Parsaclisib is a potent and highly selective PI3Kδ inhibitor that has shown clinical benefit with monotherapy in a phase 2 study in relapsed or refractory (R/R) follicular lymphoma (FL). CITADEL-102 (NCT03039114), a phase 1, multicenter study, assessed the efficacy of parsaclisib in combination with obinutuzumab and bendamustine in patients with R/R FL. Patients were ≥18 years of age with histologically confirmed and documented CD20-positive FL, and R/R to previous rituximab-containing treatment regimens. Part one (safety run-in) determined the maximum tolerated dose of parsaclisib in combination with standard dosage regimens of obinutuzumab and bendamustine. Part two (dose expansion) was an open-label, single-group design evaluating safety, tolerability (primary endpoint), and efficacy (secondary endpoint) of parsaclisib combination therapy. Twenty-six patients were enrolled in CITADEL-102 and all patients received parsaclisib 20 mg once daily for 8 weeks, followed by 20 mg once weekly thereafter, in combination with obinutuzumab and bendamustine. One patient in safety run-in experienced a dose-limiting toxicity of grade 4 QT interval prolongation that was considered related to parsaclisib. Eight patients (30.8%) discontinued treatment due to treatment-emergent adverse events (TEAEs) of colitis (2 [7.7%]), alanine aminotransferase and aspartate aminotransferase increase (both in one patient [3.8%]), neutropenia, thrombocytopenia, QT prolongation, tonsil cancer, and maculopapular rash (each 1 [3.8%]). The most common reported TEAEs were pyrexia (53.8%), neutropenia (50.0%), and diarrhea (46.2%). Twenty-three patients (88.5%) experienced grade 3 or 4 TEAEs; the most common were neutropenia (34.6%), febrile neutropenia (23.1%), and thrombocytopenia (19.2%). Seventeen patients (65.4%) had a complete response and 3 patients (11.5%) had a partial response, for an objective response rate of 76.9%. Overall, results from CITADEL-102 suggest that the combination of parsaclisib with obinutuzumab and bendamustine did not result in unexpected safety events, with little evidence of synergistic toxicity, and demonstrated preliminary efficacy in patients with R/R FL who progressed following prior rituximab-containing regimens.

• Klíčová slova
• bendamustine hydrochloride, follicular, lymphoma, obinutuzumab, parsaclisib, phosphatidylinositol 3-kinase,
• MeSH
• bendamustin hydrochlorid MeSH
• folikulární lymfom * patologie   MeSH
• lidé MeSH
• neutropenie * chemicky indukované   MeSH
• protokoly antitumorózní kombinované chemoterapie škodlivé účinky   MeSH
• rituximab MeSH
• trombocytopenie * etiologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze I MeSH
• multicentrická studie MeSH
• Názvy látek
• bendamustin hydrochlorid MeSH
• obinutuzumab MeSH Prohlížeč
• parsaclisib MeSH Prohlížeč
• rituximab MeSH

BACKGROUND: Follicular lymphoma (FL) is the most common indolent non-Hodgkin's lymphoma in the Western world. It is an indolent disease in most patients, but about 20% of patients experience an early relapse after initial treatment, which is associated with shorter overall survival. A histological transformation into an aggressive lymphoma, most frequently diffuse large-cell B-lymphoma, represents another prognostically unfavorable event in the course of the disease. Thanks to recent genomic studies and mouse models, we are able to better understand the molecular nature of the FL onset and evolution of "aggressive" subclones of cells. Recently, deregulation of several molecular pathways associated with the histological transformation has also been described. PURPOSE: This review summarizes the complex molecular mechanisms responsible for FL onset, progression, aggressiveness, and transformation. We believe that the observations in FL have some general implications for understanding the mechanisms leading to the evolution of cancer "aggressiveness," such as divergent evolution, intraclonal variability and tumor plasticity.

• Klíčová slova
• Diffuse large B-cell lymphoma, follicular lymphoma, histological transformation, molecular mechanisms, transformed follicular lymphoma,
• MeSH
• difúzní velkobuněčný B-lymfom * genetika   patologie   MeSH
• folikulární lymfom * genetika   patologie   MeSH
• lidé MeSH
• myši MeSH
• nádorová transformace buněk genetika   metabolismus   MeSH
• nehodgkinský lymfom * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

INTRODUCTION: This double-blind, parallel-group, active-controlled phase III trial (NCT02260804) assessed CT-P10 and rituximab safety and efficacy in patients with previously untreated low-tumor-burden follicular lymphoma (LTBFL), including after a single switch from rituximab to CT-P10. PATIENTS AND METHODS: LTBFL patients were randomized (1:1) to receive CT-P10 or rituximab (375 mg/m2 intravenously; day 1 of 4 7-day cycles). Patients achieving disease control entered a 2-year maintenance period. CT-P10 or rituximab were administered every 8 weeks (6 cycles) in year 1; all patients could receive CT-P10 (every 8 weeks; 6 cycles) in year 2. Secondary endpoints (reported here) were overall response rate (ORR) during the study period, progression-free survival (PFS), time to progression (TTP), and overall survival (OS). Safety and immunogenicity were evaluated. RESULTS: Between November 9, 2015 and January 4, 2018, 258 patients were randomized (130 for CT-P10; 128 for rituximab). ORR was similar between groups over the study period (CT-P10: 88%; rituximab: 87%). After 29.2 months' median follow-up, median PFS, TTP, and OS were not estimable; 24-month Kaplan-Meier estimates suggested similarity between groups. Overall, 114 (CT-P10: 88%), and 104 (rituximab: 81%) patients experienced treatment-emergent adverse events. The single switch was well tolerated. CONCLUSION: These updated data support therapeutic similarity of CT-P10 and rituximab and support the use of CT-P10 monotherapy for previously untreated LTBFL.

• Klíčová slova
• Biosimilar, Single switch, Therapeutic similarity, Time-to-event data,
• MeSH
• biosimilární léčivé přípravky MeSH
• folikulární lymfom * farmakoterapie   patologie   MeSH
• lidé MeSH
• myší monoklonální protilátky * škodlivé účinky   MeSH
• protokoly antitumorózní kombinované chemoterapie MeSH
• rituximab škodlivé účinky   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• biosimilární léčivé přípravky MeSH
• CT-P10 MeSH Prohlížeč
• myší monoklonální protilátky * MeSH
• rituximab MeSH

PURPOSE: The PRIMA study (ClinicalTrials.gov identifier: NCT00140582) established that 2 years of rituximab maintenance after first-line immunochemotherapy significantly improved progression-free survival (PFS) in patients with follicular lymphoma compared with observation. Here, we report the final PFS and overall survival (OS) results from the PRIMA study after 9 years of follow-up and provide a final overview of safety. METHODS: Patients (> 18 years of age) with previously untreated high-tumor-burden follicular lymphoma were nonrandomly assigned to receive one of three immunochemotherapy induction regimens. Responding patients were randomly assigned (stratified by induction regimen, response to induction treatment, treatment center, and geographic region) 1:1 to receive 2 years of rituximab maintenance (375 mg/m2, once every 8 weeks), starting 8 weeks after the last induction treatment, or observation (no additional treatment). All patients in the extended follow-up provided their written informed consent (data cutoff: December 31, 2016). RESULTS: In total, 1,018 patients completed induction treatment and were randomly assigned to rituximab maintenance (n = 505) or observation (n = 513). Consent for the extended follow-up was provided by 607 patients (59.6%) of 1,018 (rituximab maintenance, n = 309; observation, n = 298). After data cutoff, median PFS was 10.5 years in the rituximab maintenance arm compared with 4.1 years in the observation arm (hazard ratio, 0.61; 95% CI, 0.52 to 0.73; P < .001). No OS difference was seen in patients randomly assigned to rituximab maintenance or observation (hazard ratio, 1.04; 95% CI, 0.77 to 1.40; P = .7948); 10-year OS estimates were approximately 80% in both study arms. No new safety signals were observed. CONCLUSION: Rituximab maintenance after induction immunochemotherapy provides a significant long-term PFS, but not OS, benefit over observation.

• MeSH
• časové faktory MeSH
• doba přežití bez progrese choroby MeSH
• dospělí MeSH
• folikulární lymfom farmakoterapie   mortalita   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• pozorné vyčkávání * MeSH
• progrese nemoci MeSH
• protinádorové látky imunologicky aktivní aplikace a dávkování   škodlivé účinky   MeSH
• rituximab aplikace a dávkování   škodlivé účinky   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH
• Názvy látek
• protinádorové látky imunologicky aktivní MeSH
• rituximab MeSH

PURPOSE: Natural killer (NK) cells are key effector cells for anti-CD20 monoclonal antibodies (mAb), such as obinutuzumab and rituximab. We assessed whether low pretreatment NK-cell count (NKCC) in peripheral blood or tumor tissue was associated with worse outcome in patients receiving antibody-based therapy. PATIENTS AND METHODS: Baseline peripheral blood NKCC was assessed by flow cytometry (CD3-CD56+ and/or CD16+ cells) in 1,064 of 1,202 patients with follicular lymphoma treated with obinutuzumab or rituximab plus chemotherapy in the phase III GALLIUM trial (NCT01332968) and 1,287 of 1,418 patients with diffuse large B-cell lymphoma (DLBCL) treated with obinutuzumab or rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (G-CHOP or R-CHOP) in the phase III GOYA trial (NCT01287741). The prognostic value of tumor NK-cell gene expression, as assessed by whole-transcriptome gene expression using TruSeq RNA sequencing, was also analyzed. The association of baseline variables, such as treatment arm, was evaluated using multivariate Cox regression models using a stepwise approach. RESULTS: In this exploratory analysis, low baseline peripheral blood NKCC was associated with shorter progression-free survival (PFS) in both follicular lymphoma [hazard ratio (HR), 1.48; 95% confidence interval (CI), 1.02-2.14; P = 0.04] and DLBCL (HR, 1.36; 95% CI, 1.01-1.83; P = 0.04), and overall survival in follicular lymphoma (HR, 2.20; 95% CI, 1.26-3.86; P = 0.0058). Low tumor NK-cell gene expression was associated with shorter PFS in G-CHOP-treated patients with DLBCL (HR, 1.95; 95% CI, 1.22-3.15; P < 0.01). CONCLUSIONS: These findings indicate that the number of NK cells in peripheral blood may affect the outcome of patients with B-cell non-Hodgkin lymphoma receiving anti-CD20-based immunochemotherapy.

• MeSH
• buňky NK imunologie   patologie   MeSH
• cyklofosfamid aplikace a dávkování   MeSH
• difúzní velkobuněčný B-lymfom krev   farmakoterapie   imunologie   patologie   MeSH
• doxorubicin aplikace a dávkování   MeSH
• folikulární lymfom krev   farmakoterapie   imunologie   patologie   MeSH
• humanizované monoklonální protilátky aplikace a dávkování   MeSH
• imunoterapie MeSH
• lidé MeSH
• míra přežití MeSH
• prednison aplikace a dávkování   MeSH
• prognóza MeSH
• protokoly antitumorózní kombinované chemoterapie terapeutické užití   MeSH
• rituximab aplikace a dávkování   MeSH
• senioři MeSH
• vinkristin aplikace a dávkování   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cyklofosfamid MeSH
• doxorubicin MeSH
• humanizované monoklonální protilátky MeSH
• obinutuzumab MeSH Prohlížeč
• prednison MeSH
• rituximab MeSH
• vinkristin MeSH

Follicular lymphoma (FL) is a common indolent B-cell malignancy with a variable clinical course. An unfavorable event in its course is histological transformation to a high-grade lymphoma, typically diffuse large B-cell lymphoma. Recent studies show that genetic aberrations of MYC or its overexpression are associated with FL transformation (tFL). However, the precise molecular mechanisms underlying tFL are unclear. Here we performed the first profiling of expression of microRNAs (miRNAs) in paired samples of FL and tFL and identified 5 miRNAs as being differentially expressed. We focused on one of these miRNAs, namely miR-150, which was uniformly downmodulated in all examined tFLs (∼3.5-fold), and observed that high levels of MYC are responsible for repressing miR-150 in tFL by binding in its upstream region. This MYC-mediated repression of miR-150 in B cells is not dependent on LIN28A/B proteins, which influence the maturation of miR-150 precursor (pri-miR-150) in myeloid cells. We also demonstrated that low miR-150 levels in tFL lead to upregulation of its target, namely FOXP1 protein, which is a known positive regulator of cell survival, as well as B-cell receptor and NF-κB signaling in malignant B cells. We revealed that low levels of miR-150 and high levels of its target, FOXP1, are associated with shorter overall survival in FL and suggest that miR-150 could serve as a good biomarker measurable in formalin-fixed paraffin-embedded tissue. Overall, our study demonstrates the role of the MYC/miR-150/FOXP1 axis in malignant B cells as a determinant of FL aggressiveness and its high-grade transformation.

• MeSH
• aktivace transkripce MeSH
• difúzní velkobuněčný B-lymfom genetika   patologie   MeSH
• down regulace MeSH
• folikulární lymfom diagnóza   genetika   patologie   MeSH
• forkhead transkripční faktory genetika   MeSH
• lidé MeSH
• mikro RNA genetika   MeSH
• nádorová transformace buněk genetika   patologie   MeSH
• prognóza MeSH
• protoonkogenní proteiny c-myc genetika   MeSH
• regulace genové exprese u nádorů * MeSH
• represorové proteiny genetika   MeSH
• upregulace MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• forkhead transkripční faktory MeSH
• FOXP1 protein, human MeSH Prohlížeč
• mikro RNA MeSH
• MIRN150 microRNA, human MeSH Prohlížeč
• protoonkogenní proteiny c-myc MeSH
• represorové proteiny MeSH

BACKGROUND: Studies in patients with rheumatoid arthritis and advanced follicular lymphoma have shown that CT-P10, a rituximab biosimilar, has equivalent or non-inferior efficacy and pharmacokinetics to rituximab. We aimed to assess the therapeutic equivalence of single-agent CT-P10 and rituximab in patients with newly diagnosed low-tumour burden follicular lymphoma. METHODS: In this ongoing, randomised, double-blind, parallel-group, active-controlled, phase 3 trial, adult patients (≥18 years) with stage II-IV low-tumour-burden follicular lymphoma were randomly assigned (1:1) using an interactive web or voice response system stratified by region, stage, and age to CT-P10 or US-sourced rituximab. Patients received CT-P10 or rituximab (375 mg/m2 intravenous) on day 1 of four 7-day cycles (induction period). Patients who had disease control after the induction period continued to a maintenance period of CT-P10 or rituximab administered every 8 weeks for six cycles and, if completed, a second year of maintenance therapy of additional CT-P10 (every 8 weeks for six cycles) was offered. The study was partially unmasked after database lock (Feb 23, 2018) for all data up to 7 months (before cycle 3 of the maintenance period). The primary endpoint was the proportion of patients who achieved an overall response by 7 months in the intention-to-treat population. Efficacy equivalence was shown if the two-sided 90% CIs for the treatment difference in the proportion of responders between CT-P10 and rituximab was within the equivalence margin of 17%. This trial is registered with ClinicalTrials.gov, number NCT02260804. FINDINGS: Between Nov 9, 2015, and Jan 4, 2018, 402 patients were assessed for eligibility, of whom 258 were randomly assigned: 130 to CT-P10 and 128 to rituximab. 108 (83%) of 130 patients assigned to CT-P10 and 104 (81%) of 128 assigned to rituximab achieved an overall response by month 7 (treatment difference estimate 1·8%; 90% CI -6·43 to 10·20). Therapeutic equivalence was shown (90% CIs were within the prespecified margin of 17%). The most common grade 3 or 4 treatment-emergent adverse events were decreased neutrophil count (two grade 3 in the CT-P10 group) and neutropenia (one in each group); all other grade 3 or 4 treatment-emergent adverse events occurred in one patient each. Six (5%) of 130 patients who received CT-P10 and three (2%) of 128 who received rituximab experienced at least one treatment-emergent serious adverse event. INTERPRETATION: CT-P10 was equivalent to rituximab in terms of efficacy and was well tolerated. CT-P10 monotherapy is suggested as a new therapeutic option for patients with low-tumour-burden follicular lymphoma. FUNDING: Celltrion, Inc.

• MeSH
• bezpečnost * MeSH
• biosimilární léčivé přípravky škodlivé účinky   farmakokinetika   farmakologie   terapeutické užití   MeSH
• dvojitá slepá metoda MeSH
• folikulární lymfom farmakoterapie   metabolismus   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• myší monoklonální protilátky škodlivé účinky   farmakokinetika   farmakologie   terapeutické užití   MeSH
• přežití po terapii bez příznaků nemoci MeSH
• rituximab škodlivé účinky   farmakokinetika   farmakologie   terapeutické užití   MeSH
• tumor burden * účinky léků   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH
• Názvy látek
• biosimilární léčivé přípravky MeSH
• CT-P10 MeSH Prohlížeč
• myší monoklonální protilátky MeSH
• rituximab MeSH

The molecular pathogenesis of follicular lymphoma (FL) was partially revealed 3 decades ago, with the discovery of the translocation that brings BCL2 under the influence of immunoglobulin heavy chain enhancers in a vast majority of cases. Despite the importance of this seminal observation, it has become increasingly clear that additional genetic alterations need to occur to trigger neoplastic transformation and disease progression. The evolution of FL involves developmental arrest and disruption of the normal function of one or more of epigenetic regulators including KMT2D/MLL2, EZH2, CBP/CREBBP, p300/EP300, and HIST1H1 in >95% of cases. B-cells "arrested" in germinal centers acquire dozens of additional genetic aberrations that influence key pathways controlling their physiological development including B Cell Receptor (BCR) signaling, PI3K/AKT, TLR, mTOR, NF-κB, JAK/STAT, MAPK, CD40/CD40L, chemokine, and interleukin signaling. Additionally, most cases of FL do not result from linear accumulation of genomic aberrations, but rather evolve from a common progenitor cell population by diverse evolution, creating multiple FL subclones in one patient. Moreover, one of the subclones might acquire a combination of aberrations involving genes controlling cell survival and proliferation including MDM2, CDKN2A/B, BCL6, MYC, TP53, β2M, FOXO1, MYD88, STAT3, or miR-17-92, and this can lead to the transformation of an initially indolent FL to an aggressive lymphoma (2%-3% risk per year). The complexity of the disease is also underscored by the importance of its interactions with the microenvironment that can substantially influence disease development and prognosis. Interpreting individual aberrations in relation to their impact on normal processes, their frequency, position in the disease evolution, and the consequences of their (co)occurrence, are the basis for understanding FL pathogenesis. This is necessary for the identification of patients with risk of early progression or transformation, for the development of novel targeted therapies, and for personalized treatment approaches. In this review, we summarize recent knowledge of molecular pathways and microenvironmental components involved in FL biology, and discuss them in the context of physiological B-cell development, FL evolution, and targeted therapies.

• Klíčová slova
• BCR signaling, Epigenetics, Follicular lymphoma, Transformation, Tumor microenvironment, miRNA,
• MeSH
• biologické markery MeSH
• epigeneze genetická MeSH
• folikulární lymfom etiologie   metabolismus   patologie   MeSH
• lidé MeSH
• nekódující RNA genetika   MeSH
• protoonkogenní proteiny c-bcl-2 genetika   metabolismus   MeSH
• receptory antigenů B-buněk metabolismus   MeSH
• regulace genové exprese u nádorů MeSH
• signální transdukce MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• biologické markery MeSH
• nekódující RNA MeSH
• protoonkogenní proteiny c-bcl-2 MeSH
• receptory antigenů B-buněk MeSH

In follicular lymphoma (FL), no prognostic index has been built based solely on a cohort of patients treated with initial immunochemotherapy. There is currently a need to define parsimonious clinical models for trial stratification and to add on biomolecular factors. Here, we confirmed the validity of both the follicular lymphoma international prognostic index (FLIPI) and the FLIPI2 in the large prospective PRIMA trial cohort of 1135 patients treated with initial R-chemotherapy ± R maintenance. Furthermore, we developed a new prognostic tool comprising only 2 simple parameters (bone marrow involvement and β2-microglobulin [β2m]) to predict progression-free survival (PFS). The final simplified score, called the PRIMA-PI (PRIMA-prognostic index), comprised 3 risk categories: high (β2m > 3 mg/L), low (β2m ≤ 3 mg/L without bone marrow involvement), and intermediate (β2m ≤ 3 mg/L with bone marrow involvement). Five-year PFS rates were 69%, 55%, and 37% in the low-, intermediate-, and high-risk groups, respectively (P < .0001). In addition, achieving event-free survival (EFS) or not at 24 months (EFS24) was a strong posttreatment prognostic parameter for subsequent overall survival, and the PRIMA-PI was correlated with EFS24. The results were confirmed in a pooled external validation cohort of 479 patients from the FL2000 LYSA trial and the University of Iowa/Mayo Clinic Lymphoma Specialized Program of Research Excellence Molecular Epidemiology Resource. Five-year EFS in the validation cohort was 77%, 57%, and 44% in the PRIMA-PI low-, intermediate-, and high-risk groups, respectively (P < .0001). The PRIMA-PI is a novel and easy-to-compute prognostic index for patients initially treated with immunochemotherapy. This could serve as a basis for building more sophisticated and integrated biomolecular scores.

• MeSH
• beta-2-mikroglobulin metabolismus   MeSH
• folikulární lymfom * metabolismus   mortalita   patologie   terapie   MeSH
• imunoterapie * MeSH
• kostní dřeň metabolismus   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• míra přežití MeSH
• nádorové proteiny metabolismus   MeSH
• přežití po terapii bez příznaků nemoci MeSH
• protokoly antitumorózní kombinované chemoterapie aplikace a dávkování   MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• beta-2-mikroglobulin MeSH
• nádorové proteiny MeSH

The aim of this study is to assess the incidence, risk factors, and outcome of biopsy-proven transformation in follicular lymphoma (FL) patients in the rituximab era. Transformation was analyzed in 1233 patients with initially diagnosed FL grades 1-3A, identified between 2002 and 2012 in the prospectively maintained Czech Lymphoma Study Group database. Only patients with histologically proven transformation (HT) were included. HT occurred in 58 cases at a median of 3.0 years from the initial FL diagnosis; the HT rate was 4% at 5 years. Transformation occurred most frequently at the first relapse (84% patients). Median OS from the HT was 2.5 years (95% CI 0.4-4.6) and 6-year OS with HT was shorter compared to all FLs (60 vs. 83.9%; 95% CI). A bulky tumor (≥ 10 cm), increased lactate dehydrogenase, age ≥ 60 years, and International Prognostic Index (intermediate/high risk), but not Follicular Lymphoma International Prognostic Index, were associated with transformation (p < 0.05). In the first line, 70% of patients received rituximab (including 36% rituximab maintenance), 57% CHOP-like regimens, and 2.6% of patients were treated with fludarabine-based therapy, whereas 11% of patients were watched only. The patients treated with R-CHOP in the first line (n = 591) showed the transformation rate at 5 years of 4.23% (95% CI 2.52-5.93); subsequent rituximab maintenance (n = 276) vs. observation (n = 153) was associated with a lower transformation rate (p.033; HR 3.29; CI 1.10-9.82). The transformation rate seems to be lower than in previous series, which may be influenced by broad use of rituximab, but prognosis of HT developed during therapy continues to be poor.

• Klíčová slova
• Follicular lymphoma, Rituximab, Transformation,
• MeSH
• analýza přežití MeSH
• antracykliny škodlivé účinky   terapeutické užití   MeSH
• biopsie MeSH
• dospělí MeSH
• folikulární lymfom farmakoterapie   epidemiologie   patologie   prevence a kontrola   MeSH
• incidence MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádorová transformace buněk účinky léků   patologie   MeSH
• následné studie MeSH
• protinádorové látky imunologicky aktivní škodlivé účinky   terapeutické užití   MeSH
• protokoly antitumorózní kombinované chemoterapie škodlivé účinky   terapeutické užití   MeSH
• registrace MeSH
• retrospektivní studie MeSH
• rituximab škodlivé účinky   terapeutické užití   MeSH
• sekundární prevence MeSH
• senioři MeSH
• udržovací chemoterapie škodlivé účinky   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH
• Názvy látek
• antracykliny MeSH
• protinádorové látky imunologicky aktivní MeSH
• rituximab MeSH