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Open access

Ariana Neicu, Maria Neagu, Maria Dobre, Roxana Ivan and Camelia Dobrea

Abstract

The goal of this study, part of the PERSOTHER project, is the implementation a new ancillary technique - fluorescent in situ hybridization (FISH) - in Burkitt lymphoma (BL) diagnosis, for the first time in our country. BL is a B-cell lymphoma with a highly aggressive clinical course. Three clinical variants of BL are recognized: endemic BL (in equatorial Africa), sporadic (throughout the world) and immunodeficiency-associated BL. The 2008 World Health Organization (WHO) Classification described a new category of B-cell lymphoma, unclassifiable, with intermediate features between diffuse large B-cell lymphoma (DLBCL) and BL. Because the treatment of BL is very aggressive, with high doses chemotherapy, an accurate diagnosis is required. Cytology, morphology and immunophenotype (CD20+, CD10+, BCL6+, BCL2-, Ki67 98-100%) are typical for BL. Most of the cases have MYC translocation at band 8q24 to the IgH region, 14q32. The demonstration of MYC translocation is necessary for BL diagnosis and differential with DLBCL and borderline cases. 22 cases of BL were evaluated by FISH for MYC translocation. 17 cases were positive, one case was negative and 4 cases were inconclusive. The results are concordant with the literature: the authors report about 10% MYC negative cases. In this cases micro-RNA (MiRNA-s) alterations may be implicated. The present study highlights the importance of FISH in BL diagnosis. It also identifies some of the technical difficulties of this method and it represents a basis for future routine diagnosis of selected BL cases.

Open access

Andreea Jercan, Rusu Munteanu Gina, Camelia Dobrea, Daniel Coriu and Aurelia Tatic

Abstract

Hereditary spherocytosis is an inherited hemolytic anemia due to red cell membrane defects, characterised by chronic hemolysis with different severity degrees, splenomegaly and microspherocytosis on the peripheral blood film.

Among the possible complications in these patients are aplastic crisis and extramedullary hematopoiesis.

In this article we present the case of a 42 years old man with hereditary spherocytosis diagnosed during childhood (average haemoglobin (Hb) value of 11-12 g/dl), which presented with worsening anemia, fever, chills, bone and muscle pain. The evolution was with accentuation of anemia (Hb 4.2 g/dl), decease of reticulocyte number (Ret 0,8%) and bilirubin (indirect bilirubin 2.7 g/dl). ParvovirusB19 DNA was 100.000.000 copies/ml. A computer tomography (CT)scan was performed and showed extramedullary hematopoiesis areas situated paravertebraly in the inferior thorax and hepatosplenomegaly. The infectious episode was self-limited and improved with substitution treatment.

Open access

D. Adam, Gina Burduşa, D. Iftimie, Ioana Hornea, Camelia Dobrea and Sorina Nicoleta Badelita

Abstract

Objective: Primary bilateral dumbbell-shaped lumbar non-Hodgkin lymphomas with epidural and extraspinal involvement, are rare occurrences. Patients presenting at advanced stages and rapid evolution towards neurological impairment lead to diagnostic dilemmas for which only immunohistochemistry can provide a correct, although delayed solution.

Case report: We report the first case of a bilateral, dumbbell-shaped, lumbar lymphoma in a 65-year-old man with a medical history of chronic viral hepatitis type B and D under interferon treatment. The patient presented with back pain radiating down the right leg, with rapid progression to paraplegia and sphincter dysfunction. CT and MRI revealed a large dumbbell mass (approx. 5/5/10 cm) in the right paraspinal musculature, at the L4-L5 level, with intraspinal epidural extension. A similar mass of smaller size was described on the left side, almost mirroring the first lesion, the imagistic aspect suggesting a neural sheath tumor. Intraoperatively, in the right lumbar paraspinal musculature, a soft, yellowish region was discovered, the macroscopic appearance being rather suggestive for a diffuse infection. Clinical, imagistic and surgical findings were not conclusive, nor was the histological examination in light microscopy of the surgical specimen or of the bone marrow biopsy. Immunohistochemistry identified the presence of large B cells, leading to the diagnosis of B cell lymphoma. Although the patient was treated with systemic chemotherapy, his condition rapidly deteriorated and he died within 3 months.

Conclusions: In the case of a lumbosacral, dumbbell shaped mass, developed both epidural and extraspinal, the differential diagnosis must include lymphoma. The histological examination, especially immunohistochemistry provided the final diagnosis. Delays in establishing a diagnosis, associated with a malignant evolution of lymphoma, diminish the chances of determining and applying a treatment strategy that could prolong survival.

Open access

Melen Brinza, Cerasela Jardan, Didona Vasilache, Camelia Dobrea and Daniel Coriu

Abstract

Background: Aplastic anemia (AA) is a rare and serious disease characterized by pancytopenia and hypoplastic bone marrow in the absence of infiltrates/fibrosis. It occurs more frequently in childhood and young adulthood (10-30 years) and with older age (>60 years), with equal distribution among men and women. As hypoplastic myelodysplastic syndromes (hMDS) are also associated with cytopenia and hypocellular marrow,they may be difficult to differentiate from AA. The presence of dysplastic features (others than erythroid) and/or blast cells >5% is essential to distinguish hMDS from AA. Cytogenetic tests may reveal clonal evolution in hMDS. As the two disorders differ greatly in means of management and prognosis, the correct diagnostic is very important.

Case presentation: We report the case of a 39 years old female diagnosed in 2005 (at age 29) with aplastic anemia. She received treatment with corticosteroids, Cyclosporine, blood transfusions and growth factors with partial response and no transfusion independency. After 8 years of evolution she developed dysplastic features within the megakaryocytic and granulocytic lineages and an increase in the blast population. The bone marrow slowly became hypercellular. The treatment with cyclosporine and growth factors was stopped.

Open access

Mihaela Cîrstea, Adriana Coliță, Bogdan Ionescu, Didona Vasilache, Camelia Dobrea, Cerasela Jardan and Mihaela Dragomir

Abstract

Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell disorder that is characterized by the presence of an absolute monocytosis (1 × 10^ 9/l) in the peripheral blood, the overlap of myelodisplastic aspects and myeloproliferative aspects in the bone marrow and tendency to transform into acute myeloid leukemia. CMML is considered to be the most aggressive chronic myeloid leukemia. We present the case of a 48 years old woman who was hospitalized in March 2013 in the Center of Hematology and Bone Marrow Transplantation for anemia related symptoms. Initial investigations showed anemia, relative monocytosis (10% monocytes of the WBC differential) with an increasing absolute number of monocytes (> 1,000/μl) in the following months. Initial exploration of the bone marrow (aspirate and bone marrow biopsy and immunohistochemistry IHC tests) revealed elements of trilinear dysplasia and an increased percentage of myeloblasts (11-14%). In the next four months myeloblasts percentage remained below 20% (8-14%) and it has been observed a gradually increasing of monocytoid elements (> 20%). Immunophenotyping in the bone marrow aspirate identified a monocytic proliferation with high percentage (8%) of immature cells. The karyotype reported the presence of clones with t (1;3). Initially diagnosed as RAEB-2 (WHO) the case was recomitted in CMML-type 2 with a progression to acute myeloid leukemia (AML). Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been performed after getting the best possible therapeutic response with AML chemotherapy type (complete remission). Allo-HSCT was performed using myeloablative conditioning, 12 months after diagnosis. The patient is now in complete remission, 24 months after allo-HSCT.

Open access

Mihaela Cîrstea, Adriana Coliță, Bogdan Ionescu, Alexandra Ghiaur, Didona Vasilescu, Camelia Dobrea, Cerasela Jardan, Mihaela Dragomir, Anca Gheorghe, Zsofia Várady and Anca Roxana Lupu

Abstract

In the 2016 revision of the World Health Organization classification the term therapy-related myeloid neoplasia (t-MN) defines a subgroup of acute myeloid leukemia (AML) comprising patients who develop myelodysplastic syndrome (MDS-t) or acute myeloid leukemia (AML-t) after treatment with cytotoxic and/or radiation therapy for various malignancies or autoimmune disorders. We report the case of a 36 year old patient with t-MN (t-MDS) after achieving complete remission (CR) of a PML-RARA positive acute promyelocytic leukemia (APL) at 32 months after diagnosis. Initially classified as low risk APL and treated according to the AIDA protocol - induction and 3 consolidation cycles - the patient achieved a complete molecular response in September 2013 and started maintenance therapy. On follow-up PML-RARA transcript remained negative. In January 2016 leukopenia and thrombocytopenia developed and a peripheral blood smear revealed hypogranular and agranular neutrophils. Immunophenotyping in the bone marrow aspirate identified undifferentiated blast cells that did not express cytoplasmic myeloperoxidase. The cytogenetic study showed normal karyotype. The molecular biology tests not identified PMLRARA transcript. A diagnosis of t-MDS (AREB-2 - WHO 2008) was established. Treatment of AML was started with 2 “3+7” regimens and 1 MEC cycle. Two months from diagnosis, while in CR, an allogeneic HSCT from an unrelated HLA compatible donor was performed after myeloablative regimen. An unfavorable clinical evolution was followed by death on day 9 after transplantation. The occurrence of t-MNs during CR of APL represents a particular problem in terms of follow-up and differential diagnosis of relapse and constitutes a dramatic complication for a disease with a favorable prognosis.

This work was supported by the grants PN 41-087 /PN2-099 from the Romanian Ministry of Research and Technology

Open access

Mariana Mihăilă, V. Herlea, Camelia Dobrea, Ioana Lupescu, Gina Rusu Munteanu, Grethi Chiriac, L. Micu, R. Serescu and I. Copaci

Abstract

We present the case of a 76 year old female patient admitted in the Department of Cardiology for physical asthenia, profuse sweating and dyspnea with orthopnea for about one month. Clinical and paraclinical assessments performed at admission confirmed the diagnosis of cardiac tamponade. Surgical intervention was performed and 400 mL of clear effusion were drained. Post-operative evolution was marked by recurrence of symptoms, requiring after 3 weeks a new drainage of 600 mL of clear effusion, and biopsy of the pericardium was performed. Pathological exam described serous pericarditis with chronic inflammatory infiltrate, xanthogranulomatous reaction intricated in the pericardium and mesothelial hyperplasia. The patient was subsequently transferred to the Department of Internal Medicine for further investigations. Physical examination showed a patient with altered general status, pallor, vesicular murmur absent in both bases, presenting cutaneous hyperpigmentation at the level of the right hemi-abdomen and hip with posterior extension, and a peripheral indurated erythematous plaque. The patient presented nodular masses of 3 cm in the right latero-cervical and bilateral axillary regions, non-adherent to the superficial structures, as well as adenopathic blocks in both inguinal regions. CT scan of the thorax and abdomen showed moderate bilateral pleuresia, minimal pericardial effusion (15 mm) and multiple adenopathies on both sides of the diaphragm. Skin biopsy was performed, as well as bone marrow aspirate and excision of a right axillary lymph node. Pathological exams and immunohistochemistry tests confirmed the diagnosis of Plasma Cells Castleman disease.

Open access

Ana-Maria Moldovianu, Anca Popp, Zsofia Varady, Alina Tanase, Alexandra Marculescu, Camelia Dobrea, Didona Vasilache, Cerasela Jardan, Radu Niculescu and Daniel Coriu

Abstract

The purpose of this work is to present the results of allogeneic stem cell transplantation as therapy for patients diagnosed with acquired aplastic anemia in the Department of Bone Marrow Transplantation of Fundeni Clinical Institute and to elaborate an algorithm of treatment in aplastic anemia starting with the observations obtained from our clinical practice and following the European treatment guidelines in this group of patients.

Aplastic Anemia (AA) is a rare hematological disease characterized by pancytopenia and a hypocellular bone marrow. The paradigm of bone marrow failure syndromes, aplastic anemia is a diagnosis of exclusion despite the precision of its diagnosis criteria. Although AA is not a malignant disease, but an autoimmune disorder, the grave consequences of pancytopenia and clonal transformation into acute leukemia make it a potentially fatal condition.

The management of AA patients is challenging and necessitates a very well established treatment plan from the diagnosis.

We present the treatment algorithm for AA patients with recommendations based on both recent guidelines in the field and on our experience treating AA patients with allogeneic stem cell transplant. Therapeutic procedure algorithm comprises different approaches for different patient populations, age categories and availability of immunosuppression therapy or different types of donors.

According to the recent EBMT recommendations the treatment of choice for young patients (younger than 40 years) who have a matched sibling donor is hematopoietic stem cell transplantation (HSCT). For those patients who don’t have a matched sibling donor or are not candidates for HSCT due to older age, the immunosuppression with ATG and cyclosporine is an efficient treatment. The supportive care has an important role and the patients with aplastic anemia should be managed by a multidisciplinary team. For patients older than 40 years, the choice between immunosuppressive therapy (IST) and upfront transplant with HLA identical sibling donor remains a key question. However, the standard approaches for this category of patients is front line immunosuppression with ATG and cyclosporine and if they become refractory to at least one course of IST the allogeneic stem cell transplant using fludarabine-based conditioning is the second-line treatment option.

In our institution there were eleven AA patients treated with allogeneic stem cell transplantation from 2009 till 2015. They were all young patients with age between 19 and 42 years old and all had severe acquired aplastic anemia with transfusion dependence. Six cases were transplanted from a matched sibling donor and five patients had undergone an unrelated matched donor transplant. The allogeneic HSCT procedure was done both as front line therapy in the case of three patients and as second treatment choice in the rest of eight patients. Four patients died, three of them due to transplant related toxicity and one patient experienced severe autoimmune reaction with transfusion inefficacy complicated with intracerebral haemorrhage at four months from transplant.

In our opinion the most challenging aspect in treating AA patients is choosing the best treatment option taking into account the patient age and performance status, the severity of the disease and the availability of a donor for allogeneic HSCT.

Although the treatment strategy must be individualized in every patient case, it is necessary to make a standardization of treatment procedures in AA and to follow the evidence based recommendations available in the management of this rare disease.

Open access

Radu-Daniel Pintilii, Daniel Peptenatu, Ana-Maria Ciobotaru, Sorin George Toma, Ana Maria Grigore, Cristian-Constantin Drăghici, Răzvan-Cătălin Dobrea, Adrian Gabriel Simion, Ion Andronache, Camelia Teodorescu and Daniel Constantin Diaconu

Abstract

Creative economies are at the heart of the knowledge-based economy. The main objectives of the study are to present the spatial design of the regional systems of creativity in Romania and to identify the evolutionary trends, by creating spatial models for key economic indicators, specific to such economic activities. This paper focuses on how creative economies are concentrated in the national network of settlements and how they differentiate in terms of regional profile. Consequently, a yearly nationwide database was created for 2000-2012, which includes four-digit creative economic activities, according to the Classification of National Economy Activities, for each administrative unit in Romania. The analyses, conducted for the same period, show a concentration of creative economies as a national polycentric network which includes the capital city and cities with over 300,000 inhabitants, as well as their structured territorial systems emerging around them, representing the local and regional polycentric networks. The analysis of the economic profiles highlights the growing share of creative economies in the national economy that tends to contribute more and more to the increase of the operational complexity of the local and regional economies.