RESUMO
BACKGROUND: To evaluate the clinical outcome of patients with relapsed or refractory follicular lymphoma treated with immunochemotherapy, in vivo purging and high-dose therapy with autotransplant. PATIENTS AND METHODS: Sixty-four patients were enrolled in the trial. Primary end point was progression-free survival (PFS). Secondary end points were the in vivo purging effect on stem-cell harvest and the impact of molecular response on the outcome. RESULTS: At enrollment, 59% of patients were PCR+ for bcl-2 rearrangement in bone marrow (PCR-informative). After the immunochemotherapy, before mobilization, 97% obtained complete response or partial response and 87% of patients informative for bcl-2 were molecularly negative. Sixty-one patients proceeded to in vivo purging and peripheral blood stem cell (PBSC) mobilization with rituximab and high-dose AraC. The median number of CD34+ cells collected was 16.6 x 10(6)/kg. Of 33 PCR-informative patients, the harvests resulted in PCR- in all. Fifty-eight patients received high-dose therapy and autotransplant of in vivo purged PBSC. After a median follow-up of 3.5 years, 41 patients are in complete remission. Five-year PFS is 59%. CONCLUSION: This study demonstrates that patients with advanced relapsed or refractory follicular lymphoma treated with immunochemotherapy, in vivo purging and autotransplant may obtain long-lasting PFS. In bcl-2-positive patients, in vivo purging allows the harvest of lymphoma-free PBSC. Absence of the bcl-2 rearrangement after autotransplant is associated with persistent clinical remission.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Purging da Medula Óssea/métodos , Linfoma Folicular/terapia , Transplante de Células-Tronco de Sangue Periférico , Adulto , Antraciclinas/administração & dosagem , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Murinos , Antígenos CD20/metabolismo , Antígenos CD34/análise , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bleomicina/administração & dosagem , Terapia Combinada , Ciclofosfamida/administração & dosagem , Citarabina/administração & dosagem , Progressão da Doença , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Esquema de Medicação , Etoposídeo/administração & dosagem , Feminino , Seguimentos , Genes bcl-2 , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Mobilização de Células-Tronco Hematopoéticas , Humanos , Fatores Imunológicos/administração & dosagem , Imunossupressores/administração & dosagem , Estimativa de Kaplan-Meier , Linfoma Folicular/tratamento farmacológico , Linfoma Folicular/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Recidiva , Indução de Remissão , Rituximab , Fatores de Tempo , Transplante Autólogo , Resultado do Tratamento , Vincristina/administração & dosagemRESUMO
From 2000 to 2004, 152 patients with multiple myeloma aged
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Mobilização de Células-Tronco Hematopoéticas/métodos , Mieloma Múltiplo/terapia , Antígenos CD34/análise , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidade , Cisplatino/administração & dosagem , Ciclofosfamida/administração & dosagem , Dexametasona/administração & dosagem , Esquema de Medicação , Etoposídeo/administração & dosagem , Estudos de Viabilidade , Humanos , Infecções/induzido quimicamente , Mieloma Múltiplo/complicações , Neutropenia/induzido quimicamente , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Transplante de Células-Tronco de Sangue Periférico/métodos , Estudos Retrospectivos , Trombocitopenia/induzido quimicamenteRESUMO
The aim of this study was to investigate thiotepa (TT) and fludarabine (Fluda) as a preparative regimen for allogeneic peripheral stem cell transplant in patients not eligible for a standard myeloablative regimen due to comorbidities and/or poor performance status. TT was given at a dose of 10 mg/kg over 2 days and Fluda at 125 mg/m(2) over 5 days. In all, 21 patients (14 male, seven female; 10 acute leukaemia, eight myelodysplastic syndrome, two non-Hodgkin's lymphoma, one Hodgkin's disease) were treated. The median age was 51 years (range 30-55 years). All patients achieved full donor-type chimaerism. Adverse events included mild nausea and vomiting in two patients and a slight increase of serum amylase in three. A total of 13 patients received RBC transfusions (median 6 U, range 1-23), and all received platelets (median 4 U, range 1-27). Four patients died of nonrelapse causes and five of relapse. The 1-year probabilities of transplant-related mortality and relapse were 19 and 29%, respectively. In total, 12 patients remain in complete remission (median follow-up: 786 days). The 3-year overall survival probability was 58%. We conclude that this regimen is feasible and well tolerated.
Assuntos
Neoplasias Hematológicas/terapia , Tiotepa/administração & dosagem , Condicionamento Pré-Transplante/métodos , Vidarabina/análogos & derivados , Vidarabina/administração & dosagem , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidade , Transfusão de Sangue , Feminino , Sobrevivência de Enxerto , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Transplante de Células-Tronco de Sangue Periférico/métodos , Recidiva , Indução de Remissão , Análise de Sobrevida , Tiotepa/toxicidade , Quimeras de Transplante , Condicionamento Pré-Transplante/efeitos adversos , Transplante Homólogo , Vidarabina/toxicidadeRESUMO
We studied a model of in vivo purging with Rituximab and high-dose (HD) cytarabine in 14 patients with relapsed/refractory follicular lymphoma and two with refractory mantle cell lymphoma enrolled in a program of HD chemotherapy and autotransplant. After two courses of debulking immunochemotherapy with Rituximab, Vincristine and Cyclophosphamide, we used a combination of Rituximab, HD cytarabine and granulocyte colony-stimulating factor for peripheral blood stem cells (PBSC) mobilization. The median number of CD34+ cells collected was 14.69 x 10(6)/kg (range 5.74-73.2). Monitoring of peripheral CD19+ and CD20+ B cells prior to and throughout the purging period showed that a treatment with Rituximab, Vincristine and Cyclophosphamide results in a profound depletion of B cells in peripheral blood. B-cell depletion persists during mobilization with Rituximab and HD cytarabine allowing a collection of PBSC free of B cells (median CD19+ and CD20+ cells counts 0%). Of nine patients PCR positive for bcl-2 or bcl-1 in blood and marrow at the start of immunochemotherapy, all showed PCR-negative PBSC. In conclusion, in patients with indolent lymphoma, the concurrent administration of Rituximab and HD cytarabine is a safe and efficient method to obtain in vivo purged PBSC. Immunochemotherapy prior to mobilization produces B-cell depletion and seems to be a useful preparative step.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Purging da Medula Óssea/métodos , Citarabina/uso terapêutico , Mobilização de Células-Tronco Hematopoéticas/métodos , Linfoma Folicular/tratamento farmacológico , Linfoma de Célula do Manto/tratamento farmacológico , Adulto , Anticorpos Monoclonais/farmacocinética , Anticorpos Monoclonais Murinos , Antígenos CD34/análise , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfócitos B/efeitos dos fármacos , Linfócitos B/imunologia , Feminino , Humanos , Imunofenotipagem , Linfoma Folicular/terapia , Linfoma de Célula do Manto/terapia , Masculino , Pessoa de Meia-Idade , Transplante de Células-Tronco de Sangue Periférico/métodos , Rituximab , Terapia de Salvação/métodos , Transplante AutólogoRESUMO
We describe a 42-year-old man with ANLL-M4 in relapse after allogeneic BMT, in whom a new CR was obtained by conventional chemotherapy followed by the infusion of his female donor PBSC. At the time of BMT he was in CR. Six months later a full hematological relapse occurred an a three drug 5-day regimen was started. Two days after the end of chemotherapy he received donor PBSC collected by two leukaphereses after mobilization with G-CSF, given subcutaneously at 5 micrograms/kg/day for 7 days. The mononuclear PBSC were 4.2 x 10(8)/kg; the CD34 positive cells were 8.2 x 10(6)/kg and the CFU-GM were 14 x 10(4)/kg. Two days after PBSC infusion the patient received G-CSF at a dose of 5 micrograms/kg/day. Hemopoietic recovery occurred promptly on day + 13 and Y-FISH revealed 14% of Y-spot positive cells in the marrow. On day +20 hematological and cytogenetic remission was documented. The percentage of recipient cells decreased from day +36 onwards following the occurrence of a grade II GVHD, from which the patient recovered 1 week later with oral cyclosporin A and intravenous high-dose steroids. At present (day +200 from relapse) the patient is still in CR with 3% of Y-spot positive cells.