Investigation of Mutations in Chronic Myeloid Leukemia and Assessment of the Relation between Mutations and the Clinical Response.

TEZ10344Tez (Uzmanlık) -- Çukurova Üniversitesi, Adana, 2013.Kaynakça (s. 40-51) var.viii, 53 s. : res. (bzs. rnk.), tablo ; 29 cm.AMAÇ: Kronik Myeloid Lösemi (KML) sık görülen ve önemli bir hematolojik hastalıktır. Tedavisinde son yıllarda yeni ilaçların kullanılmaya başlanması ile yüz güldürücü sonuçlar alınmaya başlanmış olsa da bazı hastalarda kullanılan yeni nesil ilaçlara karşı yanıtsızlık tespit edilmektedir. Bu hastalarda sekonder direncin en yaygın mekanizması BCR-ABL aktivasyonunun reaktivasyonudur. TKI tedavisine direnç sıklıkla BCR-ABL geninin ABL tirozin kinaz domainindeki nokta mutasyonlarıyla gelişir. Bu çalışmada amaç kliniğimizde KML tanısı ile takip ve tedavi edilen hastalarda mutasyon durumlarının incelenmesi ve verilen tedaviye olan yanıtın araştırılmasıdır. GEREÇ ve YÖNTEM: Araştırmamızda kliniğimizde takip edilen tüm KML hastaları - toplam 100 hasta – çalışmaya davet edilmiş, 6 hastaya ulaşılamadığından, 2 hasta da çalışmaya katılmak istemediklerinden çalışma dışı bırakılmış, geri kalan 92 hasta değerlendirilmiştir. Bu hastaların bilgilerine medikal kayıtlardan ve bire bir görüşmelerden ulaşılmıştır. Hastalarda en sık görülen mutasyonlardan beş tanesi - T315I, Y253H, E255K, E255V ve M351T mutasyonları - çalışıldı. Mutasyon varlığı ile hastalarda elde edilen majör moleküler yanıt arasındaki ilişki değerlendirildi. BULGULAR: İncelenen hasta grubunda mutasyon oranı % 3.3 olarak tespit edildi. Çalışmamızda mutasyonu olan 2 hastada T315I mutasyonu mevcut idi ve bu hastalarda nilotinib ve dasatinib tedavileri etkili olmadı. Bu hastalar halen akselere fazda idi. Yine diğer M351T mutasyonu olan hastada da bu ilaçlar ile majör moleküler yanıt elde edilemedi. SONUÇ: ABL kinaz domain mutasyonları arasında T315I mutasyon varlığı imatinib, dasatinib ve nilotinibe en yüksek direnci gösterir. T315I’ya ilave olarak F317 ve V299 dasatinibe ve Y253H, E255 ve F359 nilotinibe dirençlidir. Bu çalışmada da mutasyon mevcudiyetinin uygulanan tedavi ile elde edilen majör moleküler yanıt üzerine negatif etkili olabileceğini tespit ettik.AIM: Chronic Myeloid Leukemia (CML) is a common and important hematological disorder. Although recently good results have been obtained with the administration of new drugs, resistance to new generation drugs have been observed in some patients. In these patients the most common mechanism of secondary resistance is the reactivation of BCR-ABL activation. Resistance to TKI treatment often develops with the point mutations in the ABL tyrosine kinase domain of the BCR-ABL gene. The aim of the present study is to assess the mutation status of the patients with CML who have been treated and followed-up in our clinics and to assess the response to the treatments. MATERIALS and METHODS: All the patients with the diagnosis of CML treated in our clinics – totally 100 patients – were invited, 6 patients who could not be reached and 2 patients who did not want to participate were excluded and the remaining 92 patients were studied. The data of the patients were gathered from patient files and from the interview with the patients. The most common 5 mutations - T315I, Y253H, E255K, E255V and M351T mutations - were assessed. The association between the presence of mutations and rate of the major molecular response that had been obtained were analyzed. RESULTS: The prevalence of the mutations in the studied population was found to be %3.3. T315I mutation was detected in 2 patients and no response could be obtained with either nilotinib or dasatinib in these two patients. These patients were still in the accelerated phase. In one patient with M351T mutation major molecular response could not be obtained with these two drugs. CONCLUSION: Among ABL kinase domain mutations presence of T315I mutation is associated with the highest degree of resistance to imatinib, dasatinib and nilotinib. In addition to T315I, F317 and V299 mutations are resistant to dasatinib and Y253H, E255 ve F359 mutations are resistant to nilotinib. In this it was found that presence of mutations may affect the rate of major molecular response negatively

Can A Simple Complete Blood Count Predict Gestational Diabetes Mellitus?

Aim: To assess the role of simple complete blood count (CBC) in prediction of gestational diabetes (GDM). Materials and Methods: Pregnant women screened for GDM in 24-28 gestational weeks with a 75g-OGTT between January 2018-January 2020 were retrospectively investigated. Patients with a known systemic disease, using aspirin, low-molecular-weight heparin and steroids excluded. The assessed parameters in CBC were hemoglobin, hematocrit, red blood cells, mean corpuscular volume, mean corpuscular hemoglobin concentration, white blood cells (including neutrophils, lymphocytes, monocytes, eosinophils, basophils), platelets, platelet distribution width (PDW), mean platelet volume (MPV), red cell distribution width (RDW), nucleated red blood cell (NRBC), NRBC percentage, plateletcrit (PCT), platelet large cell ratio (P-LCR), immature granulocytes (IG) and IG percentage. Platelet mass index (PMI), neutrophil-to-platelet ratios (NPR) and lymphocyte-to-platelet ratios (LPR) were calculated. These parameters were compared between GDM patients and controls. Regression analysis was performed with the parameters that were significantly correlated with GDM. ROC curve analysis was done in order to find cut-off values. Results: RBC, WBC (all subtypes including immature granulocytes), platelet indices including PMI, NPR and LPR were all similar. Only RDW and NRBC were found to be significantly increased in GDM patients and came out to be independent predictors of GDM with maternal age and screening week. Conclusion: These findings suggest women with GDM may be accompanied with increased RDW and NRBC levels which seem to be independent predictors of this disease and these parameters may be used to monitor and evaluate the development of GDM

FIRST-TRIMESTER THYROID HORMONE REFERENCE DATA IN A TURKISH PREGNANT WOMEN POPULATION LIVING IN MIDDLE BLACKSEA REGION

WOS: 000336078100005Objective: No reference values for thyroid hormones have been established for Turkish pregnant women yet in the first trimester of pregnancy. The aim of the present study was to determine first trimester reference values for thyroid hormones in pregnant women living in middle Black Sea region of Turkey and getting service from our institution's laboratory. Material and Method: 1144 pregnant women admitted to Gaziosmanpasa University Faculty of Medicine hospital between January 2005 and January 2009 for first trimester visit were enrolled retrospectively. Maternal thyroid hormones measured as a part of laboratory examination were analyzed. Results: Anti-TPO and anti-TG antibodies were measured in 250 of the total 1144 women. 166 of these had antibody levels within the normal ranges. The 2.5th and 97.5th percentiles of these 166 antibody negative women were as follows: for TSH (mu IU/mL): 0.043-3.968, for fT4 (ng/dL): 0.840-1.638 and for fT3 (pg/mL): 2.059-4.386. The 2.5th and 97.5th percentiles of the remaining 894 antibody status unknown women were as follows: for TSH (mu IU/mL): 0.059-4.196, for fT4 (ng/dL): 0.634-1.527 and for fT3 (pg/mL): 2.340-4.143. Conclusion: For diagnosis of thyroid abnormalities; population, laboratory and even method based reference values should be established. This is a preliminary data from Turkish pregnant women

Isolated Tuberculous Epididymoorchitis Developing After Allogeneic Haematopoietic Stem Cell Transplantation: A Case Report

We report a case of isolated tuberculous epididymoorchitis developing in a patient after haematopoietic stem cell transplantation (HSCT). Forty-four-year-old male was admitted to the hospital with scrotal pain and swelling 6 months after an allogeneic HSCT using a fullymatched sibling donor because of his acute myeloid leukemia. There were scrotal tenderness, thickening and erythema on the right side. Brucella standard tube agglutination test was negative. Increased scrotal skin thickening, edema in the right epididymis and increased testicular vascularization were detected on ultrasonography. He was readmitted to our hospital with recurrent scrotal pain after 3 months of partial improvement with oral ciprofloxacin administered for a diagnosis of right epididymoorchitis. Pelvic magnetic resonance imaging revealed bilateral epididymoorchitis and scrotal abscess. Acid fast bacilli were detected on Ehrlich-Ziehl-Neelsen staining of the content of abscesses drained under local anesthesia. Mycobacterium tuberculosis complex was isolated on the 24th day of quadruple anti-tuberculosis therapy. Scrotal fistula developed on the first month of therapy which healed spontaneously after discontinuation of immunosuppressive agents. Full recovery was achieved after six months of antituberculosis therapy. As a result, tuberculous epididymoorchitis should be kept in mind in the presence of chronic epididymoorchitis developing in patients receiving immunosuppressive therapy

Does bone marrow evaluation have a contribution to clinical management in patients seventy five years and older?

Yaşlı hastalarda, özellikle de orta/ileri yaşlılık olarak tanımlanan ≥75 yaş grubunda kemik iliği değerlendirmenin klinik uygulamalardaki yeri net değildir. Bu çalışmada ≥75 yaşındaki hastalarda yapılan kemik iliği biyopsi ve aspirasyon endikasyonlarının, sonuçlarının ve yapılan kemik iliği incelemesinin klinik yaklaşıma ve sonuçlara katkısının değerlendirilmesi amaçlanmıştır. Ocak 2014- Aralık 2018 yılları arasında kliniğimizde kemik iliği incelemesi yapılan tüm ≥75 yaş hastalar retrospektif olarak değerlendirildi. Hastaların klinik özellikleri ve laboratuvar kan değerleri, periferik yayma, kemik iliği aspirasyon ve biyopsi sonuçları, aldıkları tedaviler ve sağ kalımları değerlendirildi. Çalışmaya dâhil edilen 81 hastanın ortalama yaşı 80,4±4 yıldı (75-95). İşleme bağlı komplikasyon görülmedi. Sitopeniler en sık endikasyondu. Anemi %87,6 oranında görülürken, lökopeni %25,9 ve trombositopeni %50,6 oranında görülmekteydi. En sık konulan tanı miyelodisplastik sendromdu (MDS). Yine multipl miyelom, miyeloproliferatif hastalıklar ve non-Hodgkin lenfoma MDS’yi takip ediyordu. Aspirasyon ve biyopsi yüksek oranda uyum göstermekteydiler. Genel olarak tedavi alan hastalarda ortanca sağ kalım süresi 69 ayken, almayan grupta 35 aydı. Yine 2 yıllık genel sağ kalım tedavi alan hastalarda %57 iken, almayan hastalarda %41,7 idi. Sonuç olarak ≥75 yaş hastalarda, ileri yaşa özgü hematolojik ve bazı non-hematolojik hastalıkların tanısının konulması için kemik iliği incelemesi güvenle yapılabilir. Kemik iliği incelemesinin endikasyonları çocuk ve genç erişkinlerinkinden farklıdır. Bu incelemeyle tanısı konulan hastalıklarda uygulanan tedaviler ile sağ kalım artmaktadır. Bu nedenle endikasyon varlığında, tanının konulması ve uygun tedavinin başlanması yolu ile sağ kalımı arttırmak için kemik iliği incelemesi bu yaş grubuna önerilmelidir.In clinical practice the role of bone marrow evaluation (BM) in the elderly, especially in patients over 75 years old who are referred as middle/advanced old, is not clear. In this study the aim was to assess the indications, results and the contribution of BM aspiration and biopsies to the clinical management and outcomes in patients over 75 years old. All ≥75 years old patients to whom BM evaluation was performed between January 2014 and December 2018 in our clinic were assessed retrospectively. The clinical properties, laboratory, peripheral blood smear and BM aspiration/biopsy results, the applied treatments and the survival outcomes were evaluated. The mean age of the 81 included patients was 80.4±4 (75-95). There was no procedure-related complication. Cytopenias were the most frequent indication. Anemia, leukopenia and thrombocytopenia were detected in 87.6%, 25.9% and 50.6% respectively. Myelodyspastic syndrome (MDS) was the most frequent diagnosis. Multiple myeloma, myeloproliferative diseases and non-Hodgkin lymphoma were the following diagnoses. Aspiration and biopsy showed high correlation. In general the median survival was 69 months in the treated patients and 35 months in non-treated patients. Twoyears overall survival was 57% in the treated and 41.7% in non-treated patients. In conclusion in order to diagnose hematological and some non-hematological disorders confined to advanced age, BM evaluation may be performed safely in patients over 75 years old. The indications of BM evaluation is different than childhood and younger adulthood. Treatment of disorders that were diagnosed with this procedure provides a survival benefit. For this reason whenever indicated, in order to diagnose and improve the survival with appropriate treatment, BM evaluation may be offered to patients in this age group

Düşük gradlı B hücreli lenfomalı bir hastada iki taraflı fasiyal paralizi ve rehabilitasyonu

Eş zamanlı iki taraflı fasiyal paralizi, nadir bir hastalıktır. İdiyopatik veya Lyme hastalığı, Guillain-Barre sendromu, sarkoidoz, viral enfeksiyonlar, sifiliz, pontin gliomlar ve lösemi gibi çeşitli hastalıklarla ilişkili olabilir. Altmış üç yaşında erkek hasta tam kan sayımında aşırı lökositoz ve yüzün sağ tarafında iki haftadır süren güçsüzlük ile hematoloji kliniğine başvurdu. Hastane yatışının yedinci gününde, yüzünün sol tarafında da güçsüzlük gelişti. Hasta iki taraflı fasiyal paralizi tanısı ile Fiziksel Tıp ve Rehabilitasyon kliniğine sevk edildi. Elektroterapi, el masajı ve egzersizden oluşan bir rehabilitasyon programına başlandı. Her iki taraftaki yüz kaslarına haftada üç seans galvanik akım uygulandı. Dört haftalık elektroterapi, günlük masaj ve egzersiz ile 12 seans sonunda, yüzün her iki tarafında da, duyu ve yüz kası kuvveti bakımından anlamlı iyileşme elde edildi. Takip sırasında 12. haftada ilave iyileşme kaydedildi. Bu yazıda, düşük gradlı B hücreli lenfomaya bağlı iki taraflı fasiyal paralizi olan son derece nadir bir olgu ve elektroterapi ve rehabilitasyon teknikleri ile elde edilen iyileşme sunulduSimultaneous bilateral facial paralysis is an uncommon condition. It may be idiopathic or associated with various disorders including Lyme disease, Guillain-Barre syndrome, sarcoidosis, viral infections, syphilis, pontine gliomas, and leukemia. A 63-year-old male was admitted to the Hematology clinic with a complete blood count showing excessive leukocytosis and a two-week history of right-sided complete facial weakness. On the seventh day of hospitalization, he also developed facial weakness on the left side. The patient with a diagnosis of bilateral peripheral facial paralysis was referred to the Physical Medicine and Rehabilitation department. He was started on a rehabilitation program including electrotherapy, manual massage, and exercise. Galvanic current was applied to the facial muscles of both sides as three sessions per week. After 12 sessions of electrotherapy, daily massage, and exercise for four weeks, a significant improvement was achieved on both sides in terms of sensation and facial muscle strength. Further improvement was noted at 12 weeks during follow-up. In this report, we present an extremely rare case of bilateral peripheral facial paralysis due to B-cell low grade lymphoma and the improvement with electrotherapy and rehabilitation technique