PURPOSE: In an update of the randomized, open-label, phase III European Mantle Cell Lymphoma (MCL) Elderly trial (ClinicalTrials.gov identifier: NCT00209209), published in 2012, we aimed to confirm results on long-term outcome focusing on efficacy and safety of long-term use of rituximab maintenance. PATIENTS AND METHODS: Five hundred sixty patients with newly diagnosed MCL underwent a first random assignment between rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and rituximab, fludarabine, and cyclophosphamide (R-FC) induction, followed by a second random assignment in 316 responders between rituximab and interferon alfa maintenance, to be continued until progression. We compared progression-free survival from the second randomization and overall survival (OS) from the first or second randomizations. RESULTS: After a median follow-up time of 7.6 years, the previously described difference in OS between the induction arms persisted (median, 6.4 years after R-CHOP [n = 280] v 3.9 years after R-FC [n = 280]; P = .0054). Patients responding to R-CHOP had median progression-free survival and OS times of 5.4 and 9.8 years, respectively, when randomly assigned to rituximab (n = 87), compared with 1.9 years (P < .001) and 7.1 years (P = .0026), respectively, when randomly assigned to interferon alfa (n = 97). In 58% and 32% of patients treated with R-CHOP, rituximab maintenance was still ongoing 2 and 5 years from start of maintenance, respectively. After R-FC, rituximab maintenance was associated with an unexpectedly high cumulative incidence of death in remission (22% at 5 years). Toxicity of rituximab maintenance was low after R-CHOP (grade 3-4 leukopenia or infection < 5%) but more prominent in patients on rituximab maintenance after R-FC, in whom grade 3-4 leukopenia (up to 40%) and infections were frequent (up to 15%). CONCLUSION: The excellent results of R-CHOP followed by rituximab maintenance until progression for older patients with MCL persisted in a mature follow-up. Prolongation of rituximab maintenance beyond 2 years is effective and safe.

• MeSH
• čas MeSH
• cyklofosfamid aplikace a dávkování   MeSH
• doba přežití bez progrese choroby MeSH
• doxorubicin aplikace a dávkování   MeSH
• indukční chemoterapie metody   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfom z plášťových buněk farmakoterapie   MeSH
• následné studie MeSH
• prednison aplikace a dávkování   MeSH
• protokoly antitumorózní kombinované chemoterapie terapeutické užití   MeSH
• rituximab aplikace a dávkování   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• udržovací chemoterapie metody   MeSH
• vidarabin aplikace a dávkování   analogy a deriváty   MeSH
• vinkristin aplikace a dávkování   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

• Klíčová slova
• Ibrutinib,
• MeSH
• antikoagulancia MeSH
• antitumorózní látky MeSH
• chronická lymfatická leukemie farmakoterapie   MeSH
• proteinkinasa BTK antagonisté a inhibitory   MeSH
• Publikační typ
• směrnice pro lékařskou praxi MeSH

• Konspekt
• Farmacie. Farmakologie
• NLK Obory
• farmacie a farmakologie
• farmakoterapie
• onkologie
• NLK Publikační typ
• brožury

CD52 is a glycoprotein expressed on normal as well as leukemic immune cells and shed as soluble CD52 (sCD52). We studied sCD52 levels in three CLL cohorts: the 'early', the 'high-risk', and the 'ibrutinib-treated'. The 'high-risk' patients had significantly higher sCD52 levels than the 'early' patients. For the 'early' patients, high sCD52 levels were associated with a significantly shorter time to first treatment. Regarding prognostic factors, no clear correlations with stage, IGHV, or beta-2-microglobulin were found; in a cox multivariate analysis of the 'early' patients, sCD52 and IGHV both had independent prognostic value. Following chemo-immunotherapy, sCD52 decreased in parallel with leukocytes while during ibrutinib treatment and ibrutinib-induced ymphocytosis, sCD52 decreased along with lymph node reductions. In vitro IgM stimulation of CLL cells led to increased sCD52 levels in the medium. Our findings indicate that sCD52 reflects disease activity and potentially treatment efficacy in CLL.

• MeSH
• antigen CD52 * krev   MeSH
• antitumorózní látky terapeutické užití   MeSH
• chronická lymfatická leukemie * krev   farmakoterapie   imunologie   MeSH
• lidé MeSH
• prognóza MeSH
• pyrazoly terapeutické užití   MeSH
• pyrimidiny terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

An unresolved issue in chronic lymphocytic leukemia (CLL) is whether IGHV3-21 gene usage, in general, or the expression of stereotyped B-cell receptor immunoglobulin defining subset #2 (IGHV3-21/IGLV3-21), in particular, determines outcome for IGHV3-21-utilizing cases. We reappraised this issue in 8593 CLL patients of whom 437 (5%) used the IGHV3-21 gene with 254/437 (58%) classified as subset #2. Within subset #2, immunoglobulin heavy variable (IGHV)-mutated cases predominated, whereas non-subset #2/IGHV3-21 was enriched for IGHV-unmutated cases (P = .002). Subset #2 exhibited significantly shorter time-to-first-treatment (TTFT) compared with non-subset #2/IGHV3-21 (22 vs 60 months, P = .001). No such difference was observed between non-subset #2/IGHV3-21 vs the remaining CLL with similar IGHV mutational status. In conclusion, IGHV3-21 CLL should not be axiomatically considered a homogeneous entity with adverse prognosis, given that only subset #2 emerges as uniformly aggressive, contrasting non-subset #2/IGVH3-21 patients whose prognosis depends on IGHV mutational status as the remaining CLL.

• MeSH
• analýza přežití MeSH
• antitumorózní látky terapeutické užití   MeSH
• B-lymfocyty účinky léků   imunologie   patologie   MeSH
• čas zasáhnout při rozvinutí nemoci MeSH
• chronická lymfatická leukemie diagnóza   farmakoterapie   genetika   mortalita   MeSH
• genetická heterogenita MeSH
• lidé středního věku MeSH
• lidé MeSH
• přestavba genů pro těžké řetězce B-lymfocytů imunologie   MeSH
• prognóza MeSH
• regulace genové exprese u leukemie * MeSH
• senioři MeSH
• somatická hypermutace imunoglobulinových genů MeSH
• těžké řetězce imunoglobulinů genetika   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

The randomized Haemato Oncology Foundation for Adults in The Netherlands 68 phase 3 trial compared front-line chemotherapy with chemotherapy plus the CD52 monoclonal antibody alemtuzumab for high-risk chronic lymphocytic leukemia, defined as at least 1 of the following: unmutated immunoglobulin heavy chain genes, deletion 17p or 11q, or trisomy 12. Fit patients were randomized to receive either 6 28-day cycles of oral FC chemotherapy (days 1 through 3: fludarabine 40 mg/m(2) per day and cyclophosphamide 250 mg/m(2) per day: n = 139) or FC plus subcutaneous alemtuzumab 30 mg day 1 (FCA, n = 133). FCA prolonged the primary end point, progression-free survival (3-year progression-free survival 53 vs 37%, P = .01), but not the secondary end point, overall survival (OS). However, a post hoc analysis showed that FCA increased OS in patients younger than 65 years (3-year OS 85% vs 76%, P = .035). FCA also increased the overall response rate (88 vs 78%, P = .036), and the bone marrow minimal residual disease-negative complete remission rate (64% vs 43%, P = .016). Opportunistic infections were more frequent following FCA, but without an increase in treatment related mortality (FCA: 3.8%, FC: 4.3%). FCA improves progression-free survival in high-risk chronic lymphocytic leukemia. As anticipated, FCA is more immunosuppressive than FC, but with due vigilance, does not lead to a higher treatment-related mortality. This study was registered at www.trialregister.nl as trial no. NTR529.

• MeSH
• antitumorózní látky aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• chronická lymfatická leukemie diagnóza   farmakoterapie   MeSH
• cyklofosfamid aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• humanizované monoklonální protilátky aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• přežití po terapii bez příznaků nemoci MeSH
• protokoly antitumorózní kombinované chemoterapie aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• senioři MeSH
• vidarabin aplikace a dávkování   škodlivé účinky   analogy a deriváty   terapeutické užití   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

PURPOSE: Mantle-cell lymphoma (MCL) is a distinct B-cell lymphoma associated with poor outcome. In 2008, the MCL International Prognostic Index (MIPI) was developed as the first prognostic stratification tool specifically directed to patients with MCL. External validation was planned to be performed on the cohort of the two recently completed randomized trials of the European MCL Network. PATIENTS AND METHODS: Data of 958 patients with MCL (median age, 65 years; range, 32 to 87 years) treated upfront in the trials MCL Younger or MCL Elderly were pooled to assess the prognostic value of MIPI with respect to overall survival (OS) and time to treatment failure (TTF). RESULTS: Five-year OS rates in MIPI low, intermediate, and high-risk groups were 83%, 63%, and 34%, respectively. The hazard ratios for OS of intermediate versus low and high versus intermediate risk patients were 2.1 (95% CI, 1.5 to 2.9) and 2.6 (2.0 to 3.3), respectively. MIPI was similarly prognostic for TTF. All four clinical baseline characteristics constituting the MIPI, age, performance status, lactate dehydrogenase level, and WBC count, were confirmed as independent prognostic factors for OS and TTF. The validity of MIPI was independent of trial cohort and treatment strategy. CONCLUSION: MIPI was prospectively validated in a large MCL patient cohort homogenously treated according to recognized standards. As reflected in current guidelines, MIPI represents a generally applicable prognostic tool to be used in research as well as in clinical routine, and it can help to develop risk-adapted treatment strategies to further improve clinical outcome in MCL.

• MeSH
• chemoradioterapie MeSH
• cisplatina aplikace a dávkování   MeSH
• cyklofosfamid aplikace a dávkování   MeSH
• cytarabin aplikace a dávkování   MeSH
• dexamethason aplikace a dávkování   MeSH
• dospělí MeSH
• doxorubicin aplikace a dávkování   MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfom z plášťových buněk diagnóza   patologie   terapie   MeSH
• multicentrické studie jako téma MeSH
• myší monoklonální protilátky aplikace a dávkování   MeSH
• prednison aplikace a dávkování   MeSH
• prognóza MeSH
• proporcionální rizikové modely MeSH
• protokoly antitumorózní kombinované chemoterapie aplikace a dávkování   terapeutické užití   MeSH
• randomizované kontrolované studie jako téma metody   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• staging nádorů MeSH
• transplantace periferních kmenových buněk metody   MeSH
• vinkristin aplikace a dávkování   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH