RESUMO
Based on centroblast frequency, follicular lymphoma (FL) is subdivided into grades 1-2, 3A, and 3B. Grade FL3A frequently coexists with FL1-2 (FL1-2-3A). Based on clinical trials, FL1-2 is treated with rituximab (R) or obinutuzumab plus bendamustine (B) or CHOP, while FL3B is treated with R-CHOP. In contrast, there are little data guiding therapy in FL3A. We present a retrospective, multicenter analysis of 95 FL3A or FL1-2-3A and 203 FL1-2 patients treated with R-CHOP or R-B first-line. R-CHOP facilitated a higher response rate (95% versus 76%) and longer overall survival (OS) (3-year OS 89% versus 73%, P = 0.008) in FL3A or FL1-2-3A, whereas the difference in progression-free survival (PFS) did not reach statistical significance. While transformation rates into aggressive lymphoma were similar between both groups, there were more additional malignancies after R-B compared with R-CHOP (6 versus 2 cases). In FL1-2, R-B achieved a higher 3-year PFS (79% versus 47%, P < 0.01), while there was no significant difference regarding OS or transformation. With the limitations of a retrospective analysis, these results suggest a benefit for R-CHOP over R-B in FL3A or FL1-2-3A. Confirmatory data from prospective clinical trials are needed.
Assuntos
Antineoplásicos Alquilantes/administração & dosagem , Antineoplásicos Imunológicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Cloridrato de Bendamustina/administração & dosagem , Linfoma Folicular/tratamento farmacológico , Rituximab/administração & dosagem , Idoso , Estudos de Coortes , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Seguimentos , Humanos , Linfoma Folicular/diagnóstico , Linfoma Folicular/mortalidade , Masculino , Pessoa de Meia-Idade , Gradação de Tumores/métodos , Prednisona/administração & dosagem , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Resultado do Tratamento , Vincristina/administração & dosagemRESUMO
BACKGROUND: The addition of rituximab (R) to CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) -like therapy has improved survival in primary mediastinal B-cell lymphoma (PMBCL) patients. However, these results were obtained in young low risk patients and a reevaluation in an unselected patient cohort is warranted. METHODS: In this study, we analyzed 80 PMBCL patients treated with a CHOP-based regimen with and without rituximab. RESULTS: In the non-rituximab cohort 10-year progression free survival (PFS) was 67% and 10-year overall survival (OS) was 72% versus a PFS of 95% and a OS of 92% in the rituximab group, PFS P = 0.001, OS P = 0.023. A subgroup PFS analysis by international prognostic index (IPI) risk revealed that all risk groups benefit from addition of rituximab to induction chemotherapy. In addition, OS probability was higher in the group of non-low risk patients who were treated with rituximab compared to those patients who did not receive rituximab (P = 0.035). In multivariate analysis, only addition of rituximab to induction chemotherapy and reaching complete remission (CR) after first line therapy had a beneficial effect on both PFS and OS, whereas IPI, age, upfront high dose (HD) chemotherapy/autologous blood stem cell transplantation (ABSCT) and rituximab maintenance had no impact on survival. CONCLUSIONS: Our data demonstrate a survival benefit in unselected PMBCL patients treated with CHOP-like induction regimen and additional rituximab independently of the IPI risk score.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Neoplasias do Mediastino/tratamento farmacológico , Adolescente , Adulto , Idoso , Ciclofosfamida/uso terapêutico , Intervalo Livre de Doença , Doxorrubicina/uso terapêutico , Feminino , Humanos , Estimativa de Kaplan-Meier , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Neoplasias do Mediastino/mortalidade , Pessoa de Meia-Idade , Prednisolona/uso terapêutico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Rituximab/administração & dosagem , Resultado do Tratamento , Vincristina/uso terapêutico , Adulto JovemRESUMO
BACKGROUND: Collection of peripheral blood stem cells (PBSCs) for autologous transplantation is a well-established process. As a new generation of leukapheresis (LP) machines has been launched, measures of benchmarking and quality control need to be defined in order to ensure consistent collection performance. OBJECTIVES: The goal of this project was to establish and evaluate a benchmarking system for autologous PBSC collection. METHODS: This retrospective study evaluated PBSC collection data of 198 patients with symptomatic multiple myeloma in first-line therapy who underwent LP in 2013 and 2014 at our institution. Half the patients in 2014 were assigned randomly to undergo LP with the new Terumo BCT Spectra Optia (Terumo BCT, Garching, Germany), while the COBE Spectra (Terumo BCT) was used in all other cases. In 2014, we implemented a previously described formula for predicting daily CD34+ cell collection. As a benchmark, we developed the performance ratio: collected/predicted CD34+ cells. RESULTS: There was no significant difference in the number of collected CD34+ cells, the collection efficiency (collected/processed CD34+ cells) and performance ratio between the two collection devices and between LP procedures in 2013 and 2014. CONCLUSIONS: We present a comprehensive benchmarking tool that is easy to implement, requires minimal expense and allows specific adjustment of LP parameters for optimisation of LP performance. With this approach, we could confirm the equal efficiency of the two compared apheresis systems.
Assuntos
Separação Celular , Mieloma Múltiplo/sangue , Mieloma Múltiplo/terapia , Transplante de Células-Tronco de Sangue Periférico , Células-Tronco de Sangue Periférico , Adulto , Idoso , Autoenxertos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
BACKGROUND: Rituximab (R) in combination with DHAP is a widely accepted salvage regimen for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). A common adverse effect of this protocol is renal toxicity which may result in treatment discontinuation. Assuming that a lower single dose of cisplatin over several days would reduce renal toxicity, our institution has chosen to administer cisplatin in a dosage of 25 mg/m(2) per day as a 3-h infusion over 4 consecutive days. METHODS: In this study, we analyzed the renal function of 122 patients with relapsed or refractory DLBCL treated with R-DHAP at our institution. Overall, 256 R-DHAP cycles were administered. 31 (25%), 61 (50%), 14 (12%) and 16 (13%) patients received one, two, three or four R-DHAP courses, respectively. RESULTS: A glomerular filtration rate (GFR) decrease was observed after each R-DHAP cycle. However, in none of the subgroups the median GFR was lower than 60 ml/min/1.73 m(2). In most patients, only renal impairment stage I and II was observed. Renal impairment stage III was seen in 10% and stage IV only in 1% of patients. CONCLUSION: We conclude that a modified R-DHAP regimen with administration of cisplatin 25 mg/m(2) over 4 consecutive cycles leads only to minimal renal toxicity.
Assuntos
Cisplatino/administração & dosagem , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Rituximab/administração & dosagem , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/efeitos adversos , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Humanos , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Indução de Remissão , Rituximab/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: Chemotherapy-associated ovarian damage comprises not only infertility, but also premature menopause. The latter has been reported as a consequence of alkylating chemotherapy for breast cancer or Hodgkin's lymphoma. In this study, we assessed the long-term impact of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)-like regimens on ovarian function in patients with aggressive non-Hodgkin lymphoma (NHL). PATIENTS AND METHODS: Long-term survivors after CHOP or CHOP plus etoposide (CHOEP) treatment within the Mabthera International Trial or the NHL-B1 trial of the German NHL Study Group were requested to respond to a questionnaire and to consent to blood sampling for hormone assessment. RESULTS: A total of 46 of 81 contacted patients with a median age of 32.5 years at the time of enrolment into the aforementioned clinical trials responded to the questionnaire. The median follow-up after completion of treatment was 14 years. Last menstrual bleeding occurred significantly earlier in patients compared with the general population (47 versus 51 years, P < 0.0001). In comparison to the distribution of menopausal symptoms in the general population, the percentage of women with moderate or severe menopausal symptoms was increased. In 23 patients who agreed to participate in laboratory analyses, anti-Muller hormone as a marker of ovarian reserve was decreased when compared with correspondent age groups of the general population. CONCLUSION: Although most female patients regain fertility after CHOP-like chemotherapy, late ovarian impairment occurs frequently. Therefore, awareness of such delayed side-effects at the time of counselling is of importance.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma/tratamento farmacológico , Menopausa Precoce , Insuficiência Ovariana Primária/induzido quimicamente , Sobreviventes , Adulto , Hormônio Antimülleriano/sangue , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Etoposídeo/uso terapêutico , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Testes de Função Ovariana , Prednisona/uso terapêutico , Insuficiência Ovariana Primária/sangue , Inquéritos e Questionários , Vincristina/uso terapêuticoRESUMO
For patients with diffuse large B cell lymphoma without the involvement of the CNS, the addition of rituximab to standard chemotherapy has significantly improved survival. In this single-center, retrospective analysis, a total of 81 primary CNS lymphoma (PCNSL) patients treated in our institution between 2000 and 2011 were included. Beside first-line chemotherapy with or without rituximab, we evaluated the impact of age (≤/>60 years), autologous stem cell transplantation (ASCT +/-), and other factors upon overall survival (OS) and progression-free survival (PFS). In patients treated with rituximab (n = 27), 3-year OS was 77.8 % (95 % confidence interval (CI) 62-93 %). In contrast, in patients treated without rituximab (n = 52), 3-year OS was only 39.9 % (CI 27-53 %, Fig. 1). The difference in OS was significant in the univariate (p = 0.002) as well as in the multivariate analysis (p = 0.049, hazard ratio (HR) = 0.248). Patients ≤60 years of age (n = 28) had a 3-year OS of 78.2 % (CI 63-94 %); in patients >60 years (n = 51), 3-year OS was 38.7 % (CI 25-52 %). Patients who received high-dose therapy and ASCT had a 3-year OS of 85.2 % (CI 72-99 %), and 65.1 % were alive up to the time of analysis (range 9-131 months). Without ASCT, median OS was only 16 months (CI 11-21) and 3-year OS was 35.2 % (CI 22-48 %). Age and ASCT were significantly associated with better OS in univariate (p = 0.002 and p < 0.001) as well in multivariate analysis (p = 0.004, HR = 0.023 and p = 0.001, HR = 0.014). Rituximab treatment, ASCT, and age are independent prognostic factors for OS in the first-line treatment of PCNSL.
Assuntos
Neoplasias do Sistema Nervoso Central/terapia , Transplante de Células-Tronco Hematopoéticas , Linfoma/terapia , Rituximab/administração & dosagem , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/mortalidade , Terapia Combinada , Relação Dose-Resposta a Droga , Feminino , Humanos , Linfoma/tratamento farmacológico , Linfoma/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida , Transplante AutólogoRESUMO
BACKGROUND: To improve outcome of elderly patients with diffuse large B-cell lymphoma, dose-dense rituximab was evaluated in the prospective DENSE-R-CHOP-14 trial. PATIENTS AND METHODS: Rituximab (375 mg/m(2)) was given on days 0, 1, 4, 8, 15, 22, 29, 43, 57, 71, 85, and 99 together with six CHOP-14 cycles. Results were to be compared with patients who had received the same chemotherapy in combination with eight 2-week applications of rituximab in RICOVER-60. RESULTS: One hundred twenty-four patients are assessable. Dose-dense rituximab resulted in considerably higher serum levels during the first 50 days of treatment, but rituximab exposure time was not prolonged. Grade 3 and 4 infections were exceptionally high in the first 20 patients without anti-infective prophylaxis, but decreased after introduction of prophylaxis with aciclovir and cotrimoxazole in the remaining 104 patients (from 13% to 6% per cycle and from 35% to 18% per patient; P = 0.007 and P = 0.125, respectively). Patients with international prognostic index = 3-5 had higher complete response/complete response unconfirmed rates (82% versus 68%; P = 0.033) than in the respective RICOVER-60 population, but this did not translate into better long-term outcome, even though male hazard was decreased (event-free survival: from 1.5 to 1.1; progression-free survival: from 1.7 to 1.1; overall survival: from 1.4 to 1.0). CONCLUSIONS: Dose-dense rituximab achieved higher rituximab serum levels, but was not more effective than eight 2-week applications in the historical control population, even though minor improvements in poor-prognosis and male patients cannot be excluded. The increased, though manageable toxicity, precludes its use in routine practice. Our results strongly support anti-infective prophylaxis with aciclovir and cotrimoxazole for all patients receiving R-CHOP.
Assuntos
Anticorpos Monoclonais Murinos/uso terapêutico , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Aciclovir/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Envelhecimento , Anti-Infecciosos/uso terapêutico , Anticorpos Monoclonais Murinos/efeitos adversos , Anticorpos Monoclonais Murinos/sangue , Antineoplásicos/efeitos adversos , Antivirais/uso terapêutico , Controle de Doenças Transmissíveis , Doenças Transmissíveis/tratamento farmacológico , Ciclofosfamida/uso terapêutico , Intervalo Livre de Doença , Doxorrubicina/uso terapêutico , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prednisona/uso terapêutico , Estudos Prospectivos , Rituximab , Resultado do Tratamento , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Vincristina/uso terapêuticoRESUMO
BACKGROUND: In a single-center retrospective donor versus no-donor comparison, we investigated if allogeneic stem cell transplantation (alloSCT) can improve the dismal course of poor-risk chronic lymphocytic leukemia (CLL). PATIENTS AND METHODS: All patients with CLL who were referred for evaluation of alloSCT within a 7-year time frame and had a donor search indication according to the EBMT criteria or because of Richter's transformation were included. Patients for whom a matched donor could be found within 3 months (matches) were compared with patients without such a donor (controls). Primary end point was overall survival measured from the 3-month landmark after search initiation. RESULTS: Of 105 patients with donor search, 97 (matches 83; controls 14) were assessable at the 3-month landmark. Matches and controls were comparable for age, gender, time from diagnosis, number of previous regimens, and remission status. Disregarding if alloSCT was actually carried out or not, survival from the 3-month landmark was significantly better in matches versus controls [hazard ratio 0.38, 95% confidence interval (CI) 0.17-0.85; P = 0.014]. The survival benefit of matches remained significant on multivariate analysis. CONCLUSION: This study provides first comparative evidence that alloSCT may have the potential to improve the natural course of poor-risk CLL as defined by the EBMT criteria.
Assuntos
Leucemia Linfocítica Crônica de Células B/terapia , Transplante de Células-Tronco , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Leucemia Linfocítica Crônica de Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Risco , Doadores de Tecidos , Transplante Homólogo , Resultado do TratamentoRESUMO
A 62-year-old woman presented with severe, isolated thrombocytopenia. Due to the positive family history and normal thrombocyte morphology ANKRD26-associated thrombocytopenia 2 (THC2) was suspected. The diagnosis was confirmed by DNA sequencing. Although this is the first case report on THC2 in Germany, we anticipate that THC2 might be a frequent cause of hereditary thrombocytopenia. A specific therapy was not necessary, but would consist of platelet supplementation.
Assuntos
Transtornos Cromossômicos/diagnóstico , Transtornos Cromossômicos/genética , Transtornos Hemorrágicos/diagnóstico , Transtornos Hemorrágicos/genética , Polimorfismo de Nucleotídeo Único/genética , Trombocitopenia/congênito , Quebra Cromossômica , Diagnóstico Diferencial , Feminino , Testes Genéticos , Humanos , Pessoa de Meia-Idade , Trombocitopenia/diagnóstico , Trombocitopenia/genéticaRESUMO
In most patients, mantle cell lymphoma (MCL) shows an aggressive clinical course with a continuous relapse pattern and a median survival of only 3-5 years. In the current study generation of the European MCL Network, the addition of high-dose Ara-C to R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone)-like regimen followed by myeloablative consolidation achieved a significant improvement of progression-free survival in younger patients. In elderly patients, rituximab maintenance led to a marked prolongation of remission duration. Emerging strategies include mammalian target of rapamycin (mTOR) inhibitors, proteasome inhibitors, immune modulatory drugs, Bruton's tyrosine kinase inhibitors and others, all based on the dysregulated control of cell cycle machinery and impairment of several apoptotic pathways. Combination strategies are currently being investigated in numerous trials, but their introduction into clinical practice and current treatment algorithms remains a challenge. In the current survey, the application of the molecular targeted compounds were collected and evaluated by a representative national network of 14 haematological institutions. Optimised strategies are recommended for clinical routine. Future studies will apply individualised approaches according to the molecular risk profile of the patient.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Medicina Baseada em Evidências , Linfoma de Célula do Manto/tratamento farmacológico , Adulto , Fatores Etários , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Criança , Conferências de Consenso como Assunto , Quimioterapia de Consolidação/efeitos adversos , Quimioterapia de Consolidação/métodos , União Europeia , Pesquisas sobre Atenção à Saúde , Humanos , Quimioterapia de Indução/efeitos adversos , Quimioterapia de Indução/métodos , Linfoma de Célula do Manto/prevenção & controle , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/prevenção & controle , Análise de SobrevidaRESUMO
The purpose of this study was to compare treatment and outcome of patients with Waldenström's macroglobulinemia (WM) in four private oncology practices (PP) and a university hospital (UH) in southwest Germany. We retrospectively reviewed the charts of all patients with WM of the last two decades of four PP in Mannheim, Heidelberg, Karlsruhe, and Speyer and the Department of Hematology of the University of Heidelberg. One hundred seventy patients could be identified, 74 from PP, 96 from the UH. Median age was 63.3 years. Patients from PP were older (median 65.3 vs. 62.5 years, p = 0.01). Only 54 % of patients from PP have received treatment during the observation time, as compared to 78.1 % of the UH (p < 0.001). In PP, 35 % of treated patients have received rituximab, as compared to 62.6 % of the patients of the UH (p < 0.001). Sixty percent of treated patients of PP have received bendamustine, as compared to only 8 % of the patients of the UH (p < 0.001). Time to first treatment was significantly shorter in patients from the UH compared to PP (median 13.7 vs. 52.9 months, p = 0.05). A trend towards a better overall survival was observed for patients treated with a rituximab-containing first-line regimen. The International Prognostic Scoring System for WM had significant prognostic value. Median overall survival was 25.0 years and did not differ between PP and UH. Despite different treatment strategies between PP and UH today overall survival of patients with WM is excellent, and better than previously reported.
Assuntos
Antineoplásicos/uso terapêutico , Oncologia/métodos , Macroglobulinemia de Waldenstrom/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Diagnóstico Tardio , Feminino , Alemanha , Hospitais Universitários , Humanos , Masculino , Prontuários Médicos , Pessoa de Meia-Idade , Prática Privada , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Saúde da População Urbana , Macroglobulinemia de Waldenstrom/diagnóstico , Macroglobulinemia de Waldenstrom/fisiopatologiaRESUMO
BACKGROUND: Pattern and outcome of disease recurrence after autologous stem-cell transplantation (autoSCT) for follicular lymphoma (FL) is not well known. PATIENTS AND METHODS: Relapse cases were identified from 241 consecutive patients autografted for disseminated untransformed FL from 1990 to 2002 in three institutions. Prognostic factors for relapse and outcome after relapse were analyzed by log-rank comparisons and Cox regression analyses. RESULTS: One hundred and three relapses occurred. The 10-year relapse probability was 47%. Median time from autoSCT to relapse was 20 (2-128) months. Only three relapses were observed later than 6 years posttransplant. Median survival after relapse was 8.3 years. Patients with disease recurrence within 1 year from transplant and those who had received autoSCT as second-line treatment had significantly reduced survival by multivariate analysis, whereas Follicular Lymphoma International Prognostic Index score, age, remission status at autoSCT, high-dose regimen, and ex vivo purging had no impact. CONCLUSIONS: FL recurrence after autoSCT follows a biphasic pattern with continuing relapse during the first 6 years and only few events thereafter. The prognosis after relapse is relatively good and appears to be comparable to that of disease recurrence after standard treatment. The situation is less favorable for patients who relapse within the first posttransplant year.
Assuntos
Linfoma Folicular/cirurgia , Transplante de Células-Tronco , Seguimentos , Humanos , Linfoma Folicular/patologia , Recidiva , Condicionamento Pré-Transplante , Transplante AutólogoAssuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Folicular/tratamento farmacológico , Adulto , Idoso , Anticorpos Monoclonais Murinos/administração & dosagem , Anticorpos Monoclonais Murinos/efeitos adversos , Anticorpos Monoclonais Murinos/economia , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/economia , Biomarcadores Tumorais , Análise Custo-Benefício , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Ciclofosfamida/economia , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Doxorrubicina/economia , Humanos , Estimativa de Kaplan-Meier , Linfoma Folicular/economia , Linfoma Folicular/genética , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Prednisona/economia , Modelos de Riscos Proporcionais , Indução de Remissão , Rituximab , Resultado do Tratamento , Vincristina/administração & dosagem , Vincristina/efeitos adversos , Vincristina/economia , Adulto JovemRESUMO
Several biological and clinical considerations suggest the involvement of cyclooxygenase-2 (COX-2), the key enzyme of prostaglandin (PG) synthesis, in the pathogenesis and progression of haematological malignancies. Despite the wealth of data concerning COX-2 expression, only limited information is available on multiple myeloma (MM). Using standard immunohistochemistry we therefore evaluated COX-2 protein expression in samples from 57 patients with a primary diagnosis of MM. Time to progression and a variety of clinicopathological features were evaluated by the Kaplan-Meier method and the Cox regression model. In addition, COX-2 expression was evaluated by staining bone marrow from healthy donors and 11 patients with MGUS. Overall, 31 MM samples (54%) expressed COX-2. Positivity for COX-2 was unrelated to stage or clinical or molecular features of the disease. However, patients with COX-2 positive tumours experienced a significantly shorter time to progression (17 vs 30 months, p = 0.037). In summary, COX-2 is frequently expressed in MM and correlates with shorter progression-free survival.
Assuntos
Ciclo-Oxigenase 2/metabolismo , Mieloma Múltiplo/enzimologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Humanos , Imuno-Histoquímica/métodos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/metabolismo , Mieloma Múltiplo/patologia , Modelos de Riscos Proporcionais , Análise de SobrevidaRESUMO
In this phase I/II study, we explored the combination of Temsirolimus with Bendamustine and Rituximab (BeRT) in patients with r/r follicular lymphoma (FL) or mantle cell lymphoma (MCL). Patients with 1-3 prior therapies received Bendamustine (90 mg/m(2), day 1+2) and Rituximab (375 mg/m(2), day 1) with Temsirolimus in doses from 25 to 75 mg added on day 1, 8, 15 of a 28-day cycle. Fifteen (11 MCL, 4 FL) patients were included in the phase I. Median age was 73 years and median pretreatment number was 2. No formal dose-limiting toxicity was observed. Dominant non-hematological side effects were fatigue in 11 (73%), nausea in 9 (60%), mucositis in 7 (47%) and vomiting in 6 patients (40%). Cough, diarrhea, pyrexia and rash were observed in five patients (33%) each. Grade 3/4 events included leukopenia in 6 (40%), neutropenia in 4 (27%) and thrombocytopenia in 2 patients (13%). An objective response was observed in 14/15 patients (93%), including 5 complete response (33%; all MCL). After a median follow-up of 19 months, 67% of patients are without signs of progression. Temsirolimus can be safely added to BR with promising preliminary activity. Recruitment in phase II is ongoing.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Folicular/tratamento farmacológico , Linfoma de Célula do Manto/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Idoso , Anticorpos Monoclonais Murinos/administração & dosagem , Cloridrato de Bendamustina , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Linfoma Folicular/mortalidade , Linfoma Folicular/patologia , Linfoma de Célula do Manto/mortalidade , Linfoma de Célula do Manto/patologia , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Compostos de Mostarda Nitrogenada/administração & dosagem , Prognóstico , Estudos Prospectivos , Indução de Remissão , Rituximab , Segurança , Sirolimo/administração & dosagem , Sirolimo/análogos & derivados , Taxa de SobrevidaRESUMO
To elucidate factors contributing to the effectiveness of allogeneic hematopoietic stem cell transplantation (alloHCT) in high-risk CLL, immune interventions, GvHD and clinical outcome of 77 consecutive patients allografted for CLL were analyzed. Immune modulation (immunosuppression tapering, rituximab-augmented donor lymphocyte infusions) was guided by minimal residual disease (MRD) monitoring and commenced at a median of 91 (22-273) days after alloHCT, resulting in a probability of being event free and MRD-negative 1 year after transplant of 57% (84% in those encountering chronic GvHD). Patients who were event free and MRD-negative at the 12-month landmark had a 4-year PFS of 77% and largely remained durably MRD-negative if MRD clearance had occurred subsequent to immune modulation. Three-year overall survival, PFS, relapse incidence and non-relapse mortality of all 77 patients were 69, 57, 26 and 24%, respectively. Survival was not affected by EBMT risk category but by active disease at alloHCT, which could not be overcome by intensification of conditioning. Twenty-three patients who experienced relapse post alloHCT had a survival of 56% at 2 years after CLL recurrence. In conclusion, MRD-guided immune modulation after alloHCT for high-risk CLL can provide durable MRD clearance in more than half of the patients.