OC-07 - Decoding risk for thromboembolic events in lymphoma patients.

INTRODUCTION: There are few prediction tools for estimating the risk of thrombosis but they are based on studies performed on hospitalized medical patients without cancer or on hospitalized neutropenic cancer patients without special consideration to lymphoma patients. AIM: Aim of our study was to determine incidence of thromboembolic (TE) events in patients with non Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL) and chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL) who were hospitalized to the lymphoma department in the Clinic of hematology, Clinical Center Serbia, Belgrade and Clinic of hematology, Clinical Center Kragujevac. Also, we assessed 2 predictive models (Padua and Khorana score) and create new model for the identification of lymphoma patients at risk for thromboembolism. MATERIALS AND METHODS: We reviewed all medical records of patients with with NHL, HL and CLL/SLL diagnosed and treated at two previously mentioned institution between January 2006 and December 2014. RESULTS: The study population included 1820 eligible lymphoma patients. Of all the patients included in the study, 99 (5.4%) developed at least one TE during a follow-up period of 3 months from the end of therapy. In the final multivariate analysis, the following variables were independently associated with risk of TE: previous VTE and/or arterial events, reduced mobility (ECOG 2-4), obesity (BMI >30 kg/m(2)), extranodal localization, mediastinum involvement, development of neutropenia during therapy and hemoglobin level less than 100g/L. Subsequently, we assigned points for the risk model based on the regression coefficients obtained from the final model and developed Thrombosis Lymphoma (ThroLy) score consisting of all significant variables from the multivariate analysis. The Throly score was arrived at by assigning 2 points for all parameters with an OR >5 in multivariate regression analyses (e.g., previous VTE and arterial events, mediastinum involvement, and BMI) and 1 point for rest all other significant variables. Finally, population were divided into 3 risk categories for TE based on the score from the risk model: low (score 0-1), intermediate (score 2-3) and high (score >3). High risk score had a positive predictive value (probability of TE in those designated high risk) of 65.2%. CONCLUSIONS: Significance of our investigation is development of score that help phisicians to recruit lymphoma patients at risk for development of thromboembolic complications. Also, we can say that our score is dynamic allowing us to change approach during different phase of therapy and is not limited to outpatient settings or with some complicated laboratory analysis.

Enhanced International Prognostic Index (NCCN-IPI), Charlson Comorbidity Index and absolute lymphocyte count as predictors for survival of elderly patients with diffuse large B cell lymphoma treated by immunochemotherapy.

Diffuse large B cell lymphoma (DLBCL) affects more commonly patients over 60 years. These patients have vast number of comorbidities which can modify survival as well as other clinical parameters. The aim of this study was to evaluate prognostic significance of the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI), absolute lymphocyte count (ALC), absolute monocyte count (AMC), lymphocyte-to-monocyte ratio (LMR) and comorbidities expressed with Charlson Comorbidity Index (CCI). A total of 182 DLBCL patients 60 years old and older were included, focusing on whole group and patients older than 70. All patients were treated with immunochemotherapy.Overall treatment response was achieved in 84.6% of patients. The NCCN-IPI was of highly prognostic value in the analyzed group (p<0.0001). Survival analysis showed that ALC>1.1x109/L, AMC≤0.59x109/L, and LMR>2.8 were associated with more favorable outcome (p=0.029, p=0.019, p=0.028, respectively). The patients with CCI≥2 had poorer outcome (p=0.008) compared to the patients with CCI 0-1. Multivariate analysis showed that among ALC, AMC, LMR, NCCN-IPI and CCI, the NCCN-IPI was the critical parameter that significantly affected survival (p<0.0001). Furthermore, comorbidities were also valuable independent factors which influenced survival (p=0.031) as well as the ALC (p=0.024). In elderly DLBCL patients, NCCN-IPI and ALC proved their prognostic validity, while poorer outcome could be expected in older patients with high CCI (≥2). Furthermore, mentioned prognostic parameters retained their prognostic value in the group of patients older than 70.

Orbital and ocular adnexal Mucosa-Associated Lymphoid Tissue (MALT) lymphomas: a single-center 10-year experience.

Orbital and ocular andexal Mucosa-Associated Lymphoid Tissue Lymphoma (MALT) or ocular adnexal MALT lymphoma (OAML) is the most common of all eye non-Hodgkin lymphomas. Autoimmune inflammatory disorders and chronic infections are important etiological factors and CD5 and CD43 (sialophorin) tumor markers are significant negative prognostic factors. Disease signs and symptoms can occur a long time before diagnosis. Varieties of treatment options are available. The aim of this retrospective analysis was to compare the efficiency of different treatment options and to investigate disease outcome. Twenty OAML patients, diagnosed in the Clinic of Hematology, Clinical Centre of Serbia, between 2003 and 2013, were enrolled. In most cases, OAML developed in the eighth decade with greater incidence in the male population. Median age was 67.5 years. The median period between the appearance of local signs and symptoms and diagnosis was 7 months. The dominant sign at presentation was swelling of involved tissue (40%). The most common was orbital involvement (55%). All patients had localized disease. Observed laboratory parameters on presentation showed low disease activity. Sialophorin prognostic significance was not registered. Our patients were initially treated differently but there was no significant difference in progression-free survival (PFS) due to initial treatment option (p = 0.2957). Median PFS was 22 months (3-89), and 5-year PFS was 60%. Median overall survival (OS) was 43 months (1-105) and 5-year OS 95%. Eight patients (40%) relapsed and one patient died due to non-hematological complications. In our experience, most modern induction treatment options appear to result in the same, favorable outcome.

Survivin expression in patients with newly diagnosed nodal diffuse large B cell lymphoma (DLBCL).

Survivin is one of the inhibitors of apoptosis proteins (IAP) that might play an important role in the pathogenesis of diffuse large B cell lymphoma (DLBCL). The present study was designed to investigate the clinical and prognostic significance of survivin expression in nodal DLBCL. We analyzed lymph node biopsy specimens obtained from 56 patients with newly diagnosed nodal DLBCL, treated with immunochemotherapy (R-CHOP). The expression of survivin was analyzed using the standard immunohistochemical method on formalin-fixed and routinely processed paraffin-embedded lymph node specimens and evaluated semiquantitatively as a percentage of tumor cells. Survivin immunoexpression (>45 % positive tumor cells) was found in 22 (39.28 %) and observed as cytoplasmic staining in 15 patients, or mixed (cytoplasmic and nuclear) staining in 7 patients. A significant difference in survivin immunoexpression was noticed between the GCB and the non-GCB subtypes of DLBCL (p = 0.031). However, survivin immunoexpression had no significant association with IPI, "bulky" disease, extranodal localization, hemoglobin, Ki-67 immunoexpression or other clinicopathological parameters. A univariate analysis showed that survivin positivity was an unfavorable factor for therapy response and a predictor of shorter survival in patients with DLBCL (p = 0.048 and p = 0.034, respectively). Patients with survivin overexpression experienced a relapse more often than patients without expression of this apoptotic protein (27.3 vs. 11.8 %), but this difference did not reach statistical significance (p = 0.131). The results of this study showed that disregulation of survivin expression had an important role in the determination of the course of the disease in patients with nodal DLBCL treated with R-CHOP. Therefore, survivin represents a potential target for therapeutic intervention in DLBCL.

Biological and clinical features of non-Hodgkin's lymphoma in the elderly.

PURPOSE: The incidence of non-Hodgkin's lymphomas (NHLs) in elderly people has increased in recent years because the world population is getting older. The aim of this study was to compare the biological and clinical features in patients diagnosed with NHLs younger and older than 65 years, and the possible influence of age on the choice of optimal therapeutic approach. METHODS: We retrospectively evaluated 193 patients with NHLs: 111 (68%) were <65 years and 82 (42%) ≥65 years. The following parameters were analysed: age, gender, clinical stage, International Prognostic Index (IPI), histological type, presence of B symptoms, disease localization, presence of bulky mass, Karnofsky performance status (PS), comorbidities, blood counts, liver and renal function and serum LDH. RESULTS: Elderly patients had statistically more frequent indolent NHLs (p=0.036), IPI 3 and 4 (p<0.0001), presence of comorbidities (p<0.001), and less frequent presence of bulky disease (p7equals;0.043). Response to therapy was different in the 2 age groups: 29% of patients ≥65 years achieved complete remission (CR) in contrast to 71% of patients <65 years (p<0.001). The most frequent cause of death was disease progression (PD) (86% of younger patients and 71% of elderly patients (p7equals;0.150). Older patients died more frequently because of comorbidities compared younger ones (21 and 107percnt;, respectively; p=0.250), and had more complications of therapy (8.1 and 47percnt;, respectively (p=0.320). Overall survival (OS) was shorter in older patients in all lymphoma types: indolent lymphoma (36 vs. 17 months), aggressive (22 vs. 20 months) and very aggressive (14 vs. 1 months). Multivariate analysis showed that parameters for shorter survival in the elderly were Karnofsky PS <60, increased serum LDH and treatment toxicity. CONCLUSION: In elderly NHLs patients, treatment response and survival are significantly poorer. Since older patients mostly died of PD, they should be treated with standard regimens and best supportive measures.

Intravascular large B-cell lymphoma of central nervous system - a report of two cases and literature review.

Intravascular large B-cell lymphoma (IVL) is a rare form of diffuse large B cell lymphoma (DBCL) frequently presenting with skin and/or central nervous system (CNS) involvement. IVL involves CNS in 75 - 85% of patients and neurological symptoms include sensory and motor deficits or neuropathies, meningoradiculitis, paresthesia, hypostenia, aphasia, dysarthria, hemiparesis, seizures, transient visual loss, vertigo and impaired cognitive function. Neuroimaging discloses CNS involvement only in half of patients with neurological symptoms because there are no pathognomonic neuroradiological findings for IVL; ischemic foci are the most common presentation pattern and therefore vasculitis is the most common differential diagnosis. According to all mentioned data, diagnosis of CNS IVL requires a histopathological confirmation. Brain biopsy is absolutely indicated in patients with progressive neurological deterioration with unclear abnormalities in cerebral MR imaging. A general policy is that patients with IVL should be considered to have disseminated disease and should be treated with systemic chemotherapy. In younger patients with unfavorable features the high-dose chemotherapy with autologous stem cell transplantation should be used. Nevertheless, the course of IVL is rapidly progressive and ultimately fatal.

Immunophenotypic profile and clinical characteristics in patients with advanced stage mantle cell lymphoma.

The objective of this study was to evaluate immunophenotypic profile along with clinical follow-up in patients with advanced stage mantle cell lymphoma (MCL), and their possible influence on overall survival (OS). Bone marrow (BM) cell and/or peripheral blood mononuclear cell flow cytometric analyses of the following antigens were performed: HLA-DR, CD19, CD20, CD22, CD23, CD25, CD10, SmIg, kappa, lambda, CD79b, CD38, FMC7, CD3, CD2, and CD5. There were 14 patients in IV CS, and 26 patients in CS V. All patients were treated with CHOP. Immunological markers showed a typical phenotype (CD5+ CD23-, Cyclin D1) in all cases. Pathohistological type of BM infiltration was predominantly diffuse (72.5%), and in remainder of patients, nodular. Comparison of patients with leukemic phase of MCL with CSIV (BM), has shown significantly higher expression of CD19, CD20, and CD23, followed by permanently negative expression of CD23. Patients with blastic variant of MCL had higher expression of CD23, compared to typical MCL (P < 0.001). Median OS was 20 months, and there were no significant OS-differences between CS IV and leukemic phase patients. Survival analyses showed that negative prognostic influence had high IPI (P < 0.01), presence of extranodal localization (P < 0.01), and diffuse type of BM involvement (P < 0.01). Using Cox regression according to OS, IPI had independent prognostic value (P < 0.001). Our results demonstrated that in the advanced MCL patients the most powerful prognostic factor was IPI, while extranodal localization and type of BM infiltration were of a limited value.

Primary extranodal lymphomas of gastrointestinal localizations: a single institution 5-yr experience.

This study is aimed at comparison of patients with extranodal lymphomas based on pathohistological findings differences (MALT vs non-MALT) as well as regarding gastric and non-gastric localization, and determining the significance of clinical-laboratory parameters with respect to therapeutic response and length of survival. A total of 56 patients with extranodal non-Hodgkin's lymphomas of the gastrointestinal tract were evaluated over a 5-yr period. Regarding the localization of the disease, the stomach was most frequently affected, 39 patients (70%); followed by small and large intestines, 17 patients. As for the pathohistological findings, MALT lymphoma accounted for 70%, DLBCL 25%, while other subtypes accounted for 5%. Patients' distribution was analyzed according to CS based on both Ann Arbor and Lugano systems; however, the difference obtained between the groups was not statistically significant in both staging types of patients. Statistically significant difference in patients' distribution was not found with respect to IPI index, bone marrow infiltration, anemia, hypoalbuminemia, or histological subtype and localization. Difference in survival between patients according to the pathohistological type was not statistically significant also according to the type of the affected gastrointestinal tract organ. Statistical significance of difference according to survival probability was obtained based on age (survival is longer in patients over 55 yr of age); according to CS and according to Ann Arbor and Lugano classifications (the patients with lower CS live significantly longer); according to IPI index (the survival is significantly longer in patients with lower probability: IPI-0,1, and 2), as well as patients free of bone marrow infiltration whose survival is also significantly longer.

Ki-67 proliferative marker in lymph node aspirates of patients with non-Hodgkin's lymphoma.

Proliferative activity of lymphoma cells was tested by immunocytochemical staining with Ki-67 monoclonal antibody in 63 aspirates of peripheral lymph nodes sampled from patients suffering from non-Hodgkin's lymphoma. Referring to the dominant cell population in nodal aspirates, a rising trend of Ki-67 proliferative marker was noted from the small cells (X = 13.20) and small cells with notched nucleus (X = 43.52) and large cells (X = 79.47) with histopathologic equivalents corresponding to aggressive lymphoma. Statistical testing of the difference in the Ki-67 proliferative marker against demographic and clinical-laboratory characteristics of the studied patients revealed the levels of significance for the performance status, bone marrow infiltration, and albumin serum value. Correlation of cytomorphological and immunocytochemical results was tested against International Prognostic Index (IPI). Statistically significant correlation of Ki-67 with cytomorphology and REAL-immunocytochemical classification of lymphoma was confirmed, but not with the IPI index. In order to determine the prognostic importance of Ki-67 marker, the patients were classified into those with low Ki-67 (<20% of proliferating cells), mean proliferation index Ki-67 (range 20-59%), and high proliferative index Ki-67 (positive in over 60% of lymphoma cells). Testing Ki-67 with survival we have found that the low proliferative index was associated with the longest survival, median about 36 mo; for proliferative marker values ranging between 20 and 59%, the median survival was 30.4 mo; and survival of patients with the high proliferative index was only 12.9 mo.

Predictive value of prognostic indices in patients with follicular lymphomas.

PURPOSE: The aim of this study was to compare which of three indices--International Prognostic Index (IPI), Italian Lymphoma Intergroup (ILI) index, Follicular Lymphoma adapted International Prognostic Index (FLIPI)--is the most useful in predicting outcome in follicular lymphoma (FL) patients and to identify other clinical and laboratory prognostic factors that influence survival. PATIENTS AND METHODS: Clinical and prognostic studies were carried out in 99 patients with FL. RESULTS: The distribution of patients in IPI risk groups was 44.4%, 19.2%, and 36.4% of cases classified as low, intermediate, and high risk. According to ILI, low-, intermediate-, and high-risk scores were present in 34.3%; 27.3%, and 38.4% of FL patients. After applying the FLIPI index, the patients were divided into three risk groups: low (21.2% of cases), intermediate (39.4%), and high (39.4%) of FL patients. Survival curves demonstrated a high significant difference for the low- and high-risk group according to IPI and FLIPI (log rank=91.13 and 82.17 respectively; p < 0.0001). Difference in overall survival (OS) and failure-free survival (FFS) among low-, intermediate-, and high-risk groups according to ILI was statistically significant (log rank test p < 0.0001). CONCLUSION: All three indices are important tools for prognostic evaluation of FL patients, as well as useful in identifying FL patients with poor outcome. IPI and FLIPI classify patients into two risk groups (low/intermediate- and high-risk groups) with significance difference in OS and FFS, but ILI is more reliable in stratifying patients in low-, intermediate-, and high-risk groups.

[Angioblastic lymphadenopathy--its course and prognosis]. / Angioimunoblastna limfadenopatija--tok i prognoza.

INTRODUCTION: In recent years important advances have been made in the understanding of angioimmunoblastic lymphadenopathy since substantial controversy has been related to the name, course, prognosis and therapy of the disease. It was first recognized in the Kil Classification as a low risk T-cell lymphoma [5], and omitted from the most widely used Working Formulation for clinical purposes. According to the criteria of REAL (Revised European American Lymphoma), classification angioimmunoblastic lymphadenopathy (AILD) is one of peripheral postthymic T cell lymphomas that are an immunologically defined category of non-Hodgkin's lymphomas originating from the peripheral lymphatic tissues. Morphologically, AILD is characterized by partially or completely obliterated sinuses and frequent infiltration of the pericapsular tissue and substantial proliferation of epithelioid, postcapillary venules. Cytologically, polymorphous cellular infiltration with immunoblasts, transformed lymphoid cells, polyclonal plasma cells, eosinophils and epithelioid cells are found. Clinically, rapid occurrence of systemic symptoms in elderly individuals (sixth and seventh decades of life) with generalized lymphadenopathy, hepatosplenomegaly and cutaneous maculo-papulous or erythematous rash is noted. The patients are characterized with hyperimmune condition in the form of Coombs' positive haemolytic anaemia, polyclonal hypergamma-globulinaemia and liability to infections [8, 9]. In spite of numerous suggestions, therapeutic consensus has not been achieved, and the reported survival ranges from 1 to 30 months [10, 11]. Therefore, this information suggests an aggressive form of the disease with the 60% mortality rate. METHODS: At the Institute of Haematology of the Clinical Centre of Serbia in Belgrade in the last five years, from 1993 through August 1998, nine patients were diagnosed with AILD according to the results of pathohistological examination of the extirpated peripheral lymph nodes and the correlation with clinical picture and relevant laboratory findings. RESULTS: Clinical characteristics of nine patients in whom AILD was diagnosed after lymph node biopsy are given in Table 1. The group consisted of 6 men and 3 women, mean age 53. Eight patients were in advanced stage of the disease at the time of the diagnosis (III and IC CS), while the patient in II CS stage had a large tumorous mass (M+). All patients had initial systemic symptoms. Five of them developed fever with chills. Three patients had evidence of extranodal infiltration of the bone marrow. Infiltration of the liver was suspected in two patients according to aberrant hepatogram values, although pathohistological verification was not obtained. In one patient lung infiltration was histologically verified in addition to bone marrow and liver infiltration. All patients had peripheral lymphadenopathy, and most of them hepatosplenomegaly, as well. Three patients had the so called bulky form of the disease since the diameter of the largest tumour exceeded 10 cm. On admission, most were in poor overall condition, and only two were apparently healthy. Knowing that AILD is basically an immunoregulatory disease and that the described cases of association with systemic diseases of the connective tissue and some drugs were implied in the triggering of AILD, Table 2 shows important information obtained form histories of these patients. Namely, 7 of 9 patients had cutaneous changes suggestive of erythematous or maculopapular rash, while three had received corticosteroid therapy for months before AILD was diagnosed since toxoallergic exanthema had been incorrectly suspected. Three patients received gold sodium thiosulfate therapy for rheumatoid arthritis, while four had history of allergy to drugs and pollen. Table 3 shows laboratory results: anaemia was present in 8 of 9 patients, it was severe in three with haemoglobin values of 67 g/L, 72 g/L and 50 g/L, respectively. Five patients had haemolysis. A

[Treatment of aggressive non-Hodgkin's lymphoma with the ProMACE- CytaBOM protocol]. / Lecenje agresivnih neHockinskih limfoma protokolom ProMACE CytaBOM.

INTRODUCTION: The Working Formulation Classification (for clinical use) divides non-Hodgkin's lymphoma (NHL), according to the nature of the disease and response to therapy into the low, medium and high risk lymphomas. Although these subgroups include different pathohistological types of NHL, they are considered sufficiently homogenous for joint therapy planning [1]. The first generation protocol (CHOP) managed to achieve complete remission (CR) in 50-55% of patients with 30-35% of survival rate [2]. A large four-branch comparative study of SWOG group compared CHOP as the first generation protocol with the third generation protocols ProMACE CytaBOM, m-BACOD and MCOD-D. The results have shown a similar CR and survival rates, so that CHOP is considered a gold standard for the treatment of aggressive NHL [6]. In the light of individual reports stating a high CR rate in the treatment of aggressive NHL by ProMACE CytaBOM [3-5] we present our experience and observations related to the use of this protocol. METHOD: Over the period from 1991 through May 1996 at the Department of Lymphoproliferative Diseases, Institute of Haematology, Clinical Centre of Serbia in Belgrade, we treated 25 patients with pathohistologic evidence of medium to high risk lymphomas, where cases of lymphoblast lymphoma and Burkit's lymphoma were excluded. The median follow-up was 27 months (maximum 63 months). RESULTS: Four of 25 patients were > 60 years. Three of these died. Pathohistological analysis revealed that of 20 cases of medium risk aggressive lymphoma five had diffuse, small cleaved cells, 7 had diffuse mixed and 8 diffuse centroblast cells. Although diffuse NHL with small cleaved cells is classified into clinically indolent lymphomas, two of five patients were in the fourth clinical stage, and three of five patients had a large tumorous mass. In the high risk group five patients had immunoblast lymphoma. Karnofsky index was high in 20/25. According to Ann Arbor criteria 19/25 patients were in IVCS and 7/25 had a large tumour mass. Most patients had clinical symptoms (21/25). Extranodal localization was confirmed in 19 patients. Bone marrow and hepatic infiltrations were most common: 9 and 6 patients, respectively. Eleven patients had a single extranodal localization, while 8 had 2 or more. The median follow-up was 27 months (maximum 63 months), and 21/25 (84%) patients responded to therapy (CR + PR). Complete remission was achieved in 14 patients (56%), and PR in 7 (28%) patients. In the CR group two died, and relapse developed in one after 28 months. In 11 cases CR is maintained. The average duration of CR was 16 months (3-38 months), and PR was maintained for 6 months (20 months in one case). The average survival was 24.5 months (range 3-53). DISCUSSION: The fact that a half of adult patients with disseminated aggressive NHL can be cured with combined chemotherapy is the major oncological achievement in the last 20 years. The protocol combines 4-8 drugs, and the joint report of the SFOG group for lymphoma in over 1200 patients with lymphoma has shown that the second and third generation protocols are not more effective than the standard CHOP or CHOPBleom protocols [6]. The optimum therapeutic protocol in the treatment of aggressive lymphoma is still unpredictable due to the fact that it is inadequate to compare the results of individual institutions with the results of collaborative groups; there is also a significant difference in the prognostic factors in different research groups; there is no sufficient complete and published results that suggest the lower CR than the original reports (which may be related to the evaluation of tumour and remission). There are not sufficient data on the incidence of secondary carcinoma and leukaemia [1]. The decision on the therapy should be based on two lines of information: those related to each particular patient (age, associated diseases) and those related to the tumour (large mass, immunophenotyping, cytoge

Solitary intracranial plasmacytomas.

We present two cases of an unusal localised extramedullary plasmacytoma with a long survival period: a 42-year-old woman with left temporal and a 25-year-old woman with left parietal intracranial plasmacytoma. The tumor masses were totally removed in both patients and their histological, histochemical (PAS and methyl green pyronin positive granules) and immunohistochemical (positive light chains mostly lambda, and negative stains for GFAP, NSE and S-100 protein) properties showed that the tumor tissues consisted of monoclonal population of plasma cells. Our cases were diagnosed as solitary cerebral plasmacytomas since the presence-of underlying multiple myeloma has been ruled out by the clinical, laboratory, radiographic and immunological investigations. Postoperatively the patients were given 40 Gy to the whole cranium and additional 20 Gy focused on the tumor site. Complete remissions were achived 7.5 and 5.5 years, respectively.

[Non-Hodgkin's lymphoma of the thyroid gland--2 case reports]. / Nehockinski limfomi stitaste zlezde--prikaz dve bolesnice.

The authors present two female patients with Non-Hodgkin's lymphoma of the thyroid gland. The first had Non-Hodgkin's lymphoma, follicular, diffuse of centrocytic cells (FCC-intermediate grade risk), and the second had an immunoblastic Non-Hodgkin's lymphoma with large cells (high grade risk). After "staging" procedures, it was estimated that the first patient was in I EA and the second in II EB clinical stage. They were treated by surgical removal of involved tissue, combined chemotherapy and local radiotherapy. A complete remission was achieved in both patients without signs of recidivation for 8 months in one patient and 18 months in the second subject, after treatment. The elder patients more often manifest this type of lymphoma, especially if they already had chronic thyroiditis of Hashimoto's type. Using the combined, contemporary treatment, the overall five-years survival is about 56 +/- 7 percent.

Acute megakaryoblastic leukaemia with mediastinal tumor.

Acute megakaryoblastic leukemia (AMKL) is a rare myeloproliferative syndrome with a fulminant clinical course characterized by progressive pancytopenia, pallor, weakness and severe hemorrhage. We present a 18-year old male with pancytopenia and massive hemorrhage, lymphadenopathy, organomegaly, and with unusual presentation of retrocardial mediastinal tumor on the right side. The diagnosis of AMKL was established by combining cytological and immunocytochemical analyses of peripheral blood cells (blasts were GPIIIa and GPIb positive); by immunohistochemical analysis of lymph node (dysplastic megakaryocytes were GPIIIa and F VIII positive); in vitro culture studies confirmed enormous growth of CFU-Mk with high proliferative capacity. In spite of therapy, the patient died 3 months after the first signs of the disease.

The reevaluation of the ferric thiocyanate assay for lipid hydroperoxides with special considerations of the mechanistic aspects of the response.

The mechanistic aspects of the spectrophotometric method of analysis of lipid hydroperoxides (LOOH) based on the oxidation of ferrous to ferric ion and subsequent complexation of the latter by thiocyanate are considered. The method of analysis, as revised by us, was carried out in the same solvent that had been used for the extraction of lipids from the sample, a deoxygenated chloroform:methanol or a dichloromethane:methanol (2:1, v/v) mixture, and used a single solution containing both reagents, Fe2+ and SCN-, for developing the response. In that solvent, total lipids up to 5 mg/ml did not interfere, and linear increase of the absorbance of ferric thiocyanate complex was obtained up to 2 x 10(-5) M LOOH. Molar absorptivity of the ferric thiocyanate complex expressed per mol of LOOH was determined as 58,440 M-1 cm-1, based on the average of four ferric ions produced by each LOOH molecule. The estimated lowest detectable limit was about 170 pmol LOOH/ml of analyzed solution, which corresponded to about 50 mumol LOOH/kg lipid in complex natural mixtures. In addition to good sensitivity, and in contrast to some other more popular spectrophotometric assays for LOOH, the method is responsive also to hydroperoxides of mono- and di-unsaturated fatty acids. The method, thus, provides an easy, rapid, sensitive, and complete measure of hydroperoxidation of lipids.

Angioimmunoblastic lymphadenopathy (AILD) with benign course.

A group of rare systematic lymphoproliferative disorders have been described under the heading of angioimmunoblastic lymphadenopathy with dysproteinaemia (AILD), from purely reactive to bona fide malignancies. Some patients exhibit a benign form of disease, but most exhibit an aggressive form with high mortality rate. We present two elderly patients with prominent constitutional symptoms, generalized lymphadenopathy, hepatosplenomegaly, diffuse maculopapular rash, polyclonal hypergammaglobulinaemia and immunohaemolytic anaemia. Lymph node biopsies showed features consistent with the diagnosis of AILD. The patients were treated with steroid and they are in complete remission 3.5 and 2.5 years, respectively after the diagnosis has been established.

[Acute megakarioblastic leukemia: de novo and transformation of chronic myeloid leukemia]. / Prikaz bolesnika s akutnom megakarioblastnom leukemijom.

Acute megakarioblastic leukemia (AMKL) is a rare myeloproliferative syndrome with a fulminant clinical course characterized by progressive pancytopenia, palior, weakness and severe haemorrhage. Two cases of AMKL are presented: a 18-year old male with pancytopenia and massive haemorrhage, lymphadenopathy, organomegaly and mediastinal tumour. The diagnosis of AMKL was established by cytological and immunocytochemical analyses of peripherial blood cells (blasts were GPIIIa and GPIb postitive), by histological analysis or the bone marrow and lymph node, and immunohistochemical analysis of lymph node. The second case had megakarioblastic transformation of HGL which was confirmed by cytomorphological and immunophenotypical analyses. In spite of therapy, the patients died soon after the first signs of the disease.

[Treatment of non-Hodgkin's lymphomas of medium and high malignancy]. / Lecenje neHockinski limfoma srednjeg visokog stepena maligniteta.

Comparison of therapeutical protocols of three generation: CHOP the first, COP-BLAM and ProMACE-MOPP the second and ProMACE-Cyta BOM the third, was based on treatment od 45 patients with agressive lymphoma in whom these protocols were applies as the primary chemotherapy. In our series of patients and therapeutical conditions the CHOP protocol proves somewhat superior to the second and third generation protocols: persentige of complete remission (CR) was high (64%), mean duration of CR was among longes (12 months), while neither cases of relapse during the monitoring of patients were noted not toxic effects of therapy. The rate of fatal outcomes was among the lowest (36%) and the probability of surviving longer then 16 months was the highest (9.73).