Revealing a Phenotypical Appearance of Ibrutinib Resistance in Patients With Chronic Lymphocytic Leukaemia by Flow Cytometry.

Background: Ibrutinib is widely known as an effective and well-tolerated therapeutical choice of the chronic lymphocytic leukaemia (CLL). However, acquired resistance may occur during the treatment, causing relapse. Early detection of ibrutinib resistance is an important issue, therefore we aimed to find phenotypic markers on CLL cells the expression of which may correlate with the appearance of ibrutinib resistance. Methods: We examined 28 patients' peripheral blood (PB) samples (treatment naïve, ibrutinib sensitive, clinically ibrutinib resistant). The surface markers' expression (CD27, CD69, CD86, CD184, CD185) were measured by flow cytometry. Furthermore, the BTKC481S resistance mutation was assessed by digital droplet PCR. Moreover, the CLL cells' phenotype of a patient with acquired ibrutinib resistance was observed during the ibrutinib treatment. Results: The expression of CD27 (p = 0.030) and CD86 (p = 0.031) became higher in the clinically resistant cohort than in the ibrutinib sensitive cohort. Besides, we found that high CD86 and CD27 expressions were accompanied by BTKC481S mutation. Our prospective study showed that the increase of the expression of CD27, CD69 and CD86 was noticed ahead of the clinical resistance with 3 months. Conclusion: Our study suggests that the changes of the expression of these markers could indicate ibrutinib resistance and the examination of these phenotypic changes may become a part of the patients' follow-up in the future.

Morphologic and molecular analysis of Richter syndrome in chronic lymphocytic leukaemia patients treated with ibrutinib or venetoclax.

Richter syndrome (RS) represents the development of high-grade lymphoma in patients with chronic lymphocytic leukaemia (CLL) or small lymphocytic lymphoma (SLL) and presents a diagnostic and therapeutic challenge with an adverse prognosis. The genetic background and morphology of RS in CLL patients treated with chemoimmunotherapy is extensively characterised; however, our knowledge about RS in patients treated with targeted oral therapies should be extended. To understand the morphologic and molecular changes leading to RS in CLL patients treated with the Bruton's tyrosine kinase inhibitor, ibrutinib, and the BCL2 inhibitor, venetoclax, sequential samples from six CLL/SLL patients undergoing RS were collected in both the CLL and RS phases. A detailed immunophenotypic analysis of formalin-fixed, paraffin-embedded tissue specimens of RS phase was performed, followed by extensive molecular characterisation of CLL and RS samples, including the immunoglobulin heavy chain gene (IGH) rearrangement, TP53 mutations, drug-induced resistance mutations in BTK and BCL2 genes and various copy number changes and point mutations detectable with multiplex ligation-dependent probe amplification (MLPA). Rare, non-diffuse large B-cell lymphoma phenotypes of RS were observed in 3/6 cases, including plasmablastic lymphoma and a transitory entity between diffuse large B-cell lymphoma and classical Hodgkin lymphoma. The majority of cases were clonally related and harboured an unmutated variable region of the immunoglobulin heavy chain gene. Abnormalities affecting the TP53 gene occurred in all patients, and every patient carried at least one genetic abnormality conferring susceptibility to RS. In the background of RS, 2/5 patients treated with ibrutinib showed a BTK C481S resistance mutation. One patient developed a BCL2 G101V mutation leading to venetoclax resistance and RS. In conclusion, our findings contribute to better understanding of RS pathogenesis in the era of targeted oral therapies. Rare phenotypic variants of RS do occur under the treatment of ibrutinib or venetoclax, and genetic factors leading to RS are similar to those identified in patients treated with chemoimmunotherapy. To our best knowledge, we have reported the first BCL2 G101V mutation in an RS patient treated with venetoclax.

Distinct miRNA Expression Signatures of Primary and Secondary Central Nervous System Lymphomas.

Central nervous system (CNS) lymphoma is a rare and aggressive non-Hodgkin lymphoma that might arise in the CNS (primary CNS lymphoma) or disseminates from a systemic lymphoma to the CNS (secondary CNS lymphoma). Dysregulated expression of miRNAs is associated with various pathologic processes, and miRNA expression patterns may have diagnostic, prognostic, and therapeutic implications. However, miRNA expression is understudied in CNS lymphomas. We performed expression analysis of 798 miRNAs in 73 CNS lymphoma samples using the NanoString platform, followed by an analysis to identify potential diagnostic biomarkers characterizing subgroups and to examine differences based on their primary and secondary nature, molecular subtype, mutational patterns, and survival. Thirty-one differentially expressed miRNAs were identified between primary and secondary groups. In addition, 7 more miRNAs were identified associated with a molecular subtype and 25 associated with mutation status. Using unsupervised clustering methods, a small but distinct primary CNS lymphoma subgroup, with characteristically different expression patterns compared with the rest of the cases was defined. Finally, differentially regulated pathways were identified in the above comparisons and the utility of miRNA expression patterns in predicting survival was assessed. Our study identifies a novel CNS lymphoma subgroup defined by distinct miRNAs, proves the importance of specific miRNAs and pathways in the pathogenesis of CNS lymphomas, and provides the basis for future research in defining potential biomarkers.

Beneficial Effect of Lenalidomide-Dexamethason Treatment in Relapsed/Refractory Multiple Myeloma Patients: Results of Real-Life Data From 11 Hungarian Centers.

In Hungary, the cost of lenalidomide-based therapy is covered only for relapsed multiple myeloma (MM) patients, therefore lenalidomide is typically used in the second-line either as part of a triplet with proteasome inhibitors or as a doublet. Lenalidomide-dexamethasone is a standard treatment approach for relapsed/refractory MM, and according to recent large randomized clinical trials (RCT, the standard arm of POLLUX, ASPIRE, TOURMALINE), the progression-free survival (PFS) is expected to be approximately 18 months. We surveyed ten Hungarian centers treating MM and collected data of 278 patients treated predominantly after 2016. The median age was 65 years, and patients were distributed roughly equally over the 3 international staging system groups, but patients with high risk cytogenetics were underrepresented. 15.8% of the patients reached complete response, 21.6% very good partial response, 40.6% partial response, 10.8% stable disease, and 2.5% progressed on treatment. The median PFS was unexpectedly long, 24 months, however only 9 months in those with high risk cytogenetics. We found interesting differences between centers regarding corticosteroid type (prednisolone, methylprednisolone or dexamethasone) and dosing, and also regarding the choice of anticoagulation, but the outcome of the various centers were not different. Although the higher equivalent steroid dose resulted in more complete responses, the median PFS of those having lower corticosteroid dose and methylprednisolone were not inferior compared to the ones with higher dose dexamethasone. On multivariate analysis high risk cytogenetics and the number of prior lines remained significant independent prognostic factors regarding PFS (p < 0.001 and p = 0.005). Our results show that in well-selected patients Lenalidomide-dexamethasone can be a very effective treatment with real-world results that may even outperform those reported in the recent RCTs. This real world information may be more valuable than outdated RCT data when treatment options are discussed with patients.

Molecular Subtypes and Genomic Profile of Primary Central Nervous System Lymphoma.

Primary central nervous system lymphomas (PCNSL) are aggressive non-Hodgkin lymphomas affecting the central nervous system (CNS). Although immunophenotyping studies suggested an uniform activated B-cell (ABC) origin, more recently a spectrum of ABC and germinal center B-cell (GC) cases has been proposed, with the molecular subtypes of PCNSL still being a matter of debate. With the emergence of novel therapies demonstrating different efficacy between the ABC and GC patient groups, precise assignment of molecular subtype is becoming indispensable. To determine the molecular subtype of 77 PCNSL and 17 secondary CNS lymphoma patients, we used the NanoString Lymphoma Subtyping Test (LST), a gene expression-based assay representing a more accurate technique of subtyping compared with standard immunohistochemical (IHC) algorithms. Mutational landscapes of 14 target genes were determined using ultra-deep next-generation sequencing. Using the LST-assay, a significantly lower proportion (80% vs 95%) of PCNSL cases displayed ABC phenotype compared with the IHC-based characterization. The most frequently mutated genes included MYD88, PIM1, and KMT2D. In summary, we successfully applied the LST-assay for molecular classification of PCNSL, reporting higher proportion of cases with GC phenotype compared with IHC analyses, leading to a more precise patient stratification potentially applicable in the diagnostic algorithm of PCNSL.

Real World Efficacy and Safety Results of Ixazomib Lenalidomide and Dexamethasone Combination in Relapsed/Refractory Multiple Myeloma: Data Collected from the Hungarian Ixazomib Named Patient Program.

Ixazomib-Revlimid-Dexamethasone is an all-oral treatment protocol for multiple myeloma with a manageable tolerability profile which was available through a named patient program for Hungarian patients from December 2015 to April 2017. We analyzed the clinical characteristics and survival of 77 patients treated at 7 centers within this program. The majority of patients responded, we found complete response in 9, very good partial response in 8, partial response in 32, minor response or stable disease in 13 and progressive disease in 11 patients. Progression free survival was 11.4 months. There was a trend of longer progression free survival in those with 1 vs. >1 prior treatment, with equally good effectivity in standard risk and high risk cytogenetic groups. The adverse events were usually mild, none leading to permanent drug interruptions. There were 5 fatalities: 3 infections and 2 pulmonary embolisms. Our real word data support the use of Ixazomib-Revlimid-Dexamethasone as a highly effective and well tolerated oral treatment protocol for relapsed myeloma.

Discrepancy Between Low Levels of mTOR Activity and High Levels of P-S6 in Primary Central Nervous System Lymphoma May Be Explained by PAS Domain-Containing Serine/Threonine-Protein Kinase-Mediated Phosphorylation.

The primary aim of this study was to determine mTOR-pathway activity in primary central nervous system lymphoma (PCNSL), which could be a potential target for therapy. After demonstrating that p-S6 positivity largely exceeded mTOR activity, we aimed to identify other pathways that may lead to S6 phosphorylation. We measured mTOR activity with immunohistochemistry for p-mTOR and its downstream effectors p(T389)-p70S6K1, p-S6, and p-4E-BP1 in 31 cases of PCNSL and 51 cases of systemic diffuse large B-cell lymphoma (DLBCL) and evaluated alternative S6 phosphorylation pathways with p-RSK, p(T229)-p70S6K1, and PASK antibodies. Finally, we examined the impact of PASK inhibition on S6 phosphorylation on BHD1 cell line. mTOR-pathway activity was significantly less frequent in PCNSL compared with DLBCL. p-S6 positivity was related to mTOR-pathway in DLBCL, but not in PCNSL. Among the other kinases potentially responsible for S6 phosphorylation, PASK proved to be positive in all cases of PCNSL and DLBCL. Inhibition of PASK resulted in reduced expression of p-S6 in BHD1-cells. This is the first study demonstrating an mTOR independent p-S6 activity in PCNSL and that PASK may contribute to the phosphorylation of S6. Our findings also suggest a potential role of PASK in the pathomechanism of PCNSL and in DLBCL.

Effects of nociceptin and nocistatin on uterine contraction.

The presence and effects of nociceptin (N/OFQ) and nocistatin (NST) in the central nervous system have been reasonably well described, but less data are available on their peripheral functions. Besides their presence in several peripheral organs (white blood cells, airway, liver, skin, vascular and intestinal smooth muscles, ovary, and testis), they have been found in the pregnant myometrium in both rat and human. The level of their precursor prepronociceptin is elevated in the preterm human myometrium as compared with full-term samples, whereas it gradually increases toward term in the pregnant rat uterus. Both N/OFQ and NST inhibit myometrial contractions, an effect which can be enhanced by naloxone and blocked by Ca²âº-dependent K⁺ channel (BK(Ca)) inhibitors. Both compounds increase the myometrial cAMP level which may be responsible for the activation of this channel and subsequent intracellular hyperpolarization. NST releases calcitonin gene-related peptide from the sensory nerve ends, which explains its cAMP-elevating effect. In contrast with the nervous system, where they behave as antagonists, N/OFQ and NST are able to potentiate the uterine-relaxing effect of each other in both rat and human tissues. Further studies are required to clarify the roles of N/OFQ and NST in the regulation of the myometrial contractions and the perception of pain during delivery.

Nocistatin inhibits pregnant rat uterine contractions in vitro: roles of calcitonin gene-related peptide and calcium-dependent potassium channel.

The endogenous neuropeptide nociceptin/orphanin FQ, translated from the prepronociceptin gene, exerts a contraction-inhibitory effect on the rat uterus. As nocistatin has been reported to cause functional antagonism of the pro-nociceptive effects of nociceptin, we set out to investigate its effects on the pregnant rat uterus and to elucidate its signalling pathway. The expression of prepronociceptin mRNA in the uterus and nocistatin levels in the uterus and the plasma were confirmed by RT-PCR and radioimmunoassay. The uterine levels of prepronociceptin mRNA and nocistatin were significantly increased by the last day of pregnancy, while the plasma nocistatin levels remained unchanged. In the isolated organ bath studies nocistatin inhibited the prostaglandin- and the KCl-evoked contractions in the uterus dose-dependently. This latter effect was decreased by preincubation with capsaicin. Incubation with calcitonin gene-related peptide after capsaicin treatment caused an elevation in the contraction-inhibitory effect of nocistatin. The effect of nocistatin was also decreased by the Ca(2+)-dependent K(+) channel inhibitor paxilline, against spontaneous uterine contractions. Nociceptin potentiated the action of nocistatin. Naloxone decreased the effect of nocistatin administered either alone or in combination with nociceptin. In Ca(2+)-poor environment, this effect of naloxone was suspended. Enzyme immunoassay for the uterine intracellular cAMP levels partially confirmed the results of in vitro contractility studies. We conclude that nocistatin, generated locally in the uterus, exerts an inhibitory effect, the mechanism being mediated in part by Ca(2+)-dependent K(+) channels, the elevation of cAMP levels and sensory neuropeptides.

[Burkitt's lymphoma presenting as ovarian tumor]. / Ovariumtumor formájában jelentkezo Burkitt-lymphoma.

Burkitt's lymphoma is a rapidly progressing tumor, which could be cured in 60-80% of cases. Its infiltration of the ileo-cecal region often spreads to the ovaries, though primary ovarian manifestation is also common. By presenting our case of a 27-year-old nulliparous patient with primary ovarian Burkitt's lymphoma, we would like to draw attention to its diagnostic and therapeutic difficulties.

[Standard CHOP immuno-chemotherapy for primary mediastinal lymphomas]. / A primer mediastinalis lymphomák standard R-CHOP immun-kemoterápiás kezelése.

INTRODUCTION: Primary mediastinal lymphoma (PMBCL) is an aggressive diffuse large B-cell lymphoma entity. It is a rare disease with specific clinical symptoms. The tumor is predominantly localized in the mediastinum but grows rapidly and infiltrates the surrounding tissues and organs. Two thirds of the patients are young females. Previous studies showed that third generation treatments are more effective than former standard cyclophosphamide-doxorubicin-vincristine-prednisolone (CHOP) regimens. AIM: Authors' goal was to assess whether adding the anti-CD20 monoclonal antibody, rituximab to the standard CHOP regimen improves the efficacy of the treatment compared to their previous results with CHOP and third generation chemotherapy regimens. METHODS: Between October, 2002 and December, 2004 they have started the rituximab-CHOP (R-CHOP) treatment of 20 newly diagnosed, previously untreated PMBCL patients. Results were compared to the data of 24 patients receiving CHOP (n = 9) or procarbazin-prednisolone-doxorubicin-cyclophosphamide-etoposide-cytosin-arabinoside-bleomycin-vincristin-methotrexate (ProMACE-CytaBOM) (n = 15) treatment in the past. RESULTS: During an average follow-up of 64.6 months, the 5-year overall survival (OS) rate was significantly higher in the R-CHOP group compared to the CHOP treatment (79.4% vs. 33.3%; p = 0.026). However, due to the low number of cases, significant statistical difference could not be demonstrated in the 5-year event-free survival (EFS: 70.0% vs. 33.3%; p>0.05), disease-free survival (DFS: 70.0% vs. 33.3%; p>0.05) and relapse-free survival rate (RFS: 93.0% vs. 100%; p> 0.05), despite of the remarkable numeric difference. When comparing the 5-year survival rates of R-CHOP and ProMACE-CytaBOM treatments, the results were very similar without any significant statistical difference between the two types of treatment (OS: 79.4% vs. 80%; EFS: 70.0% vs. 60.0%; DFS: 70.0% vs. 60.0%; RFS: 93.0% vs. 82.0%; p> 0.05 in all cases). With adding rituximab to CHOP treatment, which was previously considered an insufficient treatment on its own, authors have obtained as good results in treating PMBCL as with third generation regimens. Patients have received the R-CHOP treatments without major side effects and mainly as out-patients. CONCLUSIONS: Standard R-CHOP treatment could therefore replace the more toxic third generation regimens in PMBCL as well. The data are comparable with those reported in the international literature.

[Prognostic value of FDG-PET in Hodgkin lymphoma for posttreatment evaluation. Long-term follow-up results]. / Az FDG-PET prognosztikai értéke Hodgkin-lymphomás betegek követésében - hosszú távú eredményeink.

UNLABELLED: In the past few decades Hodgkin lymphoma (HL) has become a highly curable malignant disease, as a result of using modern polychemotherapy and irradiation. Differentiation of active tumor from fibrosis or necrosis within residual radiographic masses represents a problem of interpretation. AIMS: The aim of this retrospective study is to assess the value of FDG-PET for prediction of remission or relapse in HL. PATIENTS AND METHODS: Data of 128 patients, who had residual masses on CT after completion of their planned treatment, have been analyzed. FDG-PET was performed between January 1995 and February 2005. RESULTS: The median duration of the follow-up from PET was 75.5 months (range: 20-180 months). 89 (70%) patients had negative and 39 (30%) patients had positive FDG-PET results. The numbers of true-positive, true-negative, false-positive and false-negative subjects were 29, 83, 10 and 6, respectively. Sensitivity of post-treatment FDG-PET was 83%, specificity 93%, positive predictive value 74%, negative predictive value 93%, and accuracy 88%. The difference between the event free survival of PET positive and negative cases is highly significant (p = 0.0000), according to the Mantel-Cox test. CONCLUSION: Our results, in accordance with literature, clearly indicate that patients with negative FDG-PET results are unlikely to progress or relapse during a long follow-up. However, false positive uptake is a problem. We have investigated the effect of age, histological subtype, clinical stage and the type of treatment on the accuracy, but on the basis of these facts we could not find any significant difference. However, the date of the investigation influenced the results: before 2000 the number of false results was significantly higher than after that time, which shows the importance of investigators' experience.

[Results of immuno-chemotherapeutic treatment of patients with diffuse large B-cell lymphoma]. / Diffúz nagy B-sejtes lymphomák immunokemoterápiás kezelésével elért eredményeink.

Treatment with cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP) has been considered as the standard therapy for diffuse large B-cell lymphoma (DLBCL) for more than 20 years. CHOP treatment in combination with targeted immunotherapy, rituximab (R-CHOP), resulted in significant improvements in the treatment of this group of patients. In this study, efficacy of R-CHOP and R-CHOP-like treatments was analysed. Results were compared to the data of historical patients only receiving CHOP treatment or CHOP-like treatment. Between September 2002 and April 2005, 140 newly diagnosed, untreated DLBCL patients started to receive R-CHOP treatment in a single centre. The eligibility criteria included advanced stage (clinical stages III-IV), or large tumour size (>7 cm) and/or symptom B or extranodal manifestation in the case of clinical stages I-II. The results were compared to the data of 130 patients only receiving CHOP treatment in the past. In the patients receiving R-CHOP, the therapeutic outcomes were superior for all parameters. During an average follow-up period of 44 or 52 months, the overall remission rate was 73.6% in the R-CHOP group in comparison with 47.7% in the CHOP group. The 5-year overall survival was 68.6% vs. 41.0% (RR: 0.4293, CI: 0.2963-0.6221; p < 0.0001), the event-free survival was 59.8% vs. 33.5% (RR: 0.5038, CI: 0.3606-0.7038; p < 0.0001) and the progression-free survival was 64.4% vs. 37.6% (RR: 0.4915, CI: 0.3442-0.7019; p < 0.0001). Since prognostic parameters were more favourable in the R-CHOP group, patient groups were also compared using the International Prognostic Index score. Again, significant differences were revealed by the subgroup analyses. The 5-year overall survival was 74.4% vs. 47.9% (RR: 0.4475, CI: 0.2418-0.8285; p = 0.0084) and 52.0% vs. 28.8% (RR: 0.4989, CI: 0.3098-0.8035; p = 0.003) in the group with good prognosis and in the group with poor prognosis, respectively. In the group with very good prognosis, the statistical difference between the two groups in terms of the 5-year survival parameters remained undetectable as a result of the already very high therapeutic effect and low case number (OS and EFS: CHOP: 100% and 62.5% vs. R-CHOP: 90.9% and 87.0%; p = 0.3873 and p = 0.1702). Combining the standard CHOP treatment with rituximab resulted in a significant improvement of the therapeutic outcomes irrespective of the prognostic grouping. The data are comparable with those reported in the international literature.

[Hodgkin's lymphoma in adolescents: where to treat it--in an adult or pediatric institution?]. / Hodgkin-lymphoma adolescens korban. Hol érdemes kezelni: felnôtt- vagy gyermekintézményben?

UNLABELLED: Adolescent patients with Hodgkin's lymphoma (HL) are treated either in pediatric, or in adult oncological wards. AIM: The aim of our work was to compare the treatment modalities and the survival rates in adolescents with HL treated in adult (A) or pediatric (P) institutes. METHODS: From January 1990 to December 2004, 138 patients (14-21 years) with HL were treated in two adult institutes (A) and 107 in the 10 centres of the Hungarian Pediatric Oncology Network (P). RESULTS: Male:female ratio was 1:1.15 (A) and 1:1.38 (P). The mean age was 18.6 (A) and 15.7 (P) years. There was no difference between the distribution of the stages in the two patient groups. The distribution of histological subtypes (A and P): nodular sclerosing 47% and 59%, mixed cellularity 45% and 25%, lymphocyte rich 1.5% and 10%, lymphocyte depleted 4% and 1%, nodular lymphocyte predominant 1.5% and 3% and unknown 1% and 2%. The majority of the patients were treated with ABVD (A) and OPPA/OEPA +/- COPP (P). One hundred and fifteen (A) and 97 (P) adolescents received irradiation therapy. 80% (A) and 91% (A) of the patients got radiotherapy. In group A 14%, in group P 13% of the patients had relapse. In group A 16 patients died and in group P 7. There was no significant difference in the overall survival (OS) rates at 5 and 10 years in the two patient groups. The event-free survival (EFS) was 76.5 +/- 4% and 72.5 +/- 4% at 5 and 10 years in group A, and 85.3 +/- 4% at both times in group P ( p = 0.0452). CONCLUSION: Survival rates in HL are quite high, 80-90% of the patients can be cured. Event-free survival was higher in pediatric than in adult institutes. In case of patients younger than 18 years, the survival rates were much better in pediatric institutes, so these patients should be treated in pediatric institutes or with protocols used by the pediatricians.

[Treatment of primary mediastinal large B-cell lymphomas]. / Primer mediasztinalis nagy B-sejtes lymphomák kezelése.

INTRODUCTION: Primary mediastinal large B-cell non-Hodgkin's lymphoma is a relatively rare disease with specific clinical symptoms. This tumour originates from a subset of B-cells of the thymus and at the time of the diagnosis the disease is predominantly localised in the mediastinum. The tumor grows rapidly and frequently involves other thoracic structures. The majority of the patients are young females. There are no histologic features that reliably distinguish these tumors from other diffuse large B-cell lymphomas. This is the only lymphoma subtype which can only be defined by the combination of clinical and pathologic features. Analysis with DNA microarrays verified that primary mediastinal and diffuse large B-cell lymphomas are different diseases. AIMS: Comparing the effectiveness of two types of anthracycline-based standard chemotherapy regimens and the evaluation of the prognostic markers which are applied in large B-cell lymphomas. METHODS: 27 patients with primary mediastinal lymphoma were treated by the authors with anthracycline-based polychemotherapy with complementary radiotherapy from January 1995 to December 2002. RESULTS: Complete remission was obtained in 15 patients (56%) and no relapse was observed in this group. 9 additional patients (33%) achieved partial remission, while in 3 cases (11%) the treatment was ineffective. The patients who failed to achieve complete remission were subsequently treated with more intensive chemotherapy. Afterwards, those patients who were chemosensitive, underwent high-dose chemotherapy with autologous peripheral blood stem-cell transplantation. The chemoresistant patients received palliative chemotherapy. The 5-year overall survival rate of the 27 patients was 62.11%. CONCLUSION: The authors found that the procarbazine, prednisolone, adriamycin, cyclophosphamide, etoposide, cytosine-arabinoside, bleomycin, vincristine, methotrexate treatment was more effective than the cyclophosphamide, adriamycin, vincristine, prednisolone combination. The expected 5-year overall survival rates were 83.57% vs. 33.33%, respectively. This difference was significant (p = 0.017). No prognostic value of age adjusted international prognostic index, LDH- and b2-microglobulin levels were found. The results with the new standard of combined immuno-chemotherapy (rituximab--cyclophosphamide, adriamycin, vincristine, prednisolone) seem to be hopeful and more effective than earlier treatments.

[The role of PET scan in the investigation of the lymphatic spreading of Hodgkin's disease]. / A PET szerepe a Hodgkin-kór nyirokterjedésének vizsgálatában.

The authors investigated the role of PET, as a non-invasive diagnostic method, in the analysis of lymphatic spreading of Hodgkin's disease (HD). Whole-body FDG scans were carried out in 71 patients along with [11C]-methionine examinations, if necessitated by inconclusive FDG results. Based on these findings involvement-frequencies were calculated for each lymphatic region. The three most frequently involved lymphatic regions were the mediastinum (83.1%), the left cervical and left supraclavicular regions (78.9%) and the right cervical and right supraclavicular regions (76.1%). These data support the hypothesis that HD originates from the cervical or supraclavicular regions and reaches the distant sites by basically retrograde spreading in a non-random manner. The appropriate values of site involvement-rate were compared with those obtained by other authors based on pathologic staging and a good correlation was found. The high level of correspondence between these involvement-frequencies supported the general validity (i.e. valid for both treated and untreated cases) of the principles governing lymphatic spreading of HD.

Complex pathological diagnosis of granulocytic sarcoma: apropos of a case.

The diagnosis of granulocytic sarcoma can be very difficult when there is no demonstrable abnormality in the peripheral blood or bone marrow. We present the diagnostic algorithm of granulocytic sarcoma by reporting on a case mimicking large cell lymphoma without previous manifestation of acute myeloid leukemia or a myeloproliferative disorder. After standard histoprocessing, we used immunohistochemical and molecular biological methods to analyze our case. The lymph node showed diffuse infiltration of immature blast cells resembling large cell lymphoma. However, immunohistochemistry did not support this diagnosis. The tumor cells showed LCA, bcl-2, CD43, CD34 and myeloperoxidase positivity. We also detected bcl-2 gene rearrangement. In case of a lack of a specific histological picture, particularly in poorly differentiated tumors, only some minor histological signs in combination with immunohistochemistry and molecular diagnostic methods can help to render the correct diagnosis.