Journal du sang et de la lymphe

Background: Chronic venous disease (CVD) is a common clinical condition, especially relevant for its impact on public health and its related economic burden. Veno-Active Drugs (VAD) are an heterogeneous group of drugs, widely used in the treatment of CVD. In the last years some food supplements, similar to VAD but with different compounds concentrations raised some confusion in this field. The complex Lypoic acid, Ginkgoselect phytosome and Leucoselect phytosome is a food supplement based on molecules exhibiting different but synergic activities never prospectively tested in patients with CVD. Methods: Consecutive ambulatory patients with objectively documented CVD and a CEAP “C” up to 5 were eligible for the study. Patients were to take 1 fast-slow tablet of the complex twice-daily for 2 months, followed by 1 fast-slow tablet once-daily for other 4 months, for a total of 6 months. Presence and magnitude of CVD-related signs and symptoms (with “C” of the CEAP classification), evaluation of patients’ quality of life (with VEINES-QoL/Sym questionnaire) and assessment of safety and tolerability of the complex at baseline and after 2 and 6 months (with revised Venous Clinical Severity Score, rVCSS) were recorded. Results: 97 patients enrolled and evaluated. The proportion (65%) of the patients with a rVCSS score>5 at baseline decreased to 35% at 6 months (P <0.001). The number of patients with a scoring of “none” for the item “Pain or other discomfort” increased from 8% at baseline to 54% at 6 months (P=0.001). The pairwise comparison yielded significant results between the 3 time-points for the rVCSS (p<0.00001) and the VEINES-Sym (p<0.00001), while for the VEINES-QoL score between the baseline and the end of the study only (p=0.0016). Conclusion: The complex Lypoic acid, Ginkgoselect phytosome and Leucoselect phytosome seems beneficial for reducing leg complaints, and effectively improves QoL in patients with CVD.

We report adult patients with myelodysplastic syndrome with excess blast (MDS) by the world health organization (WHO) 2016 revision for classification of myeloid neoplasm group. The case had clinical and hematological peculiarities, which had rarely reported and described yet. The cytogenetic alterations were complex translocation 9;22;19 (Variant Philadelphia+) of Philadelphia chromosomes which appeared at different moments of the disease. The patient showed the Ph chromosome with disease transformation at diagnosis and unfortunately, further workup could not be performed as the patient succumbed to her illness and expired. The complex characterization with multiple translocations and the presence of Ph could be a marker of this form of MDS. The association of clinical and hematological findings suggests the possibility of a new group of adult MDS.

Objective: Two patient groups were studied for evaluation of detection efficacy of 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging (18F-FDG PET/MRI). The first group was dedicated to assess the possible early bone lesions of those patients who had been diagnosed with monoclonal gammopathy of undetermined significance/smouldering multiple myeloma (MGUS/SMM). In the second group, the detection sensitivity of the PET/CT and PET/MRI for bone lesions was compared to each other in patients with symptomatic plasmacytic myeloma (PCM).
Methods: 14 patients with MGUS/SMM and 27 patients with PCM were enrolled in this study. Initially, all patients underwent an 18F-FDG PET/CT examination and it was followed by a PET/MRI imaging.
Results: No bone lesion was detected with PET/CT and PET/MRI in patients either with MGUS and SMM. Bone marrow alteration was also not detected with PET/MRI in this group. Disease progression has not been revealed in the course of the 18 months follow-up period. In regard to lesion detection, there was no difference between the PET/CT and PET/MRI in the symptomatic PCM group. The metabolic tumor volume (MTV) was found to be strongly correlating with both the β2-microglobulin serum level and the ISS stage.
Conclusion: PET/MRI is a reliable diagnostic tool for detection of bone lesions in plasma cell discrasias, and it is not inferior to the PET/CT imaging. The MTV measurement can provide a promising diagnostic tool for the direct assessment of myeloma tumor loading in the future.

Patients with β-thalassemia intermedia are at increased risk of thromboembolic events and multifactorial pulmonary arterial hypertension. A pro-thrombotic state, including decreased levels of natural anticoagulant proteins and chronic platelet activation, has been shown in these patients, in particular after splenectomy.

We report the case of a 54-year-old splenectomized β-thalassemic patient with a history of unprovoked deep venous (femoro-politeal) thrombosis, complicated by a pulmonary embolism event at the age of 37, recurrent episodes of superficial vein thrombosis of the lower limbs with leg ulcers, and a progressive severe pulmonary arterial hypertension, related to recurrences of pulmonary embolism, despite long-term, well conducted oral anticoagulant treatment (vitamin K antagonists and apixaban). After the performance of a right heart catheterization, pulmonary endarterectomy was not considered indicated in this patient because of the distal localization of thrombi. Aspirin treatment was added to vitamin K antagonists. Riociguat and ambrisentan therapy induced an improvement of both symptoms and echocardiographic picture over 12-mo follow-up.

Splenectomized thalassemic patients are at high risk of thromboembolic events, and pulmonary hypertension, despite common, is yet a poorly understood complication. Clear recommendations on the management of such condition are lacking due to the limited data regarding the use of vasodilators, anticoagulants (vitamin K antagonists, heparins, direct oral anticoagulants) and antiplatelet agents.

Objectives: Thrombosis is a leading cause of morbidity and mortality in patients with Philadelphia negative chronic myeloproliferative neoplasms (MPNs). There are many thrombosis risk stratifications used in this patient group taking into consideration the age, thrombosis history and cardiovascular factors (hypertension, hypercholesterinaemia, hyper-trigliceridaemia, thrombocytosis, smoking and diabetes mellitus). In this work we evaluated the possible role of iron deficiency in thrombotic events (TE) of the polycythaemia vera (PV) patients. Methods: We considered the low mean cell haemoglobin (MCH <28 pg) value as a parameter to assess the iron deficiency in the multicentre database (15 Hungarian haematology centres) of our HUMYPRON GROUP (Hungarian MPN Working Group). The MCH values, recorded at the time of diagnosis of 296 patients with polycythemia vera, were retrospectively analysed.
Results: The low MCH, at the diagnosis, was found to be a risk factor for thrombotic events occurring after diagnosis (OR: 1.966). It was also shown as an additive and independent parameter in the Tefferi high-risk patient groups, and combining it with Tefferi risk stratification an extremely high thrombotic risk group could be determined (Nagelkerke R square: 0.084). We have supposed that low MCH in PV reveals a disease form featured with a high proliferation activity. Our hypothesis was confirmed with a sub-study (n=52) showing that the high JAK2V617F allele burden was significantly correlated with the low MCH (p=0.005) and the high white blood cell count (WBC) (p<0.001).
Conclusions: Iron deficiency, existing at the time of diagnosis of PV, was proven to be a risk factor for imminent thrombotic events. The low MCH was found to be a strong additive factor when it was combined with the known thrombotic risk stratification systems. The low MCH showed significant correlation with the high JAK2V617F allele burden.

Introduction: There is debate regarding the use of busulfan every 6 hours (q6 h) compared to every 24 hours (q24 h) in patients undergoing hematopoietic cell transplantation.
Objectives: To review the literature to determine whether there is a significant difference between dosing busulfan q6 h vs. q24 h in adults, and to review dosing strategies to optimize daily dosing.
Methods: A literature search was conducted in PubMed with the terms “busulfan” and “transplant” and “24” in all fields. Results were further refined by using the terms “busulfan” and “transplant” and “pharmacokinetics”. Titles were then reviewed for relevance, and the remaining articles reviewed by abstract. Articles deemed relevant were then read in more thorough detail, and references cited by these articles reviewed to ensure a comprehensive review of the literature. Studies focusing on the pediatric population were not reviewed.
Results: 478 articles were identified, and of these, 372 contained the term “pharmacokinetics”. Based on abstract review, 26 relevant articles were identified. All articles confirmed that there are no differences in the pharmacokinetics of q6 h vs. q24 h dosing, and that safety appears equivalent between the two dosing schemes. One study noted an increase in the occurrence of acute graft-vs.-host disease (GVHD) and possibly increased gastrointestinal (GI) toxicity and stomatitis with q6 h dosing, while another noted a higher incidence of toxicity with q24 h dosing specifically in metastatic renal cell carcinoma patients. All articles concluded that both regimens are equally effective, but that q24 h dosing is more convenient and likely to decrease hospitalization, nursing, and pharmacy requirements.
Conclusions: There is no difference in efficacy or safety between busulfan q6 h and q24 h dosing. Institutions should consider moving to daily dosing of busulfan for improved convenience and decreased costs.

Purpose: The aim of this study is to indicate a successful standard chemotherapy in metastatic dysgerminoma with extension to the kidney.
Case: The present submission is a case report of a right ovarian gonadoblastoma and a left ovarian dysgerminoma metastatic to the para-aortic lymph nodes with extension to the left kidney in a 21-year-old woman ultimately diagnosed with familial Swyer syndrome. The patient underwent bilateral salpingo-oophorectomy followed by 4 cycles of BEP and is without evidence of disease at nine-month follow-up.
Result: This is basically a report of successful administration of standard of care. Familial cases of Swyer syndrome have indeed been described. The risk of gonadoblastoma and dysgerminoma in women with Swyer syndrome is ~15-30% and current practice is to perform bilateral gonadectomy, as was done in this case. In advanced stage, incompletely resected dysgerminoma, complete clinical response was 90% to BEP chemotherapy. Further, 95% of patients remained disease free with prolonged follow-up.
Conclusion: Thus, it is excellent response rates to BEP chemotherapy, it is standard of care to spare patients from high surgical morbidity and administer BEP chemotherapy instead. We recommend in such cases with extended tumoral involvement which surgery seems to be dangerous, due to large vessel invasion, we can start chemotherapy first, then re-evaluate, in presented case metastasis of dysgerminoma completely responded to chemotherapy and prevented the nephrectomy.

Assisted reproductive technologies (ART) seem to have a double way clinical association with hypercoagulation and possible thrombotic complications: venous thromboembolism (VTE) seems to be not frequent complications in women that perform ART but its incidence seem to be increased if compared to that related to spontaneous pregnancy. Several mechanisms support this clinical association such as pharmacological ovarian stimulation and its induced acquired thrombophilia, possible presence of inherited thrombophilia that represents a risk to develop VTE per se and the occurring of pregnancy with its spontaneous hypercoagulable state.
Yet in the daily clinical management the frequent use of antithrombotic drugs as aspirin and low molecular weight heparin to increase the rate of pregnancy after ART procedure may be a confounding factor to support this aspects in this clinical settings.

Introduction: The prognosis for mantle cell lymphoma (MCL) has remained poor despite the current use of autologous transplantation and induction chemotherapy that includes high-dose cytarabine. The introduction of rituximab and bendamustine, however, has led to the improvement of prognosis of diffuse large B-Cell lymphoma and indolent lymphoma. For these reasons, we analyzed the effectivity of rituximab maintenance therapy and bendamustine against mantle cell lymphoma at our hospital.
Methods: We selected 22 cases of MCL for which treatment was initiated between January 2004 and December 2016 at our hospital. We compared the cases based on the use of rituximab maintenance therapy or bendamustine, simplified Mantle Cell Lymphoma International Prognostic Index (sMIPI), staging, and treatment regimens to analyze the effect of rituximab maintenance therapy and bendamustine on prognosis.
Results: Overall five-year survival rate was 67%. Significant difference (P=0.0432) was observed in the 5-year survival rate between the group treated with rituximab maintenance therapy (90.9%) and the group that was not (56.2%). Likewise, significant difference (P=0.0197) was observed in the 5-year survival rate between the group that received bendamustine during the course of treatment (90.9%) and the group that did not (50%). Majority of the cases in the group that received bendamustine, however, had been treated with rituximab maintenance therapy.
Conclusion: Our study showed an improvement in prognosis of MCL due to the treatment with rituximab maintenance therapy and bendamustine. Although the analysis was conducted on a limited number of cases, we believe that rituximab maintenance therapy and treatments that include bendamustine are promising therapies for MCL.

Background: This study evaluated the effects of ABO blood groups on blood pressure indices.

Materials and methods: Eighty apparently healthy young adults between the ages of 18 and 40 years were purposively selected for the study. Twenty participants of blood group AB were first identified through mass blood group screening process and 20 age and sex-matched participants each of the other three blood groups were also selected for the study. Two millilitres of venous blood was obtained from superficial cubital vein of each participant into a Sodium Ethylene Diamine Tetra-acetic Acid (EDTA) anticoagulant bottle for blood grouping following standard procedure using anti-sera A, B and AB. Blood pressure was measured in sitting position after 5 minutes of rest with digital sphygmomanometer (Omron) and the BP indices were derived from systolic, diastolic and pulse rate. Comparison of means of parameters among the four blood groups was done using Analysis of Variance (ANOVA) and Duncan Post-hoc test. A p value of <0.05 was taken as statistically significant.

Results: The highest mean systolic, diastolic blood pressure, heart rate, mean arterial blood pressure and rate pressure product were found in blood group O while the highest mean pulse pressure was found in blood group AB. The effects of ABO blood group on blood pressure and its indices were not statistically significant. This study showed that ABO blood group system does not significantly affect blood group indices.

Distal deep venous thrombosis (DDVTs) is one of the “grey” areas of venous thromboembolism. There is a great heterogeneity in the diagnostic and therapeutic strategies between all the diagnostic centers. Studies doesn’t clarify the problem so it is not clear yet if there is any advantage in diagnosing and consequentially treating all the IDDVT. The 2012 ACCP guidelines suggested clinical observation for 2 weeks over initial anticoagulation (grade 2C) in patients with acute IDDVT without severe symptoms or risk factors for extension.

The existing methods of chemotherapeutic treatment do not permit to calculate the precise dose of medicine and the time of its action on the tumor that leads to the unpredictability of result, and, therefore, to the ineffectiveness of the use of treatment itself. Furthermore, the damage of normal cells on the chemotherapy becomes the reason for a whole series of the complications, connected with side-effects action of the chemotherapy. The paper presents the developed mechanism of processing of the fundamentally new form of anti-tumorigenic medicines with the calculated precise dose of the action of cytostatic on the tumor cells at the moment of their mitosis (indirect division of cells).

The new form of anti-tumorigenic medicines is a support material with the equally distributed spherical drops of cytostatic. The support material, thus, is a solid at room temperature and is melted at human body temperature, during its implanting into the body parts of patient, which supply the tumor by the blood, will dosed act directly on tumor cells at the moment of their mitosis using the equally distributed drops of cytostatic.

Any treating chemotherapist can calculate impact dose and time of the action of cytostatic that fall accurately on the mitosis of cancerous cells if he knows the volume of each drop and their total quantity in the support material, and also the time of melting of the support material. The calculated dose of cytostatic in the support material is reached by the injection of the assigned by chemotherapist volume of the cytostatic in the form of the spherical drops through the specific gap inside the camera for the molten support material by way of bubbling in the weightlessness conditions.

Rivaroxaban is one of most common used DOACs in the treatment of VTE. Rivaroxaban has been tested in a series of premarketing studies and after it has been used in non-interventional studies and in real life studies.
All studies experienced that rivaroxaban shows relevant safety concerning main outcomes of VTE therapy as recurrent VTE and major bleedings, in particular in patients that show similar clinical characteristics to those selected for EINSTEIN studies. Suggested doses of rivaroxaban seem to be safe also in real life studies while non-conventional doses may be associated to increased rate of clinical complications as recurrent VTE and major bleedings. Rivaroxaban shows also good safety when used in real life studies in patients with clinical characteristics that differ from those of patients in the EINSTEIN studies.

Clinical presentation of acute intermittent porphyria before puberty is unusual. We diagnosed the non-erythroid variant form of this disease in a male child, who first presented, at the age of 6 years, with unexplained neurological symptoms and behavioural abnormalities. We also report the successful treatment, and the long-term clinical management.