Treatment options in primary mediastinal B cell lymphoma patients, retrospective multicentric analysis; a Turkish oncology group study.

Introduction and Aim: Primary mediastinal B-cell lymphomas (PMBL) are aggressive B- cell lymphomas. Although the initial treatment models vary in PMBL, appropriate treatment methods are not known. We aim to show real-life data on health outcomes in adult patients with PMBL who received various type of chemoimmunotherapies in Turkey. Method: We analyzed the data of 61 patients who received treatments for PMBL from 2010 to 2020. The overall response rate (ORR), overall survival (OS) and progression-free survival (PFS) of the patients were evaluated. Results: 61 patients were observed in this study. The mean age of the study group was 38.4 ± 13.5 years. From among them, 49.2% of the patients were female (n = 30). For first-line therapy, 33 of them had received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) regimen (54%). Twenty-five patients had received rituximab, etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin (DA-EPOCH-R) regimen. The ORR was 77%. The median OS and PFS were as follows: 25 months (95% CI: 20.4-29.4) and 13 months (95% CI: 8.6-17.3), respectively. The OS and PFS at 12 months were 91.3% and 50%, respectively. The OS and PFS at five years were 64.9% and 36.7%, respectively. Median follow-up time period was 20 months (IQR 8.5-38.5). Conclusion: R-CHOP and DA-EPOCH-R showed good results in PMBL. These remain one of the best determined systemic treatment options for first-line therapy. Also, the treatment was associated with good efficacy and tolerability.

Variant hairy cell leukemia following papillary urothelial neoplasm of bladder.

A 65 years old man was admitted with multiple lymphadenopathy, weight loss, night sweats and fatigue for 2 months. He had been treated for bladder cancer 2 years ago. Leukocyte count was 37.9 x10(9)/l. Peripheral blood smear had 91% lymphocytes. Lymphocytes had large nuclei with prominent nucleoli, heterogeneous appearance, and large cytoplasm with hairy projections. Flow cytometric immunophenotyping revealed CD20, CD22, CD24, CD45 and HLA-DR positivity. Atypical lymphocytes were stained with tartrate resistant acid phosphatase. Increased metabolic activity was detected in multiple lymph nodes, bone marrow and extremely enlarged spleen with positron emission tomography-computed tomography. Excisional biopsy of the left axillary lymph node revealed infiltration with diffuse B-cell leukemia/lymphoma. Immunohistochemistry showed CD20 positive atypical cells with weak expression of CD11c. The patient was diagnosed as a case of variant hairy cell leukemia and cladribine was administered. A probable second primary malignancy should be kept in mind in cases with a defined malignancy in the presence of unusual symptoms.

Effect of galantamine on platelet functions in healthy elderly people.

BACKGROUND & OBJECTIVES: Galantamine, a centrally-acting cholinesterase inhibitor, has been used in the treatment of mild-to-moderate dementia of Alzheimer disease. Increased mortality, mainly due to cardiovascular events, was observed in placebo-controlled trials of galantamine. Several studies have evaluated the efficacy of galantamine in dementia, it is not clear whether it has an effect on platelet function. It is important to clarify this effect, because it may be related to thrombotic tendency or bleeding diathesis. This study was aimed to investigate the effect of galantamine on platelet aggregation in whole blood from healthy, elderly subjects. METHODS: Fifteen healthy (mean age 76.8 ± 7.2 yr) volunteers were included in the study. Three concentrations of galantamine solution (20, 40 and 80 ng/µl) were prepared. Each concentration of galantamine solution and control diluent without galantamine were incubated with whole blood. After incubation, aggregation responses were evaluated with ADP (5 µM) and collagen (2 µg/ml) in platelet-rich plasma. RESULTS: Compared to control, pre-incubation with all dilutions of galantamine had no detectable effect on platelet aggregation response induced by ADP and collagen. Galantamine also had no detectable effect on platelet aggregation in a dose-dependent manner. INTERPRETATION & CONCLUSIONS: This in vitro study suggested that galantamine administration had no effect on platelet aggregation in the clinically relevant doses.

Reactive thrombocytosis accompanying subclinical hypothyroidism due to Hashimoto's thyroiditis.

The important thing in a patient in whom platelet values were detected to be greater than normal is whether thrombocytosis is a reactive phenomenon due to a different pathology or due to a clonal hematological pathology. In this case report, reactive thrombocytosis observed in a case with subclinical hypothyroidism due to Hashimoto's thyroiditis is reported; and according to our literature review, this is the first reported case of reactive thrombocytosis due to Hashimoto's thyroiditis and/or subclinical hypothyroidism. A 31-year-old man without any complaint was admitted to the Hematology Department for thrombocytosis which was detected in his routine follow-up. He had been using thyroid hormone replacement for 2 years because of hypothyroidism as Hashimoto's thyroiditis was earlier diagnosed. Due to miscommunication, he stopped his medication levothyroxine 0.1 mg/day 2 weeks in advance and he was still off-drug on admission. Platelet count was 715×10/l in the first admission center. Subclinical hypothyroidism diagnosis was made with the present findings and thyroid hormone replacement therapy was again commenced gradually. Platelet counts and thyroid-stimulating hormone value were normal 6 weeks later. As a result, before making diagnosis of thrombocytosis related to myeloproliferative disease or myelodysplastic syndromes, secondary causes should be investigated carefully.

A case of rhinoorbital mucormycosis in a leukemic patient with a literature review from Turkey.

Mucormycosis (Zygomycosis) is a rare, invasive, opportunistic fungal infection of the paranasal sinuses, caused by a fungus of the order Mucorales. We report a case of rhinoorbital mucormycosis caused by Rhizopus oryzae in an acute lymphoblastic leukemia patient and review the 79 Mucormycosis cases reported in the last decade from Turkey. In our case, the diagnosis was made with endoscopic appearance, computerized tomography of the paranasal sinuses, and culture of the surgical materials. Following aggressive surgical debridement and parenteral amphotericin B therapy, the patient recovered completely. In Turkish literature, rhinocerebral manifestations were the most common form of the mucormycosis (64 cases), followed by pulmonary form (6 cases). The most common risk factor was hematologic malignancies (32 cases) and diabetes mellitus (32 cases), similar to those reported from the rest of the world. The etiologic agents responsible for the review cases were Rhizopus sp., Mucor spp., Rhizomucor spp., Rhizopus oryzae, Mucor circinelloides, and Lichtheimia corymbifera. Although various treatment modalities were used, amphotericin B was the mainstay of therapy. Mortality rate was found to be 49.4% in review cases. It seems that strong clinical suspicion and early diagnosis, along with aggressive antifungal therapy and endoscopic sinus surgery, have great importance for better prognosis in mucormycosis.

Serum vitamin B12 and homocysteine levels in pregnant women with neural tube defect.

OBJECTIVE: The aim of the study is to investigate the importance of serum vitamin B12 levels in pregnant women with foetal neural tube defect (NTD). STUDY DESIGN: This study consists of 31 pregnant women having fetuses with NTD. The pregnant women in the study group were selected among cases with normal folate levels. Serum vitamin B12 levels were investigated. Additionally, complete blood count, serum iron level, iron binding capacity, ferritin, folate, free T(3), free T(4), thyroid stimulating hormone and plasma homocysteine levels were measured. Control group consisted of 32 pregnant women who did not have a history of NTD in previous pregnancies and did not have fetuses with NTD in present pregnancy. NTD was diagnosed between 14th and 20th gestational age. The mean gestational age of members of control group was the same as those of NTD group. RESULTS: There was no statistically significant difference between pregnants with NTD and control group according to number of cases with vitamin B12 deficiency. CONCLUSION: It seems that vitamin B12 deficiency does not play a causative role in the development of foetal NTD. Monitoring maternal homocystein levels might be important in understanding the aetiologies of foetal NTD.

Multiple myeloma presenting with acquired factor VIII inhibitor.

An initial presentation of hematological malignancies associated with autoantibodies is not common, and there is only one documented case of multiple myeloma presenting with acquired FVIII inhibitor for multiple myeloma. In this paper, we describe a second case of multiple myeloma who presented with acquired FVIII inhibitor. A 43-year-old woman was referred to our hematology unit for anemia and an elevated erythrocyte sedimentation rate. Two months before her admission, she had undergone an operation at a local hospital because of ovarian cyst rupture complicated by severe postoperative bleeding. Because coagulation tests had revealed a prolonged partial thromboplastin time which could not be corrected by a mixing test and a decreased FVIII level, a diagnosis of acquired FVIII inhibitor had been made. The patient was hospitalized in our unit for further evaluation. The erythrocyte sedimentation rate was 110 mm/h, serum albumin level 2.5 g/dL, globulin level 5.6 g/dL, and C-reactive protein 47.8 mg/L (0-6). Serum IgG was high, and serum protein electrophoresis showed a monoclonal spike in the gamma region. An IgG-kappa paraprotein was identified by immunofixation of the urine and serum. X-ray films of the bones revealed lytic areas in the skull, pelvis, and lumbar vertebrae. Bone marrow aspiration showed normal cellularity with 40% plasma cell infiltration. The patient was diagnosed with the IgG kappa type of multiple myeloma associated with acquired FVIII inhibitor. In patients presenting with severe bleeding, autoantibodies against FVIII should be considered for the differential diagnosis of bleeding. Clinicians should be alert to the presence of rare underlying neoplastic diseases such as multiple myeloma, in patients with acquired FVIII inhibitor.

Platelet-derived microparticle levels in women with recurrent spontaneous abortion.

OBJECTIVE: To investigate the significance of platelet-derived microparticles (PMPs) in women with recurrent spontaneous abortion. METHODS: We measured platelet P-selectin (CD62P) as a platelet activation marker and CD42b(+) microparticles as PMPs by flow cytometry in whole blood of 20 women with recurrent spontaneous abortion and 20 age-matched healthy controls with no previous history of spontaneous abortion. RESULTS: PMP levels in women with recurrent spontaneous abortion were higher than in women in the control group (4.79+/-1.18% vs 3.06+/-0.92%; P<0.000). CD62P levels were not significantly higher in the study group compared with the control group (13.78+/-8.62% vs 10.78+/-7.35%; P>0.05). CONCLUSION: Our findings suggest that PMPs may have a role in the pathogenesis of recurrent spontaneous abortion.

Levosimendan has an inhibitory effect on platelet function.

Levosimendan enhances cardiac contractility by increasing myocyte sensitivity to calcium, and induces vasodilatation. Although studies have evaluated the efficacy of levosimendan in heart failure, it is not clear whether it might produce functional influence on platelet response. In this study, the effect of levosimendan on platelet aggregation was investigated. Platelet function tests were performed in 12 healthy male volunteers. Three concentrations of levosimendan solution were prepared that would result in 10, 25, and 45 ng/ml levosimendan concentrations in the blood similar to that observed after clinical therapeutic intravenous application of 0.05-0.1 microg/kg/min. Each concentration of levosimendan solution and a control diluent without levosimendan were incubated with whole blood at 37 degrees C. After incubation for 15 min, aggregation responses were evaluated with adenosine diphosphate (ADP) (5 and 10 microM) and collagen (2 and 5 microg/ml) in platelet-rich plasma. Preincubation with all dilutions of levosimendan inhibited aggregation of platelets induced by ADP and collagen significantly. Levosimendan also inhibited significantly the secondary wave of platelet aggregation induced by ADP. The results showed that there was a relationship between levosimendan concentration and inhibition of platelet aggregation. In conclusion, this study with an in vitro model showed that levosimendan had a significant inhibitory effect on platelets in clinically relevant doses.

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) promotes in vitro platelet aggregation.

rhG-CSF is increasingly used for stimulation of granulopoiesis and stem cell mobilization in healthy donors for allogeneic stem cell transplantation. However, a possible association between thrombosis and rhG-CSF administration has been reported. For that reason, in this study, we investigated the effect of rhG-CSF on platelet aggregation in whole blood of 10 healthy volunteers. Three concentrations of rhG-CSF solution (1, 10 and 100 ng/ml) were prepared. Each concentration of rhG-CSF solution and a control diluent without rhG-CSF were incubated with whole blood. Incubation with rhG-CSF solutions would result in 0.1, 1.0 and 10 ng/ml rhG-CSF concentrations in the blood. After incubation, aggregation responses were evaluated with ADP (5 and 10 microM) and collagen (2 and 5 microg/ml) in whole blood. When compared to control, preincubation with all dilutions of rhG-CSF augmented aggregation of platelets induced by ADP and collagen in a statistically significant manner (p < 0.05 for all comparisons). There was also a relationship between rhG-CSF concentration (1, 10 and 100 ng/ml) and augmentation of platelet aggregation response (p < 0.0001 for 5-10 microM ADP; p < 0.0001 for 2-5 microg/ml collagen). In conclusion, this study with an in vitro model showed that rhG-CSF administration may lead to platelet hyperaggregability.

The effect of radiologic imaging studies on the risk of secondary malignancy development in patients with Hodgkin lymphoma.

PURPOSE: Recently, reports have been published, which suggest that diagnostic radiologic imaging studies could play a role in the risk of secondary malignancy development in patients with cancer. The aims of our study are to calculate the average amount of accumulated radiation dose gained by means of radiologic imaging studies performed intensively in diagnosis and follow-up of patients with Hodgkin lymphoma and to evaluate whether this amount of accumulation accounts for a real risk for secondary malignancies. PATIENTS AND METHODS: This study consists of 15 male patients, whose mean age was 23.67 years +/- 4.24 years. All radiologic imaging studies performed in patients with Hodgkin lymphoma were noted in detail, and average radiation dose accumulation was calculated. RESULTS: Median radiation doses to which patients were subjected during a median of 14.5 months of disease duration were 85.19 mSv and 161.08 mSv according to data of the National Radiological Protection Board and Biological Effects of Ionizing Radiation VII report, respectively. The cumulative radiation dose, because of radiologic imaging studies, is 8.5-16-times greater than that of the described dose having 1 in 1,000 chance of cancer development according to Biological Effects of Ionizing Radiation VII report. Approximately, this amount is equivalent to the dose of natural background radiation received during 35-70 years. CONCLUSION: Our study demonstrated that radiation dose accumulation because of radiologic imaging studies used in diagnosis, staging, and follow-up of patients with Hodgkin lymphoma was high enough to cause development of secondary malignancies. Finally, it is obvious that the radiologic imaging study policies used in follow-up of these patients should be overviewed.