibodies, antibody-drug conjugates and CAR-T. The following review will discuss the clinical features and current treatment in precursor B-lymphoblastic leukemia.Keywords: Precursor cell lymphoblastic leukemia-lymphoma; therapy</div

Kronik Miyeloid Lösemi ve Kronik Miyeloproliferatif Hastalıklar

ÖZET Primer Miyelofibrozis (PMF) klonal miyeloproliferasyon, atipik megakaryositik hiperplazi vekemik iliğinde fibroz ile karakterize bir miyeloproliferatif neoplazidir. Olguların yaklaşık %90’ı Januskinaz 2 (JAK2) geni (%50), kalretikülin geni (CALR) (%35) veya trombopoietin reseptör geninde(MPL) (%15) somatik mutasyona sahiptir. Standart bir tanı yöntemi olmayıp tanı için kemik iliği biyopsi yapılması sekonder nedenlerin dışlanması gereklidir. Prognoz için IPSS, DIPSS, DIPSS-plus gibiskorlama yöntemleri kullanılır. Tek küratif tedavisi allojenik kök hücre naklidir. Diğer tedaviler genellikle palyatiftir. Bu yazıda primer miyelofibroz tanı prognoz ve tedavisi güncel bilgiler ışığında sunulacaktır.Anah tar Ke li me ler: Birincil miyelofibroz; prognoz; tedaviABS TRACT Primary Myelofibrosis (PMF) is a myeloproliferative neoplasia characterized by clonalmyeloproliferation, atypical megamegakaryocytic hyperplasia and bone marrow fibrosis. Approximately 90% of the cases have a somatic mutation in the Janus Kinase 2 (JAK2) gene (50%), calreticulin gene (CALR) (35%) or thrombopoietin receptor gene (MPL) (15%). There is not a standartdiagnostic method but performing bone marrow biopsy and exclusion of secondary causes should bemade for the diagnosis. Scoring methods like IPSS, DIPSS, DIPSS-plus are used for prognosis. Theonly curative treatment is allogeneic stem cell transplantation. Other treatments are usually palliative.Here, the diagnosis, prognosis and treatment of PMF will be presented in the light of current information.Keywords: Primary myelofibrosis; prognosis; therapy</p

Langerhans Cell Sarcoma of the Axillary Lymph Node: A Case Report and Review of the Literature

Langerhans cell sarcoma is a rare, high-grade neoplasm with overtly malignant cytological features and the Langerhans phenotype. Herein, we present a rare case of Langerhans cell sarcoma in a 65-year-old female that presented with a painless enlarging mass in her right axillary region, along with the histopathological features and diagnostic characteristics in the light of literature on Langerhans cell sarcoma