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Objectives: The main objective of the present study was to evaluate whether the use of plerixafor in combination with granulocyte colony-stimulating factor (G-CSF) or subsequent use of isolated G-CSF and then plerixafor following disease-specific chemotherapy, and whether it would allow for adequate peripheral stem cell collection in patients. Methods: The retrospective study evaluated 54 patients with previous mobilization failure who were administered plerixafor in 2 centers. In patients without any side effects, CD 34+ cell counts, the percentage of patients who were found eligible for autologous transplantation, the engraftment kinetics of the patients who underwent transplantation, and their overall survival results were compared between the two groups where G-CSF was used with plerixafor, or where plerixafor was used after isolated G-CSF following chemotherapy. Results: The median age of the patients was 49 years (range: 17-70), and 64.8% (n = 35) were males. It was identified that 31 (57.4%) patients underwent mobilization treatment with isolated G-CSF and plerixafor, and 23 (42.6%) patients underwent mobilization treatment with chemotherapy plus G-CSF and plerixafor. In all patients, mean hemoglobin level (11.3 ± 1.5 g/dL vs. 9.3 ± 1.3 g/dL; p < 0.001) and median platelet level (129.2 ×103/µL vs. 58.4 ×103/µL) were found to be higher, while febrile neutropenia rate (3.3% vs. 60.9%), the percentage of replacement patients (6.7% vs. 65.2%), and median days of G-CSF (6 vs. 9) were found to be lower on the day of plerixafor administration in the isolated G-CSF and plerixafor group compared to the chemotherapy and G-CSF and plerixafor group. Conclusions: In conclusion, our study demonstrated that administration of plerixafor is generally safe and well-tolerated. Regardless of the underlying disease, it offers an effective alternative for patients with previous failed mobilization attempts using conventional regimens, and allows stem cell collection with fewer apheresis sessions.

Objective: This study aims to examine the clinical and radiological features of skeletal changes in patients with thalassemia and provide a comprehensive overview of osteoporosis and osteoarthritis in these patients. Materials and Methods: We conducted a retrospective analysis of patients with transfusion-dependent thalassemia, both adults and children, who received follow-up care at our thalassemia center between 2019 and 2020.. Thalassemia was diagnosed via hemoglobin electrophoresis. Transfusion-dependent patients were defined as those who received transfusions every 2-4 weeks, while the control group consisted of individuals with thalassemia trait/carriers.. Both groups were analyzed for clinical characteristics, and Dual-energy X-ray absorptiometry (DEXA) scans, and radiographic images of the knee and wrist were evaluated. Results: DEXA scans of the femur and lumbar spine showed that the prevalence of osteoporosis , Synovial hypertrophy of the wrist joint , wrist effusion , knee effusion, and Power Doppler signals on wrist ultrasound scans was statistically significantly higher in transfusion-dependent thalassemia compared to patients with thalassemia carriers. Conclusion: Beta thalassemia is an inherited multisystem disease that leads to various musculoskeletal abnormalities. Knowledge of the musculoskeletal manifestations of thalassemia allows clinicians to guide their treatment. Familiarity with the radiological features of beta thalassemia is crucial for physicians in the timely diagnosis and management of thalassemia and its complications

Amaç: Sitomegalovirüs (CMV) reaktivasyonu allojenik hematopoetik kök hücre transplantasyo- nu sırasında sık görülür. Hepatit B reaktivasyonu (HBV), akut hepatit ve fulminan karaciğer yet- mezliği veya sadece HBV DNA düzeyinde artma şeklinde ortaya çıkabilir. Allojenik hematopoetik kök hücre nakli bağımsız bir risk faktörüyken, otolog hematopoetik kök hücre (HKH) alıcıları için risk ve nakil sürecine etkileri net bilinmemektedir. Çalışmamızda, geriye dönük olarak analiz etti- ğimiz otolog HKH alıcılarında CMV enfeksiyonu-engraftman ve hepatit B reaktivasyonu ilişkisini ortaya koymayı amaçladık. Hastalar ve Yöntem: Temmuz 2014-Aralık 2019 tarihleri arasında takip edilmiş olan toplamda 174 otolog KHN alıcı olan hasta değerlendirildi. CMV enfeksiyonuna bağlı organ tutulumları doku tanısı, görüntüleme ve klinik bulgularla doğrulandı. CMV enfeksiyonun tipi hastanın klinik izlemi, radyolojik raporları, hastanın tedavi alıp almamasına göre kopya sayısı seyri, virüsün herhangi bir dokunun patolojik incelemesinde tespit edilip edilmemesine göre değerlendirildi. Bulgular: Çalışmaya toplam 174 otolog KHN alıcı dahil edildi. CMV reaktivasyon oranı 18 has- tayla %10.3’tü. CMV reaktivasyonu olan olguların total Anti-HBc pozitif olma oranı, CMV negatif grubuna göre istatistiksel olarak anlamlı seviyede yüksek saptandı. CMV reaktivasyonu grubun- daki olguların HBV reaktivasyon oranı, CMV reaktivasyonu olmayan hasta grubundan istatistiksel olarak anlamlı seviyede yüksek saptandı. Sonuç: Otolog kök hücre nakli de viral reaktivasyonlar açısından dikkatli olunması gereken önemli bir tedavi tipini oluşturmaktadır. Objective: Cytomegalovirus (CMV) reactivation is a frequently encountered clinical condition during allogeneic hematopoietic stem cell transplantation. Hepatitis B reactivation (HBV) can occur asymptomatically only with re-emergence or increase in blood HBV-DNA levels, as well as in different clinical manifestations, including acute hepatitis and fulminant liver failure. While allogeneic hematopoietic stem cell transplantation is an independent risk factor, the risk for autologous hematopoietic stem cell (HSC) recipients and its effects on the transplantation process are not clear. In our study, we aimed to reveal the relationship between CMV reactivation and engraftment process and HBV reactivation in autologous HSC recipients. Patients and Methods: A total of 174 autologous HSC recipients who were followed-up between July 2014 and December 2019 were included in our study. Organ involvement due to CMV infection was confirmed by tissue pathology, imaging methods and clinical find- ings. The type of CMV infection was evaluated according to the patient’s clinical follow-up, radiological reports, the course of the copy number according to whether the patient received treatment, and whether the virus was detected in the pathological examination of any tissue. Results: The CMV reactivation rate was 10.3% with 18 patients. The rate of total Anti-HBc positivity in cases with CMV reactivation was found to be statistically significantly higher than in the CMV negative subgroup. The HBV reactivation rate of the patients in the CMV reactivation subgroup was found to be statistically significantly higher than the patient group without CMV reactivation. Conclusion: Autologous stem cell transplantation also constitutes an important type of treatment to be careful in terms of viral reacti- vation.

Plasmapheresis is a frequently used procedure that removes the pathogenic components from circulation. We aimed to evaluate the relationship between plasmapheresis, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and mortality in the intensive care unit (ICU) between 2014 and 2021.Forty-nine patients (27 females and 22 males) were included. Demographic characteristics, laboratory values of the day of admittance to the ICU, APACHE II scores, and length of stay were recorded.The mean age was 52.73 ± 16.93. APACHE II value (p = 0.003; p 0.01), NLR ratio (p = 0.001; p 0.01) and PLR ratio (p = 0.001; p 0.01) of the surviving group were lower than those of the deceased group, which was statistically significant.As high PLR and NLR levels suggest increased mortality in the ICU population, attention should be paid for increased NLR and PLR when plasmapheresis is decided on in the ICU.

Background & objective: Although the outcome of patients admitted to ICUs have considerably improved in recent years, hematopoietic stem cell transplantation (HSCT) continues to be significantly associated with mortality. We studied the prognostic factors associated with ICU mortality after HSCT. The Acute Physiological and Chronic Health Evaluation II (APACHE II) was used as a prognostic scoring system. Methods: Within the scope of the research, the clinical and laboratory data of 52 patients who were admitted to the ICU after undergoing HSCT between 2013 and 2019 were analyzed retrospectively. Results: Mortality risk was found to be 4.22 times higher in patients who received mechanical ventilation (MV) within the first 24 h (P = 0.047), 18.37 times higher in patients who received total parenteral nutrition (TPN) support (P = 0.007), and 158.17 times higher in recipients of vasopressor drug support compared to those who did not (P < 0.001). It was found that a one unit increase in GCS score decreased mortality risk by 0.58 fold (P = 0.015). Additionally, a one unit increase in heart rate was found to increase mortality risk by 1.03 fold (P = 0.010). Whereas, one unit increases in systolic blood pressure or diastolic blood pressure decreased the mortality risk by 0.91 and 0.92 fold, respectively (P = 0.001 and P = 0.002). Mortality was not associated with APACHE II or graft-versus-host disease. Conclusion: Receiving MV, TPN or vasopressor treatment, and having lower GCS, higher heart rate, lower systolic and diastolic blood pressure were associated with an increase in the risk of ICU mortality in HSCT recipients admitted to the ICU. Abbreviations: HSCT - hematopoietic stem cell transplantation; TPN - total parenteral nutrition; APACHE II - Acute Physiological and Chronic Health Evaluation II: GVHT - graft-versus-host disease; ICU - intensive care unit; GCS – Glasgow Coma Scale; MODS - Multiple organ dysfunction syndrome Key words: Hematopoietic stem cell transplantation; Intensive care; Mortality; Mechanical ventilation, parenteral nutrition; MV- mechanical ventilation; Citation: Tunay B, Sadri S. Evaluation of prognostic factors associated with intensive care unit mortality in patients with hematopoietic stem cell transplantation. Anaesth. pain intensive care 2022;26(4):480-487 ; DOI: 10.35975/apic.v26i4.1951 Received: Nov 12, 2021; Reviewed: May 11, 2022; Accepted: July 08, 2022

Aim: The aim of this study was to investigate the demographic characteristics of platelet apheresis donors during the coronavirus disease 2019 (COVID-19) pandemic, to examine the association of platelet counts with blood groups and body mass index (BMI), and to characterize the effects of BMI on platelet apheresis donation.Material and Methods: In this retrospective study, the demographic characteristics of platelet apheresis donors admitted to our center between January 2020 and January 2021 were examined, and hemogram parameters, previous platelet donation frequencies, and blood groups information were recorded. The relationship between donors' platelet counts, blood groups, and BMI were analyzed.Results: There was no statistically significant relationship between the platelet counts and blood groups. Although platelet counts were higher in Rh positive donors, no statistically significant relationship was found between platelet counts and the Rh group (p=0.675). Even though the platelet counts were lower in low-weight donors, there was no statistically significant relationship between platelet count and BMI groups (p=0.134). The lower collected platelet counts of the normal group, compared to the obese group, was found to be statistically significant (p=0.001). The number of donations for the overweight group being higher than the normal and obese groups was found to be statistically significant (p=0.002).Conclusion: Even though the platelet count increases with obesity, it does not have any statistical significance in healthy platelet donors. In conclusion, obesity does not have an inverse relationship with platelet apheresis donation and high BMI should not be considered as a prognostic factor for donation., Amaç: Bu çalışmanın amacı, koronavirüs hastalığı 2019 (coronavirus disease 2019, COVID-19) pandemi döneminde trombosit aferez donörlerinin demografik özelliklerinin araştırılması, trombosit sayılarının kan grupları ve vücut kitle indeksi (VKİ) ile ilişkisinin gözden geçirilmesi ve VKİ’nin trombosit aferez bağışı üzerindeki etkisini karakterize etmektir.Gereç ve Yöntemler: Bu geriye dönük çalışmada Ocak 2020 ve Ocak 2021 tarihleri arasında merkezimize başvuran trombosit aferez donörlerinin demografik özellikleri incelendi ve hemogram parametreleri, daha önceki trombosit bağış sıklığı ve kan grubu bilgileri kaydedildi. Bağışçıların trombosit sayıları, kan grupları ve VKİ arasındaki ilişki analiz edildi.Bulgular: Trombosit sayıları ile kan grupları arasında istatistiksel olarak anlamlı bir ilişki bulunmamıştır. Trombosit sayıları Rh pozitif bağışçılarda daha yüksek olmakla birlikte trombosit sayıları ile Rh grubu arasında istatistiksel olarak anlamlı bir ilişki bulunmamıştır (p=0,675). Düşük kilolu donörlerde trombosit sayıları daha düşük olsa da trombosit sayısı ile VKİ grupları arasında istatistiksel olarak anlamlı bir ilişki yoktu (p=0,134). Obez grup ile karşılaştırıldığında, normal kilolu gruptaki daha düşük trombosit torba sayısı istatiksel olarak anlamlı olarak bulundu (p=0,001). Normal kilolu ve obez gruplara göre daha fazla sayıda olan, fazla kilolu gruba yapılan bağış sayısı istatistiksel olarak anlamlı olduğu bulundu (p=0,002).Sonuç: Trombosit sayısı obezite ile birlikte artsa da bu durum sağlıklı trombosit donörlerde istatiksel olarak bir anlamlılığa sahip değildir. Sonuç olarak, obezitenin trombosit aferez bağışı ile ters bir ilişkisi yoktur ve yüksek VKİ bağış için prognostik bir faktör olarak kabul edilmemelidir.

Patients with solid malignancies are more vulnerable to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection than the healthy population. The outcome of SARS-CoV-2 infection in highly immunosuppressed populations, such as in patients with hematological malignancies, is a point of interest. We aimed to analyze the symptoms, complications, intensive care unit admissions, and mortality rates of patients with hematological malignancies infected with SARS-CoV-2 in Turkey.In this multicenter study, we included 340 adult and pediatric patients diagnosed with SARS-CoV-2 from March to November 2020. Diagnosis and status of primary disease, treatment schedules for hematological malignancies, time from last treatment, life expectancy related to the hematological disease, and comorbidities were recorded, together with data regarding symptoms, treatment, and outcome of SARS-CoV-2 infection.Forty four patients were asymptomatic at diagnosis of SARS-CoV- 2 infection. Among symptomatic patients, fever, cough, and dyspnea were observed in 62.6%, 48.8%, and 41.8%, respectively. Sixty-nine (20%) patients had mild SARS-CoV-2 disease, whereas moderate, severe, and critical disease was reported in 101 (29%), 71 (20%), and 55 (16%) patients, respectively. Of the entire cohort, 251 (73.8%) patients were hospitalized for SARS-CoV-2. Mortality related to SARS-CoV-2 infection was 26.5% in the entire cohort; this comprised 4.4% of those patients with mild disease, 12.4% of those with moderate disease, and 83% of those with severe or critical disease. Active hematological disease, lower life expectancy related to primary hematological disease, neutropenia at diagnosis of SARS-CoV-2, ICU admission, and first-line therapy used for coronavirus disease-2019 treatment were found to be related to higher mortality rates. Treatments with hydroxychloroquine alone or in combination with azithromycin were associated with a higher rate of mortality in comparison to favipiravir use.Patients with hematological malignancy infected with SARS-CoV-2 have an increased risk of severe disease and mortality.Solid malignite hastalarının şiddetli akut solunum yolu enfeksiyonu-koronavirüs-2 (SARS-CoV-2) enfeksiyonuna sağlıklı bireylerden daha yatkın oldukları gösterilmiştir. Bu verilerin ardından oldukça yoğun immünosupresif olan hematolojik malignite hastalarında SARS-CoV-2 infeksiyonu sonuçları ilgi konusu olmuştur. Biz de bu makalede Türkiye’de hematolojik malignite tanısı ile takip ve tedavi edilirken SARS-CoV-2 enfeksiyonu saptanan hastaların semptom, komplikasyon, yoğun bakım ünitesine yatış ve mortalite oranlarını değerlendirmeyi amaçladık.Çok merkezli çalışmamıza Mart-Kasım 2020 tarihleri arasında SARS-CoV-2 enfeksiyonu tanısı alan erişkin ve pediatrik 340 hastayı dahil ettik. Hastaların hematolojik malignite tanıları, hastalık statusları, tedavileri, son tedaviden enfeksiyona kadar geçen süre, komorbiditeleri, yaşam beklentileri değerlendirildi. Semptomları, oluşan komplikasyonlar ve sonuçlar analiz edildi.Kırk-dört hasta semptomsuz olarak enfeksiyonu geçirirken, semptomatik hastaların ateş, öksürük, ve dispne oranları sırasıyla %62,6, %48,8 ve %41,8 idi. Altmış altı hasta (%20) hastalığı hafif geçirirken, orta, ciddi ve kritik hastalık tanısı alanların oranı sırasıyla %29, %20 ve %16 idi. Tüm kohortta ölüm oranı %26,6 idi; ölüm hafif hastalığı olanlarda %4,4 , orta derece hastalık geçirenlerde %12 ve ciddi/kritik hastalık geçirenlerde ise %83 olarak saptandı. Aktif hematolojik hastalık olması, primer hematolojik hastalığa bağlı düşük hayat beklentisi, SARS-CoV-2 tanısı aldığında nötropenik olmak, yoğun bakıma alınmış olmak ve ilk sıra koronavirüs hastalığı-2019 tedavisi yüksek ölüm riski ile ilişkilendirilen faktörlerdendi. Tek başına veya azitromisin ile kombine olarak hidroksiklorokin kullanan hastaların sadece favipiravir kullananlara göre ölüm riskleri daha yüksek saptandı.SARS-CoV-2 infeksiyonu geçiren hematolojik malignite hastalarında daha yüksek oranda ciddi hastalık ve ölüm riski gözlenmektedir.

Introduction Immune checkpoint inhibitors are drugs that are included in the guidelines of hematological and solid cancer treatments, give highly effective results and increase T cell functionality. However, these drugs can cause immune-related adverse events resembling autoimmune diseases. Case report A 50-year-old male patient was admitted to an external center with complaints of chest pain and dyspnea. Thoracic CT revealed a 97 × 58 mm mass in the left lung, and a diagnosis of Small Cell Lung Cancer (SCLC) was made by biopsy. The PET/CT performed for staging was also evaluated as extensive stage small cell lung cancer. It was decided to give a combination of atezolizumab and carboplatin-etoposide to the patient. Management and outcome: The patient completed 3 cycles without any problem. Discordance was detected in the hemogram of the patient who came to the control for the assessment of response and had a regression in the imaging. Hemoglobin 9.6 g/dl (N: 14–17.5) hematocrit 14.8% (N: 41–51) were detected in the hemogram. Agglutinins were seen in the peripheral smear performed. Cold agglutinin (+4 positive) and indirect coombs (+3 positive) were found positive. Atezolizumab was stopped and methylprednisolone was started. After 10 days of treatment, discordance improved and methylprednisolone was discontinued by decreasing to half dose every 5 days. Discussion With the increasing use of immune checkpoint inhibitors, the variety of side effects has increased and case reports have increased. After detection of cold agglutinin, IgG, cryoglobulin, mycoplasma pneumonia, hepatitis B, hepatitis C and HIV were found negative in the differential diagnosis, Our case appears to be immune checkpoint inhibitor-related Cold Agglutinin Disease (CAD). It should not be forgotten that immune checkpoint inhibitors, which are widely used, may cause CAD, and hemoglobin-hematocrit discordance should be paid attention to in routine controls.

Background In the European LeukemiaNet (ELN) 2013 recommendations, chronic myeloid leukemia (CML) patients with warning response (WR) were suggested to be monitored closely continuing with the same tyrosine kinase inhibitor (TKI). Differently, the guidelines of the National Comprehensive Cancer Network considers switching to another TKI as an option. Patients and Methods We retrospectively evaluated 73 CML patients receiving first-line imatinib, who were followed and managed in accordance with ELN recommendations. We compared patients with molecular WR with patients with optimal response (OR) and failure regarding short- and long-term outcomes. Results The cumulative major molecular response (MMR) rates in patients with OR were significantly higher at any time point than those achieved by the WR group. Patients with WR at 3 months had significantly inferior failure-free survival (FFS) than optimal responders, but overall survival (OS) was similar. For 6 and 12 months, the WR and OR groups had similar FFS and OS. Twenty of 23 patients with WR at 12 months achieved MMR during imatinib treatment. Conclusion It takes longer to get to ELN time points with imatinib than second-generation TKIs (2GTKIs). Treatment might fail in a small proportion of the patients with WR during imatinib treatment, but close and careful monitoring and timely switching to 2GTKIs might translate into favorable outcomes. Avoiding early switch to 2GTKIs would prevent patients from experiencing potential toxicities. There is still a need for prospective comparative studies (ie, continuing imatinib treatment vs. switching to 2GTKIs) in patients with WR, to justify the validity of this response category and to explore the benefit of treatment change in these patients.

Objective The aim of the present study was to evaluate the efficacy and safety of eltrombopag, an oral thrombopoietin receptor agonist, in patients with chronic immune thrombocytopenia (ITP). Materials and Methods A total of 285 chronic ITP patients (187 women, 65.6%; 98 men, 34.4%) followed in 55 centers were enrolled in this retrospective cohort. Response to treatment was assessed according to platelet count (/mm3) and defined as complete (platelet count of >100,000/mm3), partial (30,000-100,000/mm3 or doubling of platelet count after treatment), or unresponsive (

Ar, Muhlis Cem/0000-0002-0332-9253 WOS:000474884600001 PubMed ID: 31282181 Increased number of patients with hemophilia have been identified to have osteoporosis at early ages. Low bone mineral density in the setting of hemophilia has been associated with decreased mobility, sedentary life style, on demand treatment or delayed prophylaxis, low body weight and viral infections. The aim of this study was to investigate the impact of hemophilia on bone health of adult patients living in a middle income country. A total of 61 adult patients with hemophilia who were followed at the Hematology Department of Cerrahpasa Medical Faculty, Istanbul University-Cerrahpasa were consecutively included in this study. Bone health of the patients was assessed using the bone mineral density (BMD) and vitamin D levels. Z and t scores are used for evaluation of BMD in patients with hemophilia aged < 50 and >= 50 years, respectively. Information on treatment and co-morbidities including viral diseases were obtained from the medical files of the recruited patients. Bone mineral density was found normal in 30, and low in 29 patients. Vitamin D levels were below 20 ng/ml in 46 patients. No significant relationship was found between the severity of hemophilia and bone density. Vitamin D levels were significantly lower in patients who had a history of joint intervention. Neither annual bleeding rate nor the treatment modality (on demand versus prophylaxis) were associated with the bone mineral density and vitamin D levels. Annual factor consumption was higher in patients whose bone mineral densities was low both in femoral and lumbar regions. The results of this study depicting the situation of adult hemophilia population from a middle income country show that bone mineral density and vitamin D levels were decreased in a considerable amount of patients at early ages.

Gemtuzumab Ozogamycin (GO) is a drug conjugated monoclonal antibody which targets CD33 an antigen highly expressed on the surface of AML blasts. GO is approved for the treatment of both newly-diagnosed and relapsed AML. Despite growing evidence regarding its efficacy and safety among AML patients there is limited data about the use of GO in isolated extra-medullary relapsed AML. Extramedullary AML remains as an unmet clinical need regarding the poor prognosis and lack of a standard therapeutic approach. Our cases demonstrated a rapid and long lasting response with a favorable toxicity profile, in patients who were treated with GO as a single agent after an isolated extramedullary relapsing disease. Our first case was a 40-years-old woman admitted to our outpatient clinic with pain in her joints and redness in her back and stomach. She was diagnosed with CD33-positive Acute Myeloid Leukemia according to the immunophenotyping of bone marrow blasts. Idarubicin and ARA-C (7+3) combination initiated as a frontline induction therapy and morphological remission was achieved after the first cycle of induction. After the first cycle of consolidation chemotherapy with high dose ARA-C she has relapsed with skin myeloid sarcomas and diffuse bone marrow infiltration. Soon after the relapsing disease she was put on to ida-flag salvage chemotherapy and she responded well with the disappearance of skin lesions and morphological complete remission of bone marrow. After achieving response, an allogeneic stem cell transplantation (HSCT) was applied from her sibling donor with a myeloablative conditioning. Unfortunately patient had a relapsing extramedullary disease with reappearance of skin lesions even with an ongoing acute skin gvhd (Figure) soon after allogeneic HSCT. Bone marrow biopsy revealed no increase in blast count. We have decided to initiate a novel targetted therapy to control the extramedullary disease. As her blasts infiltrating the skin were universally CD 33 positive we considered to put her on GO therapy with the approval obtained from health authority. GO was applied according to the dosage approved by FDA for relapsing disease. After the first cycle of GO she had a rapid disappearance of all skin lesions just complicated with a febrile neutropenic episode and re-activation of CMV infection which was controlled with Gancyclovir. She has retained a complete remission regarding extramedullary disease throughout the repeated courses of GO for 3 times, and she is still in remission for 4 months after the first appearance of skin lesions (Figure). Our second case was a 24-years-old boy who admitted to our outpatient clinic with a worsening fatigue and shortness of breath. He was also diagnosed with CD33-positive Acute Myeloid Leukemia according to the immunophenotyping of bone marrow blasts and was able to achieve a morphological CR after frontline induction therapy with 7+3 protocol. After two cycles of high dose ARA-C consolidation he was transplanted from a matched unrelated donor because of an intermediate cytogenetic risk profile. At the 14th month of allogeneic transplantation he had relapsed with a bone marrow blast count of 90% and harboring a monosomy on the 10th chromosome. After the first salvage chemotherapy with IDA-FLAG protocol he has achieved a morphological CR and we have decided to proceed with an alternative donor transplantation. But unfortunately soon after discharge, he has admitted to the emergency clinic with a new onset headache and nausea and vomiting. A cranial CT revealed multiple foci of solid masses with peripheral edema. We have performed a lumbar puncture and CSF fluid revealed a high number of CD33 positive blastic cells (over 100 cells per HPF). At the time of central nervous system (CNS) relapse his bone marrow was free of blastic infiltration. We decided to initiate GO treatment with the diagnosis of isolated central nervous system relapse of AML, accompanying intra-thecal chemotherapy via an Omaya Reservoir. He has received two cycles of GO which was complicated with neutropenic fever and grade 4 leukopenia and thrombocytopenia, and his CNS lesions also responded well and clinically he had no CNS related signs or symptoms. The patient received additional GO with continued response but unfortunately after a severe pneumonia he passed away at intensive care unit. Our case series documented a clinically relevant therapeutic field for GO in isolated extramedullary relapse of AML. Disclosures No relevant conflicts of interest to declare.

Background Thrombotic thrombocytopenic purpura is a potentially life-threatening condition. Although the introduction of therapeutic plasma exchange has reduced mortality rates from over 90% to 10%-20%, approximately 40% of patients relapse, and outcomes may be fatal in refractory patients. There is clearly a need for additional therapeutic approaches. Aims To describe the outcomes of relapsed/refractory thrombotic thrombocytopenic purpura patients treated with vincristine as an adjunct to therapeutic plasma exchange. Study design Cross-sectional study. Methods The medical records of all relapsed/refractory patients with thrombotic thrombocytopenic purpura treated with vincristine adjunct to therapeutic plasma exchange between October 2000 and December 2016 were retrospectively reviewed. Diagnosis of thrombotic thrombocytopenic purpura was based on clinical history, physical examination, and laboratory examinations. Patient demographics, laboratory findings, initial date and duration of therapeutic plasma exchange, dosage and time of administration of vincristine, and outcomes were recorded. Results The study included 15 patients [median age: 37 years (range: 26-65); 7 women and 8 men] with either relapsed or refractory thrombotic thrombocytopenic purpura who were treated with vincristine as an adjunct to therapeutic plasma exchange for a total of 22 episodes. Eighty-seven percent of patients achieved remissions in 20 of 22 episodes, with a median duration of remission of 29.5 months (range: 3-105). After a median follow-up of 55 months, 11 patients were alive. Vincristine was well tolerated with no safety concerns. Conclusion Vincristine offers a reasonable option for the treatment of patients with relapsed/refractory thrombotic thrombocytopenic purpura. Further studies evaluating vincristine in the front-line setting and in the relapsed/refractory setting are needed to validate the role of vincristine in thrombotic thrombocytopenic purpura patients.

Background The molecular response at 3 months of the original imatinib (OI) in patients with chronic myeloid leukemia has prognostic significance; however, this has never been tested for generic imatinib (GI). Patients and Methods We evaluated the BCR-ABL1 [international reporting scale ( IS )] transcript levels at 3 and 6 months to determine whether an early molecular response (EMR) had a prognostic effect on the outcome among chronic myeloid leukemia patients receiving GI. Ninety patients were divided into 2 groups, according to the imatinib they received, as OI (group A) and GI (group B). Results Two groups were equally balanced for age, gender, Sokal risk score, and optimal response. The 2 groups did not differ in achieving an EMR at 3 months, and patients with EMR at 3 months had significantly superior complete cytogenetic response and major molecular response rates compared with patients who did not achieve an EMR in both groups. The percentage of an optimal response [ BCR-ABL1 ( IS ), BCR-ABL1 ( IS ), 1%-10%] at 6 months was 93% and 95% for groups A and B, respectively ( P = .553). Patients with an optimal response (OR) at both 3 and 6 months had significantly superior event-free survival rates compared with patients without an OR in groups A and B. Conclusion The results of the present study have demonstrated most probably for the first time that an OR at 3 and 6 months in patients receiving either first-line GI and OI is clearly associated with greater response and event-free survival rates. Prospective randomized trials with larger numbers of patients and longer follow-up periods are needed to address the effect of EMR in patients receiving GI.

Dasatinib is one of the second-generation tyrosine kinase inhibitors used in imatinib resistance and/or intolerance, as well as in the frontline setting in patients with chronic myeloid leukemia-chronic phase, and also in patients with advanced disease. It is also utilized in Philadelphia chromosome-positive acute lymphocytic leukemia. While choosing the appropriate tyrosine kinase inhibitor (ie, dasatinib) for each individual patient, comorbidities and BCR-ABL1 kinase domain mutations should always be taken into consideration, among other things. This review mainly focuses on patient selection prior to dasatinib administration in the treatment of chronic myeloid leukemia.

Background: Although it may vary between different registries, the median age of chronic myeloid leukemia (CML) at diagnosis is between 50-60 years, and approximately 40% of the patients (pts) are diagnosed after age 60 [Hoffmann et al. Leukemia. 2015;29(6):1336-43]. Tyrosinekinase inhibitors (TKIs) have revolutionized the treatment of CML and currently pts with CML may expect to live close to normal lifespan. So the number of elderly CML pts with various potentialcomorbidities started to increase, which then brings out the issues regarding TKI toxicities, medication adherence and responses to TKI treatment. Aim: The aim of this study was to evaluate the efficacy and safety ofimatinib treatment in the elderly population (pts equal to or older than 60 years) with CML and to compare these data with younger pts (pts < 60 years). Patients and Methods: Pts diagnosed and followed in our clinic with CML were enrolled in the study. Patient demographics, dose and duration ofimatinib therapy, disease risk scores, cytogenetic and molecular responses,comorbidities, adverse events (AEs), follow-up durations and outcomes were evaluated from files of the pts, retrospectively. TheCharlsoncomorbidity index (CCI) of each patient was calculated as stated before [Breccia et al.Haematologica. 2011;96(10):1457-61]. Results: The patient cohort was consisted of 158 pts with a median age of 44 years (range, 18 - 83 years). Group A consisted of thirty-three pts who were equal to or older than 60 years (Fig. 1), and there were 125 pts (Group B) who were < 60 years of age (Table 1). The two groups were balanced regarding gender, disease stage, treatments prior to TKI therapy, and the starting dose ofimatinib. There were more pts with intermediate and highSokal risk scores in Group A than that of Group B (p Discussion: TKI therapy is relatively safe in elderly pts with CML, and cytogenetic and molecular responses are comparable with that observed in younger pts. In our institute, where pts are followed in a dedicated outpatient CML clinic, cytogenetic and molecular responses were similar in both elderly and younger pts leading to similar percentages of pts who were switched to 2GTKI therapy in both groups. Comorbidities can be problematic in elderly pts in whom CML and TKI relatedAEs are more common. However proper management of theseAEs including careful follow-up and timely TKI dose reductions may lead to successful outcomes. Inferior OS rates were observed in elderly pts with CML, but OS rates were similar in both groups when non-CML related deaths were excluded. Disclosures No relevant conflicts of interest to declare.

Background: Drug-induced pulmonary arterial hypertension (PAH) can be observed as an adverse event (AE) during the administration of dasatinib (DAS), which is a second generation tyrosine kinase inhibitor (TKI), used in the treatment of chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). The occurence of DAS-induced PAH at a late onset in most of the cases suggests a chronic pathological mechanism rather than an acute inflammatory or cardiac etiology. The treatment strategies of DAS-induced PAH include the cessation of the drug and PAH-specific therapies. Aim: The aim of the study was to evaluate the frequency, clinical features, management strategies and outcomes of patients with DAS-induced PAH among a cohort consisted of CML and Ph+ ALL patients who had received DAS as a salvage treatment after imatinib (IM) failure or intolerance. Patients and Methods: Forty patients with Ph+ leukemias who received second-line DAS were enrolled. Patients' demographics, Sokal risk scores, molecular and cytogenetic responses, comorbidities [including preexisting cardiac disease, renal insufficiency, hypertension and chronic obstructive pulmonary disease (COPD)], DAS dose, dosing intervals and treatment durations, durations of IM therapy prior to DAS, and if any, treatments prior to IM (interferon (IFN), cytarabine (Ara-C), and hydroxyurea (HU)) and follow-up periods were noted retrospectively. TKI response criteria were based on the recommendations of European LeukemiaNet, and the definitions of the CML phases and responses were as described elsewhere. Results: Twenty-four patients were male, and the median age was 45 years (range, 18-81 years). There were 39 patients with CML and one with Ph+ ALL. Among the thirty-nine CML patients, 3 were in accelerated phase (CML-AP), two with blast crisis (CML-BC), and the rest were in chronic phase (CML-CP). The percentanges of low, intermediate, and high Sokal risk scores were 46%, 33%, and 21%, respectively. Thirteen patients received only IM prior to DAS, whereas the others had used HU, IFN and Ara-C prior to IM. After a median duration of 41.5 months (range, 1-93 months) of IM, the reason for switching to DAS were IM failure and intolerance in 37 and 3 patients, respectively. DAS was administered with a median of 50 months (range, 2-78 months). During DAS treatment hematological AEs were observed in 6 patients, whereas in twenty-one pulmonary complications including exacerbation of COPD and pneumonia (n=1), pleuro/pericaridal effusions (n=19), PAH (n=5) and gastrointestinal bleeding (n=1) were detected. DAS therapy was ceased in 13 patients, of which ten were switched to nilotinib (NIL) due to AEs (n=7) and failure (n=3). Also, two patients received cytotoxic treatment due to BC and one had allogeneic hematopoietic stem cell transplantation (allo-HSCT). Five patients (12.5%) had DAS-induced PAH (Table 1). Four of them were in CML-CP at diagnosis, and one was in CML-AP. All cases received DAS due to IM failure. At the time of DAS initiation, 4 cases were in CML-CP and one in CML-BC. PAH was diagnosed by transthoracic echocardiography (TTE) in 3 patients, and by right heart catheterization (RHC) in 2, and it was observed after a median of 8 months (range, 2-25 months) of DAS. Three patients had accompanying pleuro/pericardial effusions. All patients with DAS-induced PAH were alive at the time of the analysis, and the management of PAH included dose reduction in two, and DAS was switched to NIL in 2 cases and allo-HSCT was performed in one. Conclusion: DAS-induced PAH seems to be reversible with the cessation and/or modification of DAS ± PAH-specific treatments. As pulmonary vascular toxicity related to DAS is thought to be molecule-related rather than class-related, it seems reasonable to switch to another TKI. The patients in our cohort had good responses to dose modification and drug cessation and none received PAH-specific therapy. Although DAS-induced PAH is mainly defined as a late complication, we detected that PAH can be observed even after 2 months of drug exposure. PAH can be observed during DAS treatment and physicians should be aware of this AE. Routine cardiopulmonary evaluation prior to and/or during DAS may be beneficial. Mechanisms under this pathological condition, preceding and prognostic factors, and treatment strategies are needed to be evaluated with prospective trials. Disclosures No relevant conflicts of interest to declare.

INTRODUCTION: Hematopoietic stem cell transplantation (HSCT) is an effective treatment for malignant and nonmalignant diseases. Improved long-term survival after HSCT translates into coming across secondary neoplasms. Contributory factors include primary disease, male sex, young age, prior therapies, conditioning regimens. The secondary neoplasms are particularly solid tumors, as well as lymphoproliferative disorders. Chronic graft-versus-host disease (GvHD) and immunosupressive therapy have also been reported to contribute to neoplasia risk. OBJECTIVE: The purpose of this study was to evaluate the frequency and distribution of the posttransplant secondary neoplasms in our center, to determine the possible contributory factors and relative effect of GvHD. METHODS: From 457 patients who received a HSCT between 1994-2014 clinical records of 312 patients were available to review retrospectively. 21 patients diagnosed with a secondary neoplasia in the posttransplant period are included in the study. Age, sex, primary diagnosis and treatment, time of HSCT, GvHD and immunosupressive treatments, localisation of neoplasms and outcomes were reported. RESULTS: Twenty-one cases of secondary neoplasms were observed (%6,7). The median age at diagnosis and transplantation were 44 and 47, respectively. The median follow-up time was 122 months (32-304). The most common primary diagnosis was Hodgkin's disease (HD). The most commonly used pretransplant conditioning regimen was BEAM. There were no cases of acute GvHD, chronic GvHD was observed in 3 cases. The most common secondary neoplasm was skin cancer followed by urogenital system cancers. The secondary malignancies seen in cases with chronic GvHD are concordant with GvHD sites. Three patients had benign neoplasms comprising fibroadenoma, mol hydatiforme and hibernoma; 2 patients developed preinvasive lesions of vulva (VIN 3) and oral cavity (squamous papilloma). For 20 patients the median time interval between the date of HSCT and diagnosis of a secondary neoplasia is 62 months (5-118); data is missing for 1 case. Two deaths were observed, 1 due to disease progression, 1 due to secondary colorectal malignancy. %90,4 of the study group are alive and in remission. Details are listed in Table 1 and 2. CONCLUSION: Patients undergoing HSCT have an increased risk of secondary cancers later in life. Known risk factors are primary disease, age at transplantation, pretransplant therapies, pretransplant conditioning regimens like total body irradiation, chronic GvHD and immunosuppressive therapies. Our study group is small to comment on these risk factors. Coherent with the literature skin cancer was the most common secondary cancer in our cohort as well. Interestingly we observed a trend towards increased urogenital cancers in comparison to reported data. This finding can be incidental because of the small number of study population or needs to be clarified yet. The increased risk of secondary neoplasms over time after transplantation and the greater risk among younger patients indicate the need for lifelong surveillance. Table 1 Characteristics of patients with secondary neoplasms after HSCT Characteristic n (%) Sex Female 10 (%47) Male 11 (%53) Primary diagnosis Acute myeloid leukemia 1 (%4,7) Acute lymphoblastic leukemia 3 (%14,3) Chronic myelogeneous leukemia 3 (%14,3) Multiple Myeloma 5 (%23,8) Hodgkin’s disease 6 (%28,6) Non-Hodgkin’s lymphoma 3 (%14,3) Prior therapy Chemotherapy 9 (%42,7) Chemoimmunotherapy 3 (%14,3) Chemoradiotherapy 5 (%23,7) Combination treatment* 3 (%14,3) Type of HSCT Allogeneic 5 (%23,8) Related 5 Unrelated 1 Autologous 15(%71,5) Both 1(%4,7) Conditioning regimens TBI+Cy 3 (%14,3) BEAM 8 (% 38,1) MEL 6 (% 28,6) BU+Cy 2 (% 9,5) Unknown 2 (%9,5) Acute GvHD 0 Chronic GvHD 3 (%14,3) Skin 3 Oral cavity 2 Eye 2 Pulmonary 1 Hepatic 1 Acute GvHD prophylaxis 7 (%33,3) CsA 1 MTX+CsA 6 Chronic GvHD treatment 3 (14,3) Steroid+CsA 2 CsA 1 Table 2 Characteristics and risk factors of patients who had secondary malignancy undergoing HSCT Breast Skin GIS Urogenital Lung Lymphoma Risk factors (n:2) (n:6) (n:2) (n:3) (n:2) (n:1) Prior therapy Chemotherapy 0 4 0 2 1 0 Chemoimmunotherapy 1 1 1 1 0 0 Chemoradiotherapy 1 0 0 0 1 1 Combination 0 1 1 0 0 0 Allogeneic Related 1 3 0 1 0 0 Unrelated 0 1 0 0 0 0 Autologous 1 3 2 2 2 1 TBI+Cy 0 1 0 0 0 0 BEAM 1 2 1 0 1 1 MEL 0 1 1 2 1 0 BU+Cy 0 1 0 1 0 0 Unknown 1 1 0 0 0 0 Chronic GvHD 0 2 0 0 0 0 Sex Female 2 2 2 1 0 0 Male 0 4 0 2 2 1 Disclosures No relevant conflicts of interest to declare.

Introduction: Recent studies indicate an increased risk for developing low bone mineral density (BMD) in patients with haemophilia. This has been suggested to result from less physical activity, and impaired vitamin D metabolism due to viral liver disease. Here we present the preliminary results of an ongoing study aiming to identify the risk factors for impaired bone health in adult haemophilia patients. Material and Method: Twenty-nine severe and 7 moderate haemophilia A and B patients were included in the study. Patient characteristics were given in Table-1. All patients had haemophilic arthropathy in ≥1 joints and were on prophylactic factor replacement therapy except 2 on demand patients. None of the patients had decompensated chronic liver disease. Eleven patients had a history of joint intervention (RAS or joint replacement). None of the patients had received on vitamin D supplementation. DEXA scans to screen BMD, blood chemical analysis including liver and kidney function tests, vit. D (25 hydroxy vitamin D) calcium, parathormone, alkaline phosphatase were obtained from all patients at study entry. Results: Osteoporosis and/or osteopenia according to WHO criteria were detected by DEXA scans in 2/3 of the patients. Twenty-six patients (72%) had vit. D levels below 20ng/mL, with half of them having levels less than 10ng/mL. Median lumbar and femur T scores were in the osteopenia range, being -1.2 and -2.2, respectively. Osteoporosis/penia rates and vit. D levels did not significantly differ between patients with severe and moderate haemophilia. However, patients with severe haemophilia had lower lumbar T scores (p=0.048) and seemed to acquire low BMD 2 times more likely than moderate haemophiliacs. Patients with a history of joint intervention had significantly lower vit. D levels (p=0.005) and 1.4 times more risk for low BMD. Conclusion: Preliminary results of our study are in line with the recent literature indicating an increased frequency for osteopenia and osteoporosis in patients with haemophilia. Despite their young age our cohort of patients had lower BMD and vitamin D levels than the age-matched healthy population. This is an interesting finding in a country like Turkey where the average yearly total number of hours of bright sunshine is over 3000. Data at hand suggest increased risk for reduced BMD especially in severe haemophiliacs with impaired joint mobility. The most probable underlying cause for reduced BMD seems to be haemophilic arthropathy related inactivity. Furthermore, impaired bone health seems to be partially associated with less sunlight exposure, which is probably a result of increased home confinement of patients with haemophilia due to joint disease. The study is still recruiting. We hope to clarify other questions regarding factors influencing bone health in haemophiliacs when the study is completed and additional data on radiological and physical examination as well as on quality of life are obtained. Table. Patient Characteristics (n=36) Age, years (median [range]) 35 [20 - 55] Type of haemophilia ( A/B), n 32/4 Genotype (severe/moderate), n 29/7 Factor activity level, % (median [range]) 0.4 [0.1 - 4.2] Type of treatment (prophylaxis/on demand) 34/2 Annual bleeding rate (median [range]) 4 [1 - 12] Joint replacement, number of patients (%) 7 (19) Radioactive synoviectomy, number of patients (%) 7 (19) Any joint intervention, number of patients (%) 11 (30.5) Lumbar T scores (median [range]) -1.2 [-5.2 - 1] Femur T scores (median [range]) -2.2 [-3.9 - 0.6] Vit. D, ng/mL (median [range]) 10.5 [1.3 - 45] Calcium, mg/dL (median [range]) 9.6 [8.9 - 10.2] Alkaline phosphatase, U/L (median [range]) 91.5 [53 - 177] Parathormon, pg/mL (median [range]) 39 [20 - 179] Haemoglobin, g/dL (median [range]) 14.75 [8.9 - 16] Osteopenia, number of patients (%) 12 (33) Osteoporosis, number of patients (%) 12 (33) HBV/HCV/HIV, n 1/11/0 Disclosures No relevant conflicts of interest to declare.