RESUMO
Despite a high proportion of patients with primary CNS lymphoma (PCNSL) experiences failure after/during first-line treatment, a few studies focused on salvage therapy are available, often with disappointing results. Herein, we report feasibility and activity of a combination of rituximab, ifosfamide and etoposide (R-IE regimen) in a multicentre series of patients with PCNSL relapsed or refractory to high-dose methotrexate-based chemotherapy. We considered consecutive HIV-negative patients ≤75 years old with failed PCNSL treated with R-IE regimen (rituximab 375 mg/m(2) , day 0; ifosfamide 2 g/m(2) /day, days1-3; etoposide 250 mg/m(2) , day 1; four courses). Twenty-two patients (median age 60 years; range 39-72; male/female ratio: 1:4) received R-IE as second-line (n = 18) or third-line (n = 4) treatment. Eleven patients had refractory PCNSL, and 11 had relapsing disease. Twelve patients had been previously irradiated. Sixty (68%) of the 88 planned courses were actually delivered; only one patient interrupted R-IE because of toxicity. Grade 4 hematological toxicity was manageable; a single case of grade 4 non-hematological toxicity (transient hepatotoxicity) was recorded. Response was complete in six patients and partial in three (overall response rate = 41%; 95%CI: 21-61%). Seven patients were successfully referred to autologous peripheral blood stem cell collection; four responders were consolidated with high-dose chemotherapy supported by autologous stem cell transplant. At a median follow-up of 24 months, eight responders did not experience relapse, two of them died of neurological impairment while in remission. Six patients are alive, with a 2-year survival after relapse of 25 ± 9%. We concluded that R-IE is a feasible and active combination for patients with relapsed/refractory PCNSL. This regimen allows stem cell collection and successful consolidation with high-dose chemotherapy and autologous transplant.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Terapia de Salvação , Idoso , Anticorpos Monoclonais Murinos/administração & dosagem , Anticorpos Monoclonais Murinos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias do Sistema Nervoso Central/radioterapia , Neoplasias do Sistema Nervoso Central/cirurgia , Terapia Combinada , Irradiação Craniana , Neoplasias dos Nervos Cranianos/tratamento farmacológico , Neoplasias dos Nervos Cranianos/radioterapia , Neoplasias dos Nervos Cranianos/cirurgia , Esquema de Medicação , Avaliação de Medicamentos , Resistencia a Medicamentos Antineoplásicos , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Neoplasias Oculares/tratamento farmacológico , Neoplasias Oculares/radioterapia , Neoplasias Oculares/cirurgia , Feminino , Seguimentos , Transplante de Células-Tronco Hematopoéticas , Humanos , Ifosfamida/administração & dosagem , Ifosfamida/efeitos adversos , Estimativa de Kaplan-Meier , Linfoma Difuso de Grandes Células B/radioterapia , Linfoma Difuso de Grandes Células B/cirurgia , Masculino , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Transplante de Células-Tronco de Sangue Periférico , Recidiva , Indução de Remissão , Estudos Retrospectivos , Rituximab , Análise de Sobrevida , Transplante Autólogo , Resultado do TratamentoRESUMO
Indolent lymphomas primarily involving the skeleton (iPBL) represent < 1% of all primary bone lymphomas. The management and prognosis have not been previously described. Patients with primary and secondary iPBL were selected from an international database of 499 patients with a histopathological diagnosis of non-Hodgkin lymphoma and skeleton involvement, and clinical features, management and prognosis were analyzed. Twenty-six (5%) patients had an iPBL. Ten patients had small lymphocytic lymphoma, 10 had follicular lymphoma and six had lymphoplasmacytic lymphoma. Eleven patients had limited stage and 15 had advanced disease. The overall response rate was 73% (95% confidence interval [CI] = 57-89%). Median follow-up was 58 months, and the 5- and 10-year progression-free survival (PFS) rates were 37 ± 10% and 25 ± 12%, respectively. Nine patients are alive, with 5- and 10-year overall survival (OS) rates of 46 ± 10% and 29 ± 11%, respectively. Patients with small lymphocytic lymphoma showed significantly better outcome than patients with follicular lymphoma. Performance status and stage of disease were independently associated with OS. The prognosis of patients with primary bone lymphoplasmacytic or follicular lymphoma was less favorable.
Assuntos
Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/terapia , Gerenciamento Clínico , Linfoma/diagnóstico , Linfoma/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/mortalidade , Feminino , Humanos , Linfoma/mortalidade , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Indução de Remissão , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Primary CNS lymphoma (PCNSL) is a rare and aggressive brain tumor with an unsatisfactory outcome. Therapeutic progress in this field is strongly conditioned by the limited biology and the molecular knowledge about this disease, which hamperizes the identification of new targeted therapies and the poor clinical conditions and performance status of patients, rendering very difficult their enrollment in prospective trials. Chemoradiation therapy is the most commonly used strategy for patients with PCNSL, which is associated with better efficacy rates, but also with high incidence of severe neurotoxicity. As a consequence, a dilemma in PCNSL treatment is the choice between strategies designed to intensify therapy to improve the cure rate, versus strategies of treatment de-escalation to avoid severe neurotoxicity. The efficacy of chemotherapy is strongly limited by the special functional and microenvironmental characteristics of the CNS, which is variably protected by the blood-brain barrier (BBB) and includes extensive chemotherapy sanctuaries where tumor cells grow undisturbed. Drugs exhibiting a good capability to cross the BBB and drugs that can be safely administered at high doses to obtain therapeutic concentrations in the CNS are the most commonly used in the treatment of PCNSL. Consolidation after chemotherapy represents the best role for radiotherapy. Since this tumor has an infiltrative nature, the whole brain should be irradiated, with increased risk of severe neurotoxicity. Some authorities are investigating in randomized trials the impact on outcome and neurotolerability of replacing consolidation radiotherapy with other strategies, like high dose chemotherapy supported by autologous stem cell transplantation. The rationale for the use of this strategy is the administration of high doses of cytostatics to achieve therapeutic concentrations in sanctuaries, CNS organs and lymphoma tissues and to overcome drug resistance mechanisms. Future therapeutic progresses in PCNSL will be based on the expansion of molecular and biological knowledge, the improvement of therapeutic efficacy and the prevention of iatrogenic neurotoxicity.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Encefálicas/terapia , Linfoma/terapia , Adulto , Fatores Etários , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Irradiação Craniana/efeitos adversos , Transplante de Células-Tronco Hematopoéticas , Humanos , Linfoma/mortalidade , Linfoma/patologia , Pessoa de Meia-Idade , Síndromes Neurotóxicas/etiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Análise de Sobrevida , Transplante AutólogoRESUMO
The aim of this study was to show a lower incidence of febrile episodes in multiple myeloma patients receiving lenograstim vs. filgrastim after high-dose cyclophosphamide for stem cell mobilization. Patients treated with cyclophosphamide were randomly assigned to receive filgrastim or lenograstim. Primary endpoint was the incidence of febrile episodes. 5.1% patients developed a febrile episode, 9.1% with filgrastim and 1.1% with lenograstim. Lenograstim group presented a significantly higher absolute CD34+ cell number compared with the filgrastim group but no differences were detected for collection efficacy. The study demonstrated a lower incidence of febrile episodes with lenograstim compared to filgrastim.