First-Line Therapy for Nodal T-cell Non-Hodgkin Lymphomas: an Unmet Need in Hematology.

PURPOSEOF REVIEW: The main aim of this review is to summarize first-line therapy of nodal T-cell non-Hodgkin lymphoma. RECENT FINDINGS: Current treatment with CHOP chemotherapy results in poor outcomes in the majority of patients. However, there are advances within the field. First breakthrough is the ECHELON-2 trial which showed that the addition of brentuximab vedotin improves outcomes in anaplastic large cell lymphoma. However, other types of peripheral T-cell non-Hodgkin lymphoma were underrepresented with optimal treatment not known. Second breakthrough is an increase of autologous stem cell transplantation usage in the first complete metabolic remission, except in ALK + anaplastic large cell lymphoma, offering better disease control. Despite advances in the field, CHOP remains the standard treatment for the majority of these lymphomas, but multiple trials are underway with the aim to improve this unmet need in hematology and, hopefully, leading us to a new era in the treatment of peripheral T-cell lymphomas.

The prognostic value of red blood cell characteristics on diabetic retinopathy development and progression in type 2 diabetes mellitus.

BACKGROUNDAlthough it is considered that the pathogenesis of diabetic retinopathy (DR) in type 2 diabetes mellitus (T2DM) is primarily due to chronic hyperglycemia resulting in vascular changes and retinal ischemia, the red blood cells (RBCs) disorders might also represent an important pathophysiological risk factor.OBJECTIVETo evaluate whether the RBC properties contribute to DR development and progression in T2DM.METHODSThis prospective observational study comprised 247 persons with T2DM free of DR or with non proliferative DR without any signs of anaemia. The patients were reacessed after 60-months.RESULTSThe mean age of our study population was 56 years, 54.9% males with diabetes duration of 11,18±1,28 years. During the follow up, 16 (5.84%) participants developed non proliferative DR and 9 (3.64%) progressed to PDR while the mean corpuscular volume (MCV) and red cell distribution width (RDW) MCV rose. Both MCV and RDW correlated positively with HbA1c (r = 0,468, p = 0.003 and r = 0.521, p < 0.001), while Cox regression analysis revealed that besides age, diabetes duration, HbA1c, hypertension and dyslipidemia presence, MCV and RDW are also associated with the risk of DR development and progression (HR 1.057 and 1.237, p < 0.001).CONCLUSIONSWe clearly demonstrated that RBC's characteristics might represent a risk factor for DR development and progression.

[GUIDELINES FOR DIAGNOSIS AND TREATMENT OF PATIENTS WITH MYELODYSPLASTIC SYNDROME].

Myelodysplastic syndrome Working Group of the Croatian Cooperative Group for Hematologic Diseases (CROHEM), Referral center of the Ministry of Health of the Republic of Croatia for diagnostics and treatment of MDS, as well as the Croatian Society for Haematology of the Croatian Medical Association have made Croatian guidelines for diagnosis and treatment of myelodysplastic syndrome (MDS). MDS is a heterogeneous group of clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis, dysplasia, cytopenia and risk of transformation to acute myeloid leukemia (AML). Diagnosis is based on morphological characteristics of hematopoietic cells supplemented with the cytogenetic analysis and bone marrow flow cytometry. Due to great differences in the natural course of the disease, i.e. time to progression to AML and the expected time of survival several scoring systems have been developed to determine the disease risk. The treatment of patients with MDS is based on the risk factors of the disease as well as the individual risk of treatment.

[FOLLOW-UP OF PATIENTS WITH CLASSICAL HODGIN LYMPHOMA AFTER TREATMENT--NOVEL EVIDENCE AND DILEMMAS. LITERATURE REVIEW]. / PRACENJE BOLESNIKA S KLASICNIM HODGKINOVIM LIMFOMOM NAKON LIJECENJA--SUVREMENA SAZNANJA I NEDOUMICE. PREGLED LITERATURE.

In this review we present current evidence for the follow-up of patients treated for classical Hodgkin lymphoma (HL). Nowadays introduction of novel therapies enabled successful treatment in most patients with classical HL in first remission with 5-year overall survival rate estimation of 80%. We have performed extensive literature search on the methodological approach to detection of relapse. Evidence regarding imaging clinical methods in detecting relapse on serial computed tomography and/or positron emission tomography scans is scarce. These imaging modalities are associated with considerable economic cost, unnecessary exposure to radiation and patients' stress. Furthermore, the detection of asymptomatic relapse does not seem to be associated with improved outcome in this patient group. Available data on this subject indicate that standard imaging methods, such as ultrasound, and judicious clinical examination in detecting of relapse should be the basis of HL patient follow-up. Late toxicity due to various modalities of treatment represents serious morbidity in HL. They vary from secondary solid cancers and hematologic neoplasms, associated with poor outcome, to benign disorders (fertility issues, thyroid dysfunction, cardiovascular and lung disorders). Current data on the incidence, prevalence and etiological factors do not yet provide evidence on appropriate screening methods. Most recommendations in various guidelines are associated with low level of evidence (grade IV). We, therefore, propose individually-tailored screening methods for each patient based on the modality of treatment received.

[CURRENT APPROACH TO NON-HODGKIN MANTLE CELL LYMPHOMA: LITERATURE REVIEW].

Mantle cell lymphoma (MCL) represents the fourth most common type of non-Hodgkin lymphomas. It is characterized by aggressive course and frequent relapses. The main aim of this review is to evaluate current treatment approach towards this type of lymphoma. In younger patients the chemotherapy including high doses of cytarabine is the gold standard. In case of complete or partial remission, the consolidation with autologous stem cell transplantation is indicated as consolidation approach. In older patients CHOP-R regimen is not the treatment of choice. These patients should be treated with bendamustine in combination with rituximab. In case of complete or partial remission, further therapy with rituximab maintenance as consolidation represents an option. The vast majority of patients with MCL will ultimately relapse which poses a challenge in treatment approach. The approach in relapsed MCL can be divided in two types: chemotherapy or biologic therapy. In young fit patients chemotherapy based on bendamustine and cytarabine is a reasonable option. In patients with comorbidities or poor performance status biologic agents are reasonable options. Ibrutinib, Bruton kinase inhibitor, is characterized by highest overall response rate and the longest duration of response and should be offered to these patients. With the development of novel potent inhibitor of B cell receptor signaling pathway, these agents may become the gold standard in future and introduce the treatment of MCL in "chemo-free"era.

[AUTOLOGOUS STEM CELL TRANSPLANTATION IN REFRACTORY OR RELAPSED DIFFUSE LARGE B CELL LYMPHOMA - A SINGLE CENTRE EXPERIENCE]. / AUTOLOGNA TRANSPLANTACIJA PERIFERNIH MATICNIH STANICA U REFRAKTORNOM ILI RELAPSNOM NE-HODGKINOVU LIMFOMU DIFUZNOGA B-VELIKOSTANICNOG TIPA - ISKUSTVO JEDNOG CENTRA.

Autologous stem cell transplantation represents the gold standard in chemosensitive diffuse B large cell lymphoma in relapse or in refractory setting. The aim of this study was to present the outcome of peripheral autologous stem cell transplantation in patients with refractory or relapsed diffuse large B cell lymphoma. We retrospectively analysed the data of 62 patients, who underwent this procedure for the period 2000-2013. The majority of patients (71%) were treated with miniBEAM salvage chemotherapy and all received BEAM myeloablative protocol followed by the stem cell reinfusion. The overall response rate for autologous transplantation was 75.8%. Median overall survival was 37.2 months. Median event-free survival was 16.9 months. Factors associated with overall survival were state of disease prior to salvage chemotherapy, chemosensitivity of disease, International prognostic index, disease activity at the relapse, response to autologous transplantation and post-transplantation radiotherapy. The use of rituximab was not significantly correlated to the outcome. In this patient group autologous stem cell transplantation was found to be effective in achieving remission and survival showing the adequate role of this procedure in this clinical setting. We stress out that autologous stem cell transplantation was effective in 32.5% patients with chemorefractory disease after salvage therapy.

[Diagnostic approach and treatment of immune thrombocytopenia in adults]. / Dijagnosticki pristup i lijecenje imune trombocitopenije u odrasloj dobi.

The aim of this review is to provide the Croatian medical public with novel insights into the definition, pathogenesis, diagnostic algorithms and treatment approaches to immune thrombocytopenia (ITP) in adults. Recently, primary ITP has been uniformly defined as an autoimmune disorder characterized by an isolated platelet count lower than 100 x 10(9)/L without preexisting disease or conditions, which could lead to thrombocytopenia. The recognition of primary and secondary ITP is important because they require different treatment strategies. In secondary ITP, therapeutic approach oriented towards the underlying disorder. Unlike childhood onset ITP, which is a self-limited condition with high rates of spontaneous remissions, adulthood onset ITP usually has chronic course. Previously, the pathogenesis of ITP was considered to be immune mediated destruction of platelets in liver and spleen, while recent findings have shown a novel pathophysiological pathway based on the inhibition of thrombopoiesis, leading to novel treatment approaches. The diagnosis of ITP is based on exclusion of the possible underlying causes of thrombocytopenia and consists of simple diagnostic procedures. The decision to treat ITP should be based individually: platelets count (lower than 30 x 10(9)/L), various bleeding risk factors and patient's preference. The use of corticosteroids is the mainstay of first line therapy. Two most commonly used corticosteroids are prednisone and dexamethasone. Prednisone is administered continuously, while dexamethasone is applied in cycles. Due to the lack of randomized clinical trials, it is not possible to recommend certain class of corticosteroid therapy. Another two agents used as first line therapy in case of corticosteroid refractoriness or the need of rapid platelet elevation, are intravenous immunoglobulins and anti-D immunoglobulin (anti-D is not approved in Europe). They are characterized by rapid onset of platelet recovery and low long-term remission rates. Until recently, splenectomy, with adequate infectious and thromboprophylaxis, was the therapy of choice in patients who did not respond to corticosteroids due to high long-term remission rates and low relapse rates. This procedure can be offered to a younger patient without significant comorbidities after the first year of ITP duration. With advances in the understanding of ITP pathogenesis, a new class of drug has been established: thrombopoietin agonists (TPO). Eltrombopag and romiplostim, the TPO agonists currently approved for the management of ITP in patients who failed the first line therapy and are not suitable for splenectomy, are only two agents that have shown benefits in large clinical randomized trials. They are characterized by a high response rate and appropriate safety profile, but the need for continuous use, a high relapse rate after therapy withdrawal, and price limit their use in everyday practice. TPO agonists represent an appropriate treatment choice in patients who have relapse after splenectomy. Another agent, often used in everyday clinical practice, is rituximab with high response and relapse rates. Its use is based on small studies, and due to the lack of clinical randomized controlled trials, rituximab is not approved by the leading medical agencies for this indication. As shown in this review article, our understanding and therapy for ITP has improved, but further research is needed to implement evidence-based therapy in clinical practice.

[Wounds in hematology patients]. / Rane kod hematoloskih bolesnika.

Hematology patients can have wounds as part of the initial presentation of the disease, as a result of infection or therapy.Wound therapy is very important and requires multidisciplinary approach of the hematologist, surgeon, dermatologist, and all other medical staff involved in the patient's care. It is very important to provide aseptic care and prevent infections that could complicate the patient's recovery and cure. It is very important to recognize the wound with malignant infiltration because an appropriate chemotherapy can be curative.

[Post-transplant lymphoproliferative disease in liver transplant recipients--Merkur University Hospital single center experience]. / Post-transplantacijska limfoproliferativna bolest u bolesnika s transplantacijom jetre - iskustvo KB Merkur.

Post-transplant lymphoproliferative disorder (PTLD) is an increasingly recognized condition as the number of solid organ and bone marrow transplant recipients increases. It can be a life threatening fulminant disorder and affects approximately 8% of solid organ transplant recipients. Epstein-Barr virus (EBV) is closely involved in the pathogenesis of PTLD and the majority of PTLD cases arise in response to primary infection with EBV or to re-activation of previously acquired EBV. The principal risk factors underlying the development of PTLD are the degree of overall immunosuppression and EBV serostatus of the recipient. The most commonly used pathologic classification of PTLD is the World Health Organization classification, which divides PTLD into three categories: early lesions, polymorphic PTLD, and monomorphic PTLD. Early lesions are characterized by reactive plasmacytic hyperplasia. Polymorphic PTLD may be either polyclonal or monoclonal and is characterized by destruction of the underlying lymphoid architecture, necrosis, and nuclear atypia. In monomorphic PTLD, the majority of cases (>80%) arise from B cells, similar to non-Hodgkin's lymphoma in immunocompetent hosts. The most common subtype is diffuse large B-cell lymphoma, but Burkitt's/Burkitt's-like lymphoma and plasma cell myeloma are also seen. Rarely T-cell variants occur, which include peripheral T-cell lymphomas and, rarely, other uncommon types, including gamma/delta T-cell lymphoma and T-natural killer (NK) cell varieties. Hodgkin's disease-like lymphoma is very unusual. An accurate diagnosis of PTLD requires a high index of suspicion, since the disorder may present subtly and/or extranodally. Radiologic evidence of a mass or the presence of elevated serum markers (such as increased LDH levels) are suggestive of PTLD, with positive finding on ultrasonography, computed tomography, magnetic resonance and/or positron emission tomography scanning (possibly indicating metabolically active areas) also favoring the diagnosis. The management of PTLD poses a major therapeutic challenge and although there is reasonable agreement about the overall principles of treatment, there is still considerable controversy about the optimal treatment of individual patients. EBV-related PTLDs are a significant cause of mortality in patients undergoing orthotopic liver transplantation with the observed mortality rate of up to 50%. This paper presents the experience acquired at Merkur University Hospital in the diagnosis and treatment of patients with liver transplantation and PTLD.

[Fine needle aspirate of lymph node as the analytical sample for immunophenotyping]. / Punktat limfnog cvora kao analiticki uzorak za fenotipizaciju stanica.

In modern clinical laboratory routine, cell analysis by flow cytometry means help in setting up the diagnosis by determination of B-lymphocyte clonality and thus separation of benign and malignant lymphoproliferative diseases. The aim of this study was to assess the value of cytologic diagnosis and adequacy of the material obtained by fine needle aspiration (FNA) of lymph nodes for flow cytometry analysis in cases of benign lesions and primary malignant lesions of lymph nodes. In addition, the aim was to determine B-lymphocyte clonality in different groups of benign and malignant lymph node lesions. The study was based on medical documentation, cytologic smears of FNA lymph node samples and results of flow cytometry immunophenotyping. A total of 239 patients were included over a one-year period. Patients were classified according to cytologic findings in the groups of non-Hodgkin's lymphoma of B cell origin (55%), benign lymphoproliferative disease (22%), undefined group of monomorphic population of lymphatic cells (16%), and the rest in the group of non-Hodgkin's non B cell origin. Study results showed FNA to be an appropriate method for obtaining sufficient numbers of cells for analysis by flow cytometry because there was no inadequate samples in our study group. In some cases of monomorphic lymphoid cell population, cytologic diagnosis was limited to small cell lymphomas, so determining the clonality by flow cytometry is crucial in separating malignant from benign lymphoproliferative disease. It is concluded that FNA associated with the flow cytometry method is a simple and safe method in the diagnosis of lymphoproliferative disease.

[Extramedullary multiple myeloma of the colon--case presentation and literature review]. / Ekstramedularna infiltracija kolona u bolesnika s multiplim mijelomom--prikaz bolesnika i pregled literature.

Multiple myeloma with gastrointestinal infiltration is rare, and it has been usually described in some case reports or case series. Stomach and small intestine are mostly involved, while large bowell involvement is very rare. Multiple myeloma should be considered in the differential diagnosis of some other diseases of the large bowel associated with weight loss, diarrhoea, malabsorption, frequent lumbar pain, effort intolerance. Colonoscopic biopsy followed by histopathological examination is essential for the diagnosis of multiple myeloma. Multiple myeloma with extramedullary infiltration of the colon has no well defined treatment guideline. Localised infiltration of gastrointestinal tract could be treated by surgical resection, but as these tumors are radiosensitive, radiotherapy has also been used. Chemotherapy with pulsed dexamethasone and afterwards a combination of cyclophosphamide, vincristine, melphalan and prednisone has been described in some case studies. Some patients were treated with other therapies incuding thalidomide, bortezomib, autologous or allogeneic stem cell transplantation. The clinical presentation, diagnosis and therapy may be challenging, so we present a 66-year old patient with extramedullary multiple myeloma of the colon who was treated at our Department.

[Multiple myeloma in a patient with chronic lymphocytic leukemia--case report and literature review]. / Multipli mijelom u bolesnika s dugogodisnjom kronicnom limfocitnom leukemijom--prikaz bolesnika i pregled literature.

The occurrence of B-cell chronic lymphocytic leukemia (B-CLL) and another B-cell neoplasm in the same patient is a rare event and is mostly described in the literature as single case reports. In most cases reported in the literature, CLL was diagnosed several years before multiple myeloma. Some patients were only observed for CLL without therapy, whereas others had already been treated for CLL when the diagnosis of myeloma was established. Some authors came to a conclusion that therapy used for treating CLL can induce some secondary neoplasms, like multiple myeloma. We present a male patient who was diagnosed with multiple myeloma 11 years after B-CLL had been diagnosed. Two hematologic neoplasms in one patient could be a diagnostic problem, but also a therapeutic challenge.

[Billateral pleural effusion as first manifestation of multiple myeloma]. / Bilateralni pleuralni izljev kao prva manifestacija multiplog mijeloma.

Multiple myeloma is clonal malignancy of plasma cells with overproduction of monoclonal antibodies and destruction of bones. Hypercalcemia, anemia and renal disfunction are common manifestations of the disease. Billateral pleural effusion is rare multiple myeloma presentation with unfavorable prognosis so it is important to recognizze it for better diagnostic and therapy approach. 59-year old woman was admitted to Hematology Department with history of severe caugh, dyspnea and left chest pain. Physical examination and chest X-ray showed billateral pleural effusion while cytologic examination of pleural aspirate found plasma cells. Bone marrow examination and skeleton X-ray confirmed diagnosis of multiple myeloma. Serum and urine immunoelectrophoresis detected lambda Bence Jones protein. This case is rare manifestation of multiple myeloma.

Serum immunoglobulins in non-Hodgkin's lymphoma patients.

Serum proteins and immunoglobulin (Ig) findings in 119 non-Hodgkin's lymphoma (NHL) patients were analysed. Out of them 96 (81%) patients had B non-Hodgkin lymphoma (B-NHL), and 23 (19%) T-NHL. Indolent type of NHL was more frequent (77 patients, 65%), then aggressive type of NHL (42 patients, 35%). Most patients had normal serum protein concentration, the increased protein concentration was seen in 17% of patients while decreased concentration was noticed in 7% of patients. Hypoalbuminaemia was more frequent (43%) then hyperalbuminaemia (1%). In contrast to albumin, low levels of other protein fractions (alpha1-, alpha2-, and beta-globulin) were rather rare (0.6%, 4%, and 3% of patients, respectively) and high levels were frequent (23%, 37%, and 8%, respectively). Polyclonal hyperimmunoglobulinaemia was more frequent finding than hypoimmunoglobulinaemia. In 29% patients higher IgG level and in 25% patients higher IgA level were found. IgM hypoimmunoglobulinaemia (22%) was more frequent than IgG (11%) and IgA (8%) hypoimmunoglobulinaemia. M-spike in serum protein electrophoresis was found in 11 (7%) patients. The statistically significant association was not found between serum Ig concentration and lymphoma malignancy grade as well as between serum Ig concentration and immunologic origin of lymphoma. T-NHL patients have more often IgA concentration level above or under normal values than B-NHL patients (p < 0.05).

Lenalidomide induced good clinical response in a patient with multiple relapsed and refractory Hodgkin's lymphoma.

BACKGROUND: A 24-year-old female patient was diagnosed with classic Hodgkin's lymphoma in clinical stage II, and combination chemotherapy followed by radiotherapy was initiated. During the following 5 years, the disease progressed despite several standard therapeutic approaches, including autologous and allogeneic stem cell transplantation. METHODS: Lenalidomide (25 mg daily) treatment was then initiated in a continuous dosing schedule. Positron emission tomography scans were performed before and during lenalidomide treatment. Hematologic and laboratory values, as well as physical condition were also assessed before and during lenalidomide treatment. RESULTS: Four months after continuous lenalidomide treatment, tumor load was significantly reduced, B symptoms had resolved, and the patient's physical condition had improved, allowing her to resume normal daily-living activities. Evaluations after 15 months of lenalidomide treatment indicated limited disease progression. Nevertheless, the patient was feeling well and maintaining a normal active life. Treatment was well tolerated, allowing the patient to remain on continuous dosing, which has now been maintained for 18 months. CONCLUSION: Daily, long-term lenalidomide treatment provided clinical benefit and was well tolerated in a patient with relapsed, advanced classic Hodgkin's lymphoma.

Serum levels of VEGF and bFGF in hypoxic patients with exacerbated COPD.

Hypoxia frequently complicates the course of chronic obstructive pulmonary disease (COPD). Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are the two most potent angiogenic factors and may play a role in adaptation to hypoxia. The aims of the study were to assess the serum levels of VEGF and bFGF and to evaluate their mutual relationship in hypoxic patients with exacerbated COPD. The study group consisted of 50 hypoxic (PaO(2) 53 mmHg) patients with exacerbated COPD. Control groups were 30 stable COPD patients with PaO(2) 70 mmHg, and 30 healthy blood donors. The serum concentrations of VEGF and bFGF were measured using commercial enzyme-linked immunoassay kits. Patients with exacerbated COPD had significantly higher serum VEGF levels (1,089.16 +/- 1,128.03 pg/mL) compared to those with stable COPD (197.68 +/- 178.06 pg/mL) (p < 0.0001) and healthy blood donor group (257.69 +/- 170.4 pg/mL) (p < 0.0001). Serum bFGF levels were significantly higher in the exacerbated COPD group (6.15 +/- 2.56 pg/mL) compared to control groups (p = 0.0001). Basic FGF was undetectable in the stable COPD and blood donor groups. Since VEGF and bFGF correlated significantly with the majority of factors investigated in COPD patients, multivariate analysis was performed. According to the step-wise regression analysis, VEGF was best determined by PaO(2), WBC and IL-6. Basic FGF was best determined by PaO(2) and pH. The highly significant, simple correlation between VEGF and bFGF was lost in multivariate analysis. This suggests that their correlation is not independent, but due to factors that remain in the model after step-wise regression. These are essentially linked to the level of hypoxia. Results of our study suggest that VEGF and bFGF production is stimulated in hypoxic patients with exacerbated COPD. Elevated levels of VEGF and bFGF may activate the process of neoangiogenesis, which may lead to increased perfusion and an improvement in tissue oxygenation in this group of patients.

Value of fine-needle aspiration cytology in diagnosis of Hodgkin's lymphoma and anaplastic large cell lymphoma: one centre experience.

The aim of the study was to determine the value and limitations of cytology in diagnosis of Hodgkin's lymphoma (HL) and anaplastic large cell lymphoma (ALCL) as well as differentiation between these two entities. We analysed the FNA cytodiagnoses and histopathological reports, as well as treatment and survival in 89 newly diagnosed consecutive patients with these lymphomas treated in our clinical department. These patients (40 male, 49 female; age range 16-93 years; 44 in clinical stages I-II; 38 with B symptoms) were diagnosed and treated during a period of 64 months (1.1. 2004-1.5.2009). The FNA cytodiagnoses were available in 86 patients and the pathohistological diagnoses were available in 84 patients. Cytology revealed 65 classic HL, 18 ALCL and three patients in which diagnosis was not informative. Among 65 FNA cytodiagnoses of HL, comparison with histopathology was made in 61 cases and the histopathological diagnoses were as follows: 56 (91.8%) HL; three ALCL; one diffuse large B cell lymphoma and one marginal zone B cell lymphoma. In the group of 18 FNA cytodiagnoses of ALCL eight patients (53.3%) had definitive diagnosis of ALCL (either as T-cell or O type), five (33.3%) of HL and in three cases a histopathological diagnosis could not be made. These results confirm the value of FNA in diagnostic procedure in patients with HL and ALCL, especially in HL group of patients. Since we have an almost uniform group of patients according to therapeutic approach, we did univariate analyses and found out that patients with FNA cytodiagnoses of HL, younger than 55 years, with early stage of the disease and without B symptoms had significantly longer overall survival (OS). FNA cytodiagnosis has clinical relevance in differentiation between HL and ALCL.

T-lymphoblastic lymphoma with an unusual t(8;14)(q24;q11)--case report.

Cytogenetic abnormalities seen at presentation of acute lymphoblastic leukemia or lymphoblastic lymphoma (ALL/ LBL) are associated with distinct clinical and hematologic disease entities. T-ALL/LBL are morphologically indistinguishable from those of B-ALL/LBL. An abnormal kariotype is found in 50-70% of cases of T-ALL/LBL. We present a 35-year old male patient with T-ALL/LBL and t(8;14)(q24;q11.2). Our patient presented with B-symptoms, bulky mediastinal disease and CNS infiltration. Bone marrow was morphologically normal and cytogenetically without clonal aberrations. Cytological findings of the supraclavicular lymph node showed numerous CD3 positive (100%) and CD2 positive (88%) lymphoblasts, negative for CD34 and CD10. Flow cytometry of lymph node revealed T cell phenotype of immature cells: CD45+CD2+CD5+CD7+CD4+CD8+CD3cyt +CD3TdT+CD10-CD34-HLAD/DR-. Cytogenetic analysis of lymph node showed translocation t(1;4)(p32;p12), t(8;14)(q24;q11.2). Southern blot analysis of extracted DNA from the supraclavicular lymph node demonstrated clonal rearrangement of the T cell antigen receptor (TCR/J) gene (region Vb+Jb2). Based on these findings, diagnosis of T lymphoblastic non Hodgkin lymphoma was established. Cerebrospinal fluid analysis showed CNS infiltration with 49% lymphoblasts positive for CD4 and CD8. The disease progressed rapidly with poor response to therapy. T-ALL/LBL with an unusual t(8;14)(q24;q11.2) is a very rare hematologic disorder with rapid disease progression and poor response to conventional therapy because of frequent central nervous system involvement and early relapses.

New parameters of diploid histogram of image DNA cytometry and newly characterized types of nucleolar organizer region structures in defining the proliferative-kinetic index in chronic leukemic lymphoproliferative disorders.

OBJECTIVE: To introduce new parameters of diploid histogram of image DNA cytometry and new types of silver-stained nucleolar organizer regions (AgNORs) and to validate resulting proliferative-kinetic index (PKI) in a prognostic study of patients with chronic leukemic lymphoproliferative disorders (CLLPD). STUDY DESIGN: A total of 413 smears of from various tumor mass compartments-bone marrow, peripheral blood and lymph node-were analyzed in CLLPD as a whole, as well as separately in the B-chronic lymphocytic leukemia with variants (B-CLL+V). The analysis of the diploid histogram included percentage of cells at the peak of the DNA histogram and percentage of cells with lower and higher contents of DNA than cells at the peak. The new types of AgNORs were described as homogeneous, inhomogeneous and annular. RESULTS: The newly introduced parameters of DNA and AgNOR are significant predictors of survival. Based on the most representative AgNOR and DNA characteristics related to survival, the PKI score was calculated. The CLLPD and B-CLL+V patients had a statistically significantly better prognosis when PKI was < 4. CONCLUSION: PKIs have confirmed the hypothesis that different prognostic subgroups could be identified within the homogeneous groups of neoplasms with relatively low malignancy (CLLPD and B-CLL+V).

[The disappearance of CD20 positive lymphocytes in the pleural effusion after intrapleural application of rituximab]. / Nestanak CD20 pozitivnih limfocita iz pleuralnog izljeva nakon intrapleuralne primjene rituksimaba u bolesnice s folikularnim limfomom.

A 63 year old woman with non-Hodgkin lymphoma presented with unilateral pleural effusion, which when aspirated revealed CD19 and CD20 positive malignant cells. Prior to this, the patient had received several lines of chemotherapy (CHOP, VAD, FED) with no effect on pleural effusion. Repeated percutaneous drainage procedures were unable to control the effusion either. Rituximab was therefore instilled in a dose escalating manner via repeated pleurocenteses. Fifty days after the application of rituximab, pleural effusion was still present but reduced in size. Flow cytometry and immunocytochemistry performed on the same day showed CD19 positive cells which were lacking CD20 epitope, which could be explained by either engagement or destruction of the CD20 epitope upon interaction with rituximab making the detection of the CD20 molecule impossible by routine flow cytometry. What is especially interesting is the fact that even 50 days after the application of rituximab intrapleurally no new CD20 positive cells could be found in the pleural effusion by immunochemistry or flow cytometry, opening an interesting issue concerning the length of rituximab's activity when applied locally. Although our patient had no adverse effects, further analysis of rituximab's activity and safety when applied intrapleurally is warranted.