RESUMO
Ibrutinib revolutionized therapy for relapsed/refractory (R/R) mantle cell lymphoma (MCL). Real-world data on the outcome of unselected patients are still limited. We analyzed 77 R/R MCL patients receiving ibrutinib with at least one prior systemic anti-lymphoma therapy. After a median follow-up of 14.0 months, 56 patients relapsed/progressed, and 45 died. The overall response rate was 66%, with 31% of complete metabolic remissions on PET/CT. The median progression-free and overall survival (OS) rates were 10.3 and 23.1 months, respectively. The median OS from ibrutinib failure was 3.7 months. High proliferation rate by Ki67 (≥ 30%) and two or more previous therapy lines both negatively correlated with outcome (HR = 2.2, p = 0.04, and HR = 2.06, p = 0.08, respectively). Female gender borderline correlated with better outcome (HR = 0.53, p = 0.08). In multivariate analysis, Ki67 and response to ibrutinib both correlated with OS (p < 0.05). Importantly, ibrutinib appeared to better control nodal and extranodal lymphoma than bone marrow (BM) involvement. From 20 patients with detectable BM infiltration (before ibrutinib initiation) achieving complete (n = 13) or partial (n = 7) metabolic remission, none achieved remission in BM. We confirmed good efficacy of ibrutinib in unselected heavily pre-treated MCL patients. Our findings support the use of a combination of ibrutinib and rituximab in patients with BM involvement.
Assuntos
Linfoma de Célula do Manto , Adulto , Humanos , Feminino , Linfoma de Célula do Manto/patologia , Antígeno Ki-67 , República Tcheca , Tomografia por Emissão de Pósitrons combinada à Tomografia ComputadorizadaRESUMO
Rituximab maintenance (RM) prolongs survival of elderly patients with mantle cell lymphoma (MCL). Persistent minimal residual disease (MRD) after induction repeatedly correlated with shorter progression-free survival (PFS). However, none of the published studies analyzed patients treated with RM. The main purpose was to analyze prognostic significance of MRD in the elderly patients with newly diagnosed MCL treated according to the recently published observational trial protocol (alternation of R-CHOP and R-cytarabine, 3 + 3 cycles, GovTrial number NCT03054883) at the centers that implemented RM. Minimal residual disease was evaluated by a EuroMRD standardized real-time PCR approach after 3 and 6 cycles of the induction therapy. Prognostic significance of MRD was analyzed in a subcohort of patients treated at the centers that implemented RM as a standard approach. Bone marrow proved to be a significantly more sensitive source for MRD detection than peripheral blood. In either compartment MRD (positive versus negative) after 3 or 6 cycles of the induction therapy did not correlate with PFS. The observed loss of prognostic significance of MRD after the R-CHOP-based induction appears to be a consequence of RM immune control over the residual lymphoma.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Linfoma de Célula do Manto , Quimioterapia de Manutenção , Rituximab/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos/administração & dosagem , Ciclofosfamida/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Feminino , Seguimentos , Humanos , Linfoma de Célula do Manto/sangue , Linfoma de Célula do Manto/tratamento farmacológico , Linfoma de Célula do Manto/mortalidade , Masculino , Pessoa de Meia-Idade , Neoplasia Residual , Prednisona/administração & dosagem , Taxa de Sobrevida , Vincristina/administração & dosagemRESUMO
Implementation of cytarabine into induction therapy became standard of care for younger patients with mantle cell lymphoma (MCL). On the basis of its beneficial impact, many centers incorporated cytarabine at lower doses also into first-line treatments of elderly patients. We conducted a multicenter observational study that prospectively analyzed safety and efficacy of alternating 3 + 3 cycles of R-CHOP and R-cytarabine for newly diagnosed transplant-ineligible MCL patients. A total of 73 patients were enrolled with median age 70 years. Most patients had intermediate (39.7%) and high-risk (50.7%) disease according to MCL international prognostic index. Rituximab maintenance was initiated in 58 patients. Overall response rate reached 89% by positron emission tomography-computed tomography, including 75.3% complete remissions. Two patients (2.7%) did not complete the induction therapy because of toxicity. Three patients (4.1%) were considered nonresponders, which led to therapy change before completion of induction. Estimated progression-free survival and overall survival were 51.3% and 68.6% at 4 years, respectively. Mantle cell lymphoma international prognostic index, bulky disease (≥ 5 cm), and achievement of positron emission tomography-negativity independently correlated with progression-free survival. Grade 3 to 4 hematologic and nonhematologic toxicity was documented in 48% and 20.5% patients, respectively. Alternation of R-CHOP and R-cytarabine represents feasible and very effective regimen for elderly/comorbid MCL patients. This study was registered at GovTrial (clinicaltrials.gov) NCT03054883.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Citarabina/uso terapêutico , Linfoma de Célula do Manto/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos/farmacologia , Anticorpos Monoclonais Murinos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Ciclofosfamida/farmacologia , Ciclofosfamida/uso terapêutico , Citarabina/farmacologia , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Feminino , Humanos , Linfoma de Célula do Manto/patologia , Masculino , Pessoa de Meia-Idade , Prednisona/farmacologia , Prednisona/uso terapêutico , Rituximab , Vincristina/farmacologia , Vincristina/uso terapêuticoAssuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma de Célula do Manto/terapia , Rituximab/uso terapêutico , Adulto , Idoso , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Linfoma de Célula do Manto/mortalidade , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Indução de Remissão/métodos , Análise de Sobrevida , Transplante AutólogoRESUMO
We analyzed 495 MCL patients from the Czech Lymphoma Study Group data registry. With the median follow-up of 4.4 years, 51.7% patients progressed or relapsed and 34.1% died. Five-year overall survival reached 65.3% and five-year progression free survival 44.1% of the patients. Maintenance rituximab (MR) after first line therapy improved overall and progression free survival compared to the patients under observation only (both p < .001). Elevated beta-2-microglobulin (p = .003), presence of systemic symptoms (p = .002), ECOG >0 (p = .003), age (p = .014), and MIPI (p < .001) were associated with MR failure. Patients who did not achieve complete remission have had two-fold higher risk of MR failure (p < .001). Autologous stem cell transplant reduced the risk of MR failure by 69% (p < .001). The MIPI and the beta-2-microglobulin were identified as independent predictors of MR failure (p = .02 and p = .03, respectively). Patients who relapsed/progressed on MR reached shorter OS calculated from the MR start compared to patients without failure (HR = 15.0; p < .001).
Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Linfoma de Célula do Manto/tratamento farmacológico , Linfoma de Célula do Manto/epidemiologia , Rituximab/efeitos dos fármacos , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica , Terapia Combinada , Ciclofosfamida , República Tcheca/epidemiologia , Doxorrubicina , Feminino , Seguimentos , Humanos , Linfoma de Célula do Manto/diagnóstico , Linfoma de Célula do Manto/mortalidade , Quimioterapia de Manutenção , Masculino , Prednisona , Prognóstico , Modelos de Riscos Proporcionais , Sistema de Registros , Rituximab/administração & dosagem , Rituximab/efeitos adversos , Análise de Sobrevida , Falha de Tratamento , Resultado do Tratamento , VincristinaRESUMO
Mantle cell lymphoma (MCL) is characterized by the hallmark t(11;14)(q13;q32) translocation, leading to cyclin D1 over-expression. Additionally, disrupting the DNA damage response pathway through ATM or TP53 defects plays an important role in MCL pathogenesis. Using deep next-generation sequencing we analyzed the mutual composition of ATM and TP53 mutations in 72 MCL patients, and assessed their impact on progression-free survival (PFS) and overall survival (OS). Mutated ATM and TP53 alleles were found in 51% (37/72) and 22% (16/72) of the cases examined, respectively, with only three patients harboring mutations in both genes. Only a mutated TP53 gene was associated with the significantly reduced PFS and OS and the same output was observed when ATM and TP53 defective groups included also sole deletions 11q and 17p, respectively. Determining the exact ATM/p53 pathway dysfunction may influence the selection of MCL patients for innovative therapies based on the targeted inhibition of selected proteins.
Assuntos
Proteínas Mutadas de Ataxia Telangiectasia/genética , Predisposição Genética para Doença , Linfoma de Célula do Manto/genética , Linfoma de Célula do Manto/patologia , Mutação , Proteína Supressora de Tumor p53/genética , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Biomarcadores Tumorais , Feminino , Estudos de Associação Genética , Humanos , Linfoma de Célula do Manto/mortalidade , Linfoma de Célula do Manto/terapia , Masculino , Prognóstico , Fatores de Transcrição SOXC/genética , Fatores de Transcrição SOXC/metabolismo , Deleção de Sequência , Proteína Supressora de Tumor p53/metabolismoRESUMO
BACKGROUND: Transplantation of mesenchymal stem cells (MSCs) is a promising therapy for degenerative spine conditions. However, cell therapy for painful spine degeneration presently requires use of contrast agents during fluoroscopy-guided injections, and the effects of these agents on MSCs represents a gap in knowledge. OBJECTIVE: To investigate the biological effects of contrast media (CM) that are coinjected with MSCs. DESIGN: Prospective observational study. SETTING: Academic medical center. PARTICIPANTS: Patient-derived clinical-grade culture expanded MSCs. INTERVENTIONS: Iohexol (Omnipaque300) was reduced to 12.5%, 25%, 50%, and 100% of the stock solution and incubated with MSCs for 30 minutes, 4 hours, and 48 hours. We also used complete media and 12.5%, 25%, 50%, 100% of phosphate-buffered saline as a control group. MAIN OUTCOME MEASURES: We examined cytotoxicity of iohexol at different concentrations and exposure duration, as well as the potential for recovery over time. Cell counts, mitochondrial activity, and quantitative real time reverse-transcriptase polymerase chain reaction of related genes were analyzed immediately after exposure (day 0) and after 2 days of exposure (day 2). RESULTS: Human MSCs exhibit a time- and concentration-dependent cytotoxic response to iodinated CM. A brief, 30-minute exposure did not affect MSCs function and viability. However, extended treatment with iohexol for 4 hours at 50% or higher concentration had a significant impact on both viability and gene expression in MSCs. CONCLUSIONS: CM (Omnipaque300) is cytotoxic to MSCs in a time-and concentration-dependent manner. Hence, the concentration of CM that accompanies MSC injections should be carefully considered during MSC therapy for disk-degenerative diseases. LEVEL OF EVIDENCE: To be determined.
RESUMO
We describe the clinical presentation of a patient with spastic diplegia, and its unique perioperative challenges. Opioids and antispasmodic medications are the primary therapy for managing pain and spasticity in the perioperative setting. However, such combination results in several side-effects and their sedative properties are synergistic. A 64-year-old woman with a history of spastic diplegia and an intrathecal baclofen pump for the treatment of her lower extremity spasticity was scheduled for a third elective left knee arthroplasty. She requested a regional anesthetic for the anticipated surgery and an opioid sparing postoperative analgesic regiment. We describe the successful use of a lumbar plexus and a sciatic nerve block as the primary anesthetic for the surgery and the use of a continuous lumbar plexus catheter for the postoperative course. Based on our patient's past anesthetic history, a regional anesthetic/analgesic technique is the ideal strategy in controlling perioperative pain and spasticity.
RESUMO
Optimal frontline treatment in younger high tumor-burden risk follicular lymphoma patients remains a challenge given the reduced efficacy of standard immunochemotherapy (R-CHOP) in widespread disease and unclear role of intensive induction. The retrospective non-randomized pair-matched (1:3) analysis compared 48 intermediate/high Follicular Lymphoma International Prognostic Index (FLIPI) patients receiving intensive rituximab sequential chemotherapy (R-SQ) with 144 random controls (R-CHOP) matched for age, FLIPI score, and maintenance delivery. Complete response rates were 91.7% and 74.1%, respectively (p = .038). After a median follow-up of 8.8 (R-SQ) and 6.5 years (R-CHOP), 5-year time to treatment failure, progression-free survival, and overall survival were 80.9%, 83.2%, and 100% and 57.5%, 60.3%, and 92.1% (p = .0044; p = .0047; p = .22), respectively. Intensive treatment was accompanied by higher acute hematologic toxicity and infections, comparable non-hematologic toxicity, and incidence of secondary malignancies. Intensive induction demonstrates superior long-term disease control compared to R-CHOP, with higher acute hematologic toxicity, but without acute treatment-related mortality. Further studies are needed to define ultra-high-risk FL patients benefiting most from treatment intensity.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Folicular/tratamento farmacológico , Linfoma Folicular/mortalidade , Adulto , Fatores Etários , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , República Tcheca/epidemiologia , Feminino , Humanos , Linfoma Folicular/diagnóstico , Linfoma Folicular/epidemiologia , Quimioterapia de Manutenção , Masculino , Análise por Pareamento , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Vigilância da População , Indução de Remissão , Resultado do Tratamento , Carga TumoralRESUMO
Mutations and deletions of the tumor suppressor TP53 gene are the most frequent genetic alterations detected in human tumors, though they are rather less frequent in lymphomas. However, acquisition of the TP53 mutation was demonstrated to be one of the characteristic markers in mantle cell lymphoma (MCL) and diffuse large B-cell lymphoma (DLBCL) and prognostic value of the TP53 status has been recognized for these diseases. We present the complex analysis of the TP53 aberrations in 57 cases of MCL and 131 cases of DLBCL. The TP53 status was determined by functional analyses in yeast (FASAY) followed by cDNA and gDNA sequencing. The level of the p53 protein was assessed by immunoblotting and loss of the TP53-specific locus 17p13.3 was detected by FISH. Altogether, we detected 13 TP53 mutations among MCL cases (22.8%) and 29 TP53 mutations in 26 from 131 DLBCL cases (19.8%). The ratio of missense TP53 mutations was 76.9% in MCL and 82.8% in DLBCL. The frequency of TP53 locus deletion was rather low in both diseases, reaching 9.3% in MCL and 15.3% in DLBCL. The presence of TP53 mutation was associated with shorter overall survival (OS) and progression-free survival (PFS) in MCL. Among DLBCL cases, the TP53 mutations shortened both OS and PFS of patients treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) and decreased both OS and PFS of patients with secondary DLBCL disease.
Assuntos
Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma de Célula do Manto/tratamento farmacológico , Prognóstico , Proteína Supressora de Tumor p53/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Ciclofosfamida/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Estimativa de Kaplan-Meier , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/patologia , Linfoma de Célula do Manto/genética , Linfoma de Célula do Manto/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Prednisona/administração & dosagem , Rituximab/administração & dosagem , Vincristina/administração & dosagem , Leveduras/genéticaRESUMO
D-type cyclins are involved in cell cycle regulation and play an important role in the pathogenesis of lymphomas. Aberrant expression of cyclin D1 is associated with mantle cell lymphoma (MCL) and serves as a diagnostic marker of MCL. Analysis of cyclin D expression in tumor tissues of patients with diffuse large B-cell lymphoma (DLBCL) which comprises a heterogeneous group of tumors may contribute to their stratification. We analyzed expression of cyclin D1, D2, and D3 mRNAs in 30 MCL and 104 DLBCL patients using qRT-PCR and addressed their significance for disease outcome. We confirmed a high level of cyclin D1 mRNA in 29 MCL cases (97%). One case (3%) was identified as positive for cyclin D2. Expression of cyclin D1 was limited to MCL and did not occur in DLBCL. Overexpression of cyclin D2, which is rare in MCL, occurred more frequently in DLBCL (11 cases, 10.6%). We showed that high expression of cyclin D2 in DLBCL cases de novo decreased the overall survival rate (P=0.016) and progression-free survival (P=0.009). The expression pattern of cyclin D3 was similar in both types of studied lymphomas and it did not affect the disease outcome.
Assuntos
Biomarcadores Tumorais/metabolismo , Ciclina D/metabolismo , Linfoma Difuso de Grandes Células B/metabolismo , Linfoma de Célula do Manto/metabolismo , Idoso , Biomarcadores Tumorais/genética , Ciclina D/genética , Feminino , Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma de Célula do Manto/mortalidade , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Minimal residual disease (MRD) detection is an essential tool for therapy response assessment in a considerable number of hematooncologic disorders, including mantle cell lymphoma (MCL). Flow cytometry (FCM) ranks among the most effective approaches, which allows rapid sample processing and compete successfully with highly sensitive molecular methods like polymerase chain reaction. Because FCM is ordinarily applied to detect MRD in B-lineage diseases like chronic lymphocytic leukemia, a similar method could be used in MCL. We decided to test our novel eight-color FCM approach in MCL MRD detection. METHODS: Using an eight-color FCM protocol designed by us, the expression of 24 selected surface antigens in a cohort of 30 patients with newly diagnosed leukemic MCL and 20 normal controls were compared to establish markers that can reliably distinguish normal B-lymphocytes from the MCL population. The sensitivity of the designed protocol was tested using serial dilution studies. RESULTS: Although MCL presents high immunophenotypic variability, the combination of CD20/23/5/19/200/62L/3/45 seems to be very favorable in flow cytometric MRD measurement. CONCLUSIONS: Our eight-color FCM protocol could easily detect MRD in MCL patients, and reaches a sensitivity of up to 2 × 10(-4) .
Assuntos
Citometria de Fluxo/métodos , Linfoma de Célula do Manto/sangue , Linfoma de Célula do Manto/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Citometria de Fluxo/normas , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasia Residual/sangue , Neoplasia Residual/diagnósticoRESUMO
Backround: Minimal residual disease (MRD) detection is an essential tool for therapy response assessment in a considerable number of hematooncologic disorders including mantle cell lymphoma (MCL). Flow cytometry (FCM) ranks among the most effective approaches which allow rapid sample processing and compete successfully with highly sensitive molecular methods like polymerase chain reaction (PCR). Since FCM is ordinarily applied to detect MRD in B-lineage diseases like chronic lymphocytic leukemia (CLL), a similar method could be used in MCL. We decided to test our novel 8-color FCM approach in MCL MRD detection. Methods: Employing an 8-color FCM protocol designed by us, the expression of 24 selected surface antigens in a cohort of 30 patients with newly diagnosed leukemic MCL and 20 normal controls were compared to one another to establish markers that can reliably distinguish normal B lymphocytes from the MCL population. The sensitivity of the designed protocol was tested using serial dilution studies. Results: Although MCL presents high immunophenotypic variability the combination of CD20/23/5/19/200/62L/3/45 appears to be very favorable in flow cytometric MRD measurement. Conclusions: Our 8-color FCM protocol could easily detect MRD in MCL patients and reaches a sensitivity of up to 2×10-4 . This article is protected by copyright. All rights reserved.
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BACKGROUND: Absolute lymphocyte count (ALC) and absolute monocyte count (AMC) have been documented as independent predictors of survival in patients with newly diagnosed Diffuse Large B-cell Lymphoma (DLBCL). Analysis of the prognostic impact of ALC and AMC in the context of International Prognostic Index (IPI) and other significant variables in elderly population treated in the R-CHOP regime has not been carried out yet. METHODOLOGY/PRINCIPAL FINDINGS: In this retrospective study, a cohort of 443 newly diagnosed DLBCL patients with age ≥ 60 was analyzed. All patients were treated with the R-CHOP therapy. An extensive statistical analysis was performed to identify risk factors of 3-year overall survival (OS). In multivariate analysis, only three predictors proved significant: Eastern Cooperative Oncology Group performance status (ECOG), age and bulky disease presence. These predictors were dichotomized (ECOG ≥ 1, age ≥ 70, bulk ≥ 7.5) to create a novel four-level score. This score predicted 3-year OS of 94.0%, 77.4%, 62.7% and 35.4% in the low-, low-intermediate, high-intermediate and high-risk groups, respectively (P<0.001). Further, a three-level score was tested which stratifies the population better (3-year OS: 91.9%, 67.2%, 36.2% in the low, intermediate and high-risk groups, respectively) but is more difficult to interpret. Both the 3- and 4-level scores were compared to standard scoring systems and, in our population, were shown to be superior in terms of patients risk stratification with respect to 3-year OS prediction. The results were successfully validated on an independent cohort of 162 patients of similar group characteristics. CONCLUSIONS: The prognostic role of baseline ALC, AMC or their ratio (LMR) was not confirmed in the multivariate context in elderly population with DLBCL treated with R-CHOP. The newly proposed age-specific index stratifies the elderly population into risk groups more precisely than the conventional IPI and its existing variants.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Linfoma Difuso de Grandes Células B/diagnóstico , Projetos de Pesquisa/estatística & dados numéricos , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos/administração & dosagem , Biomarcadores/análise , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Humanos , Contagem de Leucócitos , Linfócitos/patologia , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Monócitos/patologia , Prednisona/administração & dosagem , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Rituximab , Análise de Sobrevida , Vincristina/administração & dosagemRESUMO
The clinical course and therapy of mantle cell lymphoma (MCL) are heterogeneous and often unsatisfactory. Prognostic factors are needed to stratify the patients. Microvessel density (MVD) has prognostic significance in some malignancies. There is little information about the vasculature of MCL, although some antiangiogenic drugs are in use. We studied MVD using systematic uniform random sampling and unbiased counting frames in immunohistochemical reactions with anti-CD34 antibody in pre-therapeutic extramedullary MCL samples of 177 patients. We analyzed the relationship of MVD to overall survival (OS) and progression-free survival (PFS), as well as to proliferative activity (Ki-67), mantle cell lymphoma prognostic index (MIPI), morphological variant, pattern of growth, and localization. MVD varied widely: range 54.6-503.6 vessels/mm(2), median 158.2 vessels/mm(2). Higher MVD was associated with bone marrow infiltration at the time of diagnosis (P = 0.001). High MVD was associated with significantly worse OS (P = 0.04) only in patients treated with non-intensive (conventional) therapy. MVD correlated positively with MIPI scores but not with the proliferation, morphological variant, growth pattern, or localization. Univariate analysis identified a prognostic influence of morphological variant, MIPI, and proliferative activity on OS and PFS and a prognostic influence of bone marrow infiltration at the time of diagnosis on PFS. Multivariate analysis showed prognostic influence of MIPI and proliferative activity on OS and PFS only. In conclusion, this is the first clinicopathological study of MVD of MCL with long-term follow-up showing negative prognostic trends of high MVD in MCL and positive correlation of MVD and MIPI.
Assuntos
Linfoma de Célula do Manto/patologia , Antígenos CD34/análise , Biomarcadores Tumorais/análise , Proliferação de Células , Terapia Combinada , Intervalo Livre de Doença , Humanos , Antígeno Ki-67/análise , Linfoma de Célula do Manto/terapia , Microvasos/patologia , Microvasos/fisiologia , Prognóstico , Estudos RetrospectivosRESUMO
Although a prognostic model (MIPI, Mantle Cell Lymphoma International Prognostic Index) for patients with mantle cell lymphoma (MCL) has been established, its clinical significance for daily practice in the rituximab era remains controversial. Data of 235 unselected patients with MCL from the Czech Lymphoma Project Database were analyzed. MIPI, simplified MIPI (s-MIPI) and Ki-67 proliferation index were assessed for all patients and for a subgroup of 155 rituximab-treated (RT) patients. MIPI divided all patients into subgroups of low-risk (22%), intermediate-risk (29%) and high-risk (49%), with median overall survival 105.8 vs. 54.1 vs. 24.6 months, respectively (p < 0.001). s-MIPI revealed similar results. The validity of both indexes was confirmed in RT patients. We confirmed the Ki-67 index to be a powerful single prognostic factor for overall survival (64.4 vs. 20.1 months, p < 0.001) for all patients and for the RT subset. Our results confirm the clinical relevance of MIPI, s-MIPI and Ki-67 for risk stratification in MCL also in the rituximab era.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antígeno Ki-67/metabolismo , Linfoma de Célula do Manto/diagnóstico , Linfoma de Célula do Manto/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos/administração & dosagem , Biomarcadores/metabolismo , República Tcheca , Bases de Dados Factuais , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Imuno-Histoquímica , Linfoma de Célula do Manto/mortalidade , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Rituximab , Transplante Autólogo , Resultado do TratamentoRESUMO
Follicular lymphoma (FL) is characterized by an indolent and relapsing course. Recently, the clinical outcome of FL has been distinguished by immune microenvironment-associated gene signatures. In our study, gene expression profiling (GEP) was performed in 31 non-selected patients with follicular lymphoma (FL), 12 of whom were in relapse and the remaining 19 newly diagnosed. A custom oligonucleotide microarray (Agilent 8â×â15K) was used which contained probes for about 3500 genes, including those that had been previously published as demonstrating significant prognostic value. An unsupervised approach was not able to recognize clinically different FLs. As the previously published prognostically relevant gene signatures could not be properly verified, probably due to microarray platform differences, template matching was therefore used in order to define two gene sets with differential gene expression among our samples. These gene sets shared an overrepresentation of genes with similar biological functions and were termed 'T-CELL' and 'PROLIFERATION' profiles. The 'poor profile' was then defined by a high PROLIFERATION score (upper tertile) and/or low T-CELL score (lower tertile). The 'poor profile' cohort contained a significantly higher proportion of relapsed cases (pâ<â0.05, Fisher's exact test). Additionally, a comparison of samples from initial diagnosis and from relapse showed significant differences mainly in the T-CELL profile (pâ=â0.036; χ(2)). This supports the hypothesis that the number of T-cells and their expression pattern play a major role in FL development.