Oral administration of ruxolitinib in psoriasis vulgaris: A case report of plaque psoriasis accompanied by myelofibrosis secondary to polisitemia vera successfully treated with oral ruxolitinib.

Psoriasis is a chronic inflammatory skin disease characterized by keratinocyte hyperproliferation and immune cell infiltration. Various therapies have been discovered for psoriasis, including topical treatments, phototherapy, conventional systemic agents such as methotrexate, retinoids and ciclosporine, as well as biologics. Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway inhibitors targeting Tumor Necrosis Factor alpha (TNF-α), interleukin (IL)-23 and IL-17 can be effective in psoriasis. Ruxolitinib is a US Food and Drug Administration-approved first-generation Janus kinase inhibitor for polycythemia vera, myelofibrosis, and acute graft-versus-host disease. Ruxolitinib cream has been investigated in various dermatologic diseases, including atopic dermatitis, vitiligo, psoriasis, and alopecia areata. However, there is limited data on the efficacy of oral ruxolitinib in patients with psoriasis vulgaris. Here, we report a patient diagnosed with myelofibrosis coexisting with psoriasis vulgaris, successfully treated with oral ruxolitinib.

The Prognostic Impact of Tumor Microenvironment and Checkpoint Blockade-Associated Molecules (PD-1, PD-L1, CD163 and CD14) in Nodal Diffuse Large B-cell Lymphoma, NOS.

It is aimed to determine expression of programmed cell death-1 (PD-1), programmed cell death ligand-1 (PD-L1), CD163 and CD14 in diffuse large B-cell lymphomas (DLBCL), and whether these markers may predict prognosis in DLBCL cases. A total of 52 nodal DLBCL, NOS cases with no known extranodal involvement at the time of diagnosis were evaluated. PD-1, PD-L1, CD163, and CD14 were studied by immunohistochemistry. The relationships between the results and clinical and laboratory prognostic markers were investigated. It was observed that patients with PD-1 expression < 5 positive cells/HPF had worse overall survival. No significant relationship was found between survival and PD-L1, CD163 and CD14 expressions. In addition, cases that are > 60 years of age, that have Eastern Cooperative Oncology Group (ECOG) performance score ≥ 2, stage IV disease, high International Prognostic Index score score (≥ 3), elevation of LDH, low albumin level, low hemoglobin level, low peripheral blood lymphocyte count, high peripheral blood neutrophil/lymphocyte ratio, high peripheral blood platelet/lymphocyte ratio were found to have worse overall survival. It was concluded that in patients with low number of PD-1 positive tumor-infiltrating lymphocytes have low survival rates and therefore PD-1 expression may be useful in indicating prognosis.

International Forum: The Turkish perspective on apheresis activity: The Turkish apheresis registry report.

Therapeutic apheresis is an extracorporeal treatment that selectively removes abnormal cells or harmful substances in the blood that are associated with or cause certain diseases. During the last decades the application of therapeutic apheresis has expanded to a broad spectrum of hematological and non-hematological diseases due to various studies on the clinical efficacy of this procedure. In this context there are more than 30 centers performing therapeutic apheresis and registered in the apheresis database in Turkey. Herein, we, The Turkish Apheresis Registry, aimed to analyze some key articles published so far from Turkey regarding the use of apheresis for various indications.

Acquired Hemophilia A In Adults: A Multicenter Study from Turkey.

Acquired hemophilia A (AHA) is a rare disease caused by autoantibodies inhibiting factor VIII (FVIII) activity. Although the conditionis usually idiopathic, there may be other underlying diseases. Treatment consists of two steps: treatment of acute bleeding and immunosuppression. In this multicenter study, we aimed to demonstrate the clinical characteristics, management details, and survival of AHA patients in Turkey. Data was collected from eleven centers in Turkey. aPTT, FVIII, FVIII inhibitor, and hemoglobin (HB) levels, mixing test results, and demographics at diagnosis, treatment information, adverse events, bleeding episodes during follow-up, relapses, and outcome were analyzed. Twenty-nine patients were analyzed (58.6% female). No underlying disorder could be detected in 14 patients. The most prevalent etiologies were pregnancy, malignancy and infections. The median FVIII activity and FVIII inhibitor titer at diagnosis were 0.7% (0.0-29.4%) and 32.6 BU (0.6-135.6 BU) respectively. Bleeding was severe in 44.8% of patients. The HB value was significantly lower in patients with severe bleeding. Most of the patients (n = 25, 86.2%) had only one bleeding episode without relapse, three patients (10.3%) had two bleeding episodes, and one patient had more than three bleedings. 21 (75%) patients received hemostatic therapy. The use of recombinant FVIIa was slightly higher than activated prothrombin complex concentrate (15 versus 10 patients). Immunosuppressive treatment was initiated in 26 (93%) patients. Regimens containing steroid, cyclophosphamide, and rituximab in different combinations were the most preferred. The median follow-up period was 13 months (2-156 months). Median overall survival was 154.97 months. Four and six-year survival were 90.9 ± 0.8% and 77.9 ± 14.1% respectively. This is a unique study that investigated the demographic characteristics, treatment approaches, and patient survival of AHA in Turkey.

Prospective registry of adult patients receiving therapeutic plasma exchange with a presumptive diagnosis of thrombotic microangiopathy (TMA): The Turkish hematology research and education group (ThREG)-TMA02 study.

Thrombotic microanjiopathy (TMA) is a pathological diagnosis characterized by abnormalities of small vessels leading to microvascular thrombosis of arterioles and capillaries. The current prospective, non-interventional, multicenter study aimed to define the distribution of different TMA forms in adult Turkish patients who were referred for therapeutic plasma exchange (TPE) for presumptive diagnosis of TMA. Patients with serum ADAMTS13 activity <5% were diagnosed as having acquired thrombotic thrombocytopenic purpura (aTTP). Patients presenting with ADAMTS13 activity 6-10 % / normal renal function and patients with ADAMTS13 activity >10 %, normal renal function and no secondary TMA were treated as unclassified TMA. The study included a total of 80 patients (women: 50; man: 30) with a median age of 48 (20-74). Detailed evaluation at 1 month after hospital admission revealed aTTP, secondary TMA, infection/complement-associated hemolytic uremic syndrome and unclassified TMA in 29 (36.2 %), 22 (27.5 %), 23 (28.8 %) and 6 (7.5 %) patients respectively. As subclassification of various TMAs will dictate specific therapy, proper diagnosis in a timely manner is of utmost clinical significance.

Prospective registry of adult patients receiving therapeutic plasma exchange with a presumptive diagnosis of thrombotic microangiopathy (TMA): The Turkish hematology research and education group (ThREG)-TMA02 study.

Thrombotic microangiopathy(TMA) is a pathological diagnosis characterized by abnormalities of small vessels leading to microvascular thrombosis of arterioles and capillaries. The current prospective, non-interventional, multicenter (n:18) study aimed to define distribution of different TMA forms in adult Turkish patients who were referred for therapeutic plasma exchange (TPE) for a presumptive diagnosis of TMA. Patients with serum ADAMTS13 activity <5% were diagnosed as acquired thrombotic thrombocytopenic purpura (aTTP). Patients presenting with ADAMTS13 activity 6-10 % / normal renal function and patients with ADAMTS13 activity >10 %, normal renal function and no secondary TMA were treated as unclassified TMA. The study included a total of 97 patients (female: 60; male: 30) with a median age of 48 (18-74). Detailed evaluation at 1 month after hospital admission revealed aTTP, secondary TMA, infection/complement-associated hemolytic uremic syndrome and unclassified TMA in 32 (33 %), 33 (34 %), 26 (27 %) and 6 (6%) patients respectively. As subclassification of various TMAs will dictate specific therapy, proper diagnosis in a timely manner is of utmost clinical significance.

Pralatrexate experience in PTCL: A multicenter retrospective study from Turkey.

PURPOSE: Pralatrexate is a new generation antifolate treatment agent used for the treatment of relapsed or refractory peripheral T-cell lymphomas. This study aims to determine the general characteristics of the patients receiving pralatrexate therapy in Turkey, contributing to the literature on the effectiveness of pralatrexate therapy in peripheral T-cell lymphomas by determining the response levels of such patients to the therapy. The study also attempts to clinically examine the major side effects observed in patients during treatment with pralatrexate. METHODS: The study included patients with peripheral T-cell lymphoma followed up in the hematology units of several hospitals in Turkey. Overall, 20 patients aged 18 and over were included in the study. RESULTS: The median age at the time of diagnosis was 58.5 years. PTCL-NOS (Peripheral T-cell lymphoma, not otherwise specified) subtype was in 40% of patients, making the PTCL-NOS the most common subtype in the study. In general, most patients were diagnosed with disease at an advanced stage. Pralatrexate therapy was given to the patients at a median treatment line of 3.5. Pralatrexate dose reduction was required in only 3 patients (15%). Response to pralatrexate therapy with partial remission (PR) and above was observed in 11 (55%) of the patients. CONCLUSION: Pralatrexate seemed to be a promising novel treatment in relapsed refractory PTCL patients. However, patients receiving pralatrexate should be followed up carefully for skin reactions, mucosal side effects, thrombocytopenia and neutropenia.

Efficacy and Safety of Ibrutinib Therapy in Patients with Chronic Lymphocytic Leukemia: Retrospective Analysis of Real-Life Data

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

Evaluation of clinical characteristics of patients with paroxysmal nocturnal hemoglobinuria treated with eculizumab in Turkey: a multicenter retrospective analysis.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare X-linked genetic disorder. On the contrary to its name, it is a multisystemic disease and various symptoms other than hemoglobinuria could be occurred. It could be life threatening especially because of thromboembolic events. In the last decade, a terminal complement inhibition with eculizumab approved with promising results for PNH patients. We conducted this study to evaluate the long term experience of eculizumab therapy from Turkey for the first time. Our cohort included 138 patients with PNH treated with eculizumab between January 2008 and December 2018 at 28 centers in Turkey. Laboratory and clinical findings at the time of diagnosis and after eculizumab therapy were recorded retrospectively. The median age was 39 (range 18-84) years and median granulocyte PNH clone size was 74% (range 3.06-99.84%) at the time of diagnosis. PNH with bone marrow failure syndrome was detected in 49 patients and the rest of 89 patients had classical PNH. Overall 45 patients (32.6%) had a history of any prior thrombotic event before eculizumab therapy and only 2 thrombotic events were reported during the study period. Most common symptoms are fatigue (75.3%), hemoglobinuria (18.1%), abdominal pain (15.2%) and dysphagia (7.9%). Although PNH is commonly related with coombs negativity, we detected coombs positivity in 2.17% of patients. Seven months after the therapy, increased hemoglobin level was seen and remarkably improvement of lactate dehydrogenase level during the treatment was occurred. In addition to previous studies, our real life data support that eculizumab is well tolerated with no serious adverse events and improves the PNH related findings.

Langerhans cell histiocytosis: A rare cause of pathological rib fracture.

Langerhans cell histiocytosis, formerly known as histiocytosis X, represents clonal proliferations of the antigen-presenting dendritic cells, which are normally found in many organs. It is a rare disease which tends to affect children and adolescents. In particular, adult-onset type is very rare. Herein, we present a female adult diagnosed with Langerhans cell histiocytosis of the rib without any systemic involvement which was successfully treated with surgery.

Peripheral Blood Smear Findings of COVID-19 Patients Provide Information about the Severity of the Disease and the Duration of Hospital Stay.

BACKGROUND: Data about the morphological changes in peripheral blood smears during COVID-19 infection and their clinical severity association are limited. We aimed to examine the characteristics of the cells detected in the pathological rate and/or appearance and whether these findings are related to the clinical course by evaluating the peripheral blood smear at the time of diagnosis in COVID-19 patients. METHODS: Clinical features, laboratory data, peripheral blood smear of fifty patients diagnosed with COVID-19 by PCR was evaluated at diagnosis. Peripheral smear samples of the patients were compared with the age and sex-matched 30 healthy controls. Pictures were taken from the patient's peripheral blood smear. Patients were divided into two groups. Mild and severe stage patient groups were compared in terms of laboratory data and peripheral smear findings. The relationship between the laboratory values of all patients and the duration of hospitalization was analyzed. RESULTS: The number of segmented neutrophils and eosinophils were low, pseudo-Pelger-Huet, pseudo-Pelger-Huet/mature lymphocyte ratio, atypical lymphocytes, monocytes with vacuoles, bands, and pyknotic neutrophils rates were higher in the peripheral blood smear of the patient group (p <0.05). Increased pseudo-Pelger-Huet anomaly, pseudo-Pelger Huet/mature lymphocyte ratio, a decreased number of mature lymphocytes, and eosinophils in peripheral blood smear were observed in the severe stage patients (p <0.05). A negative correlation was observed between hospitalization duration and mature lymphocyte and monocytes with vacuoles rates (p <0.05). CONCLUSION: A peripheral blood smear is an inexpensive, easily performed, and rapid test. Increased Pseudo-Pelger-Huet anomaly/mature lymphocyte rate suggests a severe stage disease, while high initial mature lymphocyte and monocytes with vacuoles rates at the time of diagnosis may be an indicator of shortened duration of hospitalization.

Efficacy and safety of ruxolitinib in patients with myelofibrosis: a retrospective and multicenter experience in Turkey

Background/aim: The aim of this study is to assess the efficacy and safety of ruxolitinib in patients with myelofibrosis. Materials and methods: From 15 centers, 176 patients (53.4% male, 46.6% female) were retrospectively evaluated. Results: The median age at ruxolitinib initiation was 62 (28­87) and 100 (56.8%) of all were diagnosed as PMF. Constitutional symptoms were observed in 84.7%. The median initiation dose of ruxolitinib was 30 mg (10­40). Dose change was made in 69 (39.2%) patients. Forty seven (35.6%) and 20 (15.2%) of 132 patients had hematological and nonhematological adverse events, respectively. The mean spleen sizes before and after ruxolitinib treatment were 219.67 ± 46.79 mm versus 199.49 ± 40.95 mm, respectively (p < 0.001). There was no correlation between baseline features and subsequent spleen response. Overall survival at 1-year was 89.5% and the median follow up was 10 (1­55) months. We could not show any relationship between survival and reduction in spleen size (p = 0.73). Conclusion: We found ruxolitinib to be safe, well tolerated, and effective in real-life clinical practice in Turkey. Ruxolitinib dose titration can provide better responses in terms of not only clinical benefit but also for long term of ruxolitinib treatment.

Enzyme Replacement Therapy in a Gaucher Family.

Gaucher disease is a lipid storage disorder due to deficiency of beta glucocerebrosidase. It's an autosomal recessive disease and as a result of this enzyme deficiency, glucocerebroside accumulates in various types of tissues like liver, brain spleen and bone marrow. We aimed to describe the effects of enzyme replacement therapy in three members of a family with Gaucher disease and to emphasize screening of the family members of the patients with Gaucher disease. Furthermore, late diagnosis and treatment in these patients have a minimal effect on improvement of the quality of life, and early diagnosis and treatment are very important in Gaucher disease.

A multicenter experience of thrombotic microangiopathies in Turkey: The Turkish Hematology Research and Education Group (ThREG)-TMA01 study.

Thrombotic microangiopathies (TMAs) are rare, but life-threatening disorders characterized by microangiopathic hemolytic anemia and thrombocytopenia (MAHAT) associated with multiorgan dysfunction as a result of microvascular thrombosis and tissue ischemia. The differentiation of the etiology is of utmost importance as the pathophysiological basis will dictate the choice of appropriate treatment. We retrospectively evaluated 154 (99 females and 55 males) patients who received therapeutic plasma exchange (TPE) due to a presumptive diagnosis of TMA, who had serum ADAMTS13 activity/anti-ADAMTS13 antibody analysis at the time of hospital admission. The median age of the study cohort was 36 (14-84). 67 (43.5%), 32 (20.8%), 27 (17.5%) and 28 (18.2%) patients were diagnosed as thrombotic thrombocytopenic purpura (TTP), infection/complement-associated hemolytic uremic syndrome (IA/CA-HUS), secondary TMA and TMA-not otherwise specified (TMA-NOS), respectively. Patients received a median of 18 (1-75) plasma volume exchanges for 14 (153) days. 81 (52.6%) patients received concomitant steroid therapy with TPE. Treatment responses could be evaluated in 137 patients. 90 patients (65.7%) achieved clinical remission following TPE, while 47 (34.3%) patients had non-responsive disease. 25 (18.2%) non-responsive patients died during follow-up. Our study present real-life data on the distribution and follow-up of patients with TMAs who were referred to therapeutic apheresis centers for the application of TPE.

Nodular lymphocyte predominant Hodgkin's lymphoma in daily practice: A multicenter experience.

Nodular lymphocyte predominant Hodgkin's lymphoma (NLPHL) is a rare subtype of Hodgkin's lymphoma. In this study, we aimed to investigate the clinical features and therapeutic outcomes of patients with NLPHL who were diagnosed at different institutes in Turkey. We retrospectively reviewed the records of the patients diagnosed with NLPHL. Adult patients who were diagnosed after 2005 with histological confirmation were selected for the study. Forty-three patients were included in the study. Median age of patients was 37.5 years (18-70) at the time of diagnosis. About 60.5% patients were diagnosed as stage I and II NLPHL, and remaining 39.5% had stage III and IV disease. Median follow-up was 46 months. During follow-up, none of the patients died. Seven patients relapsed or progressed after initial therapy at a median of 12 months. Five of 7 relapsed/refractory patients (71.4%) were salvaged with chemotherapy only (DHAP, ICE), and the remaining 2 (28.6%) were salvaged with chemoimmunotherapy. All of relapsed/refractory patients were able to achieve complete remission after salvage therapy. Lactate dehydrogenase levels were significantly higher in patients with progressive disease compared with nonprogressive disease. Our study showed an excellent outcome with all patients alive at last contact with a median follow up of 46 months despite a wide range of different therapeutic approaches. All relapsed and refractory patients were successfully salvaged despite a low frequency of patients received immunotherapy in conjunction with chemotherapy. Our results suggest that immunotherapy may be reserved for further relapses.