RESUMO
Bendamustine has shown a favorable safety profile when included in chemotherapy regimens for several types of lymphoma, including CLL. This study investigated the long-term effect of adding bendamustine to a conditioning regimen on survival, rate of engraftment, immune recovery and GvHD after allogeneic stem cell transplantation (alloSCT) in CLL patients. These outcomes were compared with the fludarabine, cyclophosphamide and rituximab (FCR) conditioning regimen. We reviewed the data for 89 CLL patients treated on three trials at our institution. Twenty-six (29%) patients received bendamustine, fludarabine and rituximab (BFR) and 63 (71%) received FCR. Patient characteristics were similar in both groups. Ten (38%) BFR-treated patients vs only two (3%) FCR-treated patients did not experience severe neutropenia (P=<0.001). The 3-year overall survival estimates for the BFR and FCR groups were 82 and 51% (P=0.03), and the 3-year PFS estimates were 63% and 27% (P=0.001), respectively. The 2-year treatment-related mortality was 8 and 23% and the incidence of grade 3 or 4 GvHD was 4% and 10%, respectively. This study is the first to report that addition of bendamustine to alloSCT conditioning for CLL patients is associated with improved survival and lower mortality, myelosuppression, and GvHD.
Assuntos
Cloridrato de Bendamustina/administração & dosagem , Leucemia Linfocítica Crônica de Células B/mortalidade , Leucemia Linfocítica Crônica de Células B/terapia , Condicionamento Pré-Transplante/métodos , Adulto , Idoso , Ciclofosfamida/administração & dosagem , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Rituximab/administração & dosagem , Taxa de Sobrevida , Vidarabina/administração & dosagem , Vidarabina/análogos & derivadosRESUMO
Hematopoietic stem cell transplantation is an established treatment for many malignant and non-malignant haematological disorders. In the current case report, we describe the first haploidentical stem cell transplantation, used for the first time in Romania, the case of a 33 year-old young woman diagnosed with Hodgkin's lymphoma that has underwent a haploSCT after she relapsed from several chemotherapy regimens, as well as after an autologous stem cell transplantation. This success represents a prèmiere in Romanian clinical hematology, being the first case of a haploSCT in Romania, as well as in South-Eastern Europe.
Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Doença de Hodgkin/terapia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Haplótipos , Doença de Hodgkin/tratamento farmacológico , Humanos , Recidiva , Romênia , Condicionamento Pré-Transplante , Transplante HomólogoRESUMO
Loss of heterozygosity (LOH) has been shown to be associated with leukemia relapse after haploidentical transplantation. Whether such changes are an important cause of relapse after HLA-matched transplantation remains unclear. We retrospectively HLA-typed leukemic blasts for 71 patients with AML/myelodysplastic syndrome obtained from stored samples, and the results were compared with those obtained at diagnosis and/or before the transplant. No LOH or any other changes in HLA Ag were found in any of the samples tested post transplant as compared with pretransplant specimens. One patient had LOH in HLA class I Ag (HLA-A,-B and -C); however, these changes were present in the pretransplant sample indicating that they occurred before the transplant. We concluded that, in contrast with haploidentical transplantation, HLA loss does not have a major role as a mechanism of relapse after allogeneic transplantation with a closely HLA-matched donor.
Assuntos
Antígenos HLA/imunologia , Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia/imunologia , Leucemia/terapia , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Transplante Homólogo , Adulto JovemRESUMO
Myeloproliferative neoplasms are a category of diseases that have been traditionally amenable to allogeneic hematopoietic progenitor cell transplantation. Current developments in drug therapy have delayed transplantation for more advanced phases of the disease, especially for patients with CML, whereas transplantation remains a mainstream treatment modality for patients with advanced myelofibrosis and chronic myelomonocytic leukemia. Reduced-intensity conditioning has decreased the treatment-related mortality, and advances in the use of alternative donors for transplantation could extend the use of this procedure to an increasing number of patients with improved safety and efficacy. Here we review the current knowledge about allogeneic transplantation for myeloproliferative neoplasms and discuss the most important aspects to be considered when contemplating transplantation for patients with these diseases. Janus kinase 2 inhibitors offer the promise to improve spleen size and performance of patients with myelofibrosis and extend transplantation for patients with more advanced disease.
Assuntos
Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Mielofibrose Primária/terapia , Inibidores de Proteínas Quinases/uso terapêutico , Condicionamento Pré-Transplante/métodos , Aloenxertos , Neoplasias Hematológicas/enzimologia , Humanos , Janus Quinase 2/antagonistas & inibidores , Leucemia Mielogênica Crônica BCR-ABL Positiva/enzimologia , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/metabolismo , Mielofibrose Primária/enzimologiaAssuntos
Anemia Hemolítica/tratamento farmacológico , Anticorpos Monoclonais/uso terapêutico , Linfócitos B/imunologia , Incompatibilidade de Grupos Sanguíneos/imunologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Fatores Imunológicos/uso terapêutico , Sistema ABO de Grupos Sanguíneos/imunologia , Idoso , Anemia Hemolítica/imunologia , Anticorpos Monoclonais Murinos , Transfusão de Sangue , Feminino , Humanos , Leucemia Mielomonocítica Crônica/terapia , Rituximab , Síndrome , Transplante HomólogoAssuntos
Sobrevivência de Enxerto , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Proteínas Tirosina Quinases/antagonistas & inibidores , Condicionamento Pré-Transplante , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Haploidentical SCT (HaploSCT) has been most commonly performed using a myeloablative, TBI-based preparative regimen; however, the toxicity with this approach remains very high. We studied the feasibility of a reduced-intensity conditioning regimen in a phase II clinical trial using fludarabine, melphalan and thiotepa and antithymocyte globulin (ATG) for patients with advanced hematological malignancies undergoing T-cell depleted HaploSCT. Twenty-eight patients were entered in the study. Engraftment with donor-derived hematopoiesis was achieved in 78% of patients after a median of 13 days. Six patients experienced primary graft failure, three out of four tested patients had donor-specific anti-HLA antibodies (DSA) (P=0.001). Toxicity included mostly infections. A total of 21 out of 22 patients with AML/myelodysplastic syndrome (MDS) achieved remission after transplant (16 with relapsed/refractory AML). Five out of the 12 patients (42%) with AML/MDS with <15% BM blasts survived long term as compared with none with more advanced disease (P=0.03). HaploSCT with this fludarabine, melphalan and thiotepa and ATG RIC is an effective, well-tolerated conditioning regimen for patients with AML/MDS with low disease burden at the time of transplant and allowed a high rate of engraftment in patients without DSA. Patients with overt relapse fared poorly and require novel treatment strategies.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Agonistas Mieloablativos/administração & dosagem , Condicionamento Pré-Transplante/métodos , Adolescente , Adulto , Soro Antilinfocitário/administração & dosagem , Criança , Feminino , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Infecções/etiologia , Leucemia Mieloide Aguda/terapia , Masculino , Melfalan/administração & dosagem , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/terapia , Taxa de Sobrevida , Linfócitos T/imunologia , Tiotepa/administração & dosagem , Transplante Homólogo , Resultado do Tratamento , Vidarabina/administração & dosagem , Vidarabina/análogos & derivados , Adulto JovemAssuntos
Afasia Acinética/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Imunossupressores/efeitos adversos , Síndromes Neurotóxicas/fisiopatologia , Tacrolimo/efeitos adversos , Afasia Acinética/prevenção & controle , Monitoramento de Medicamentos , Quimioterapia Combinada/efeitos adversos , Feminino , Humanos , Imunossupressores/uso terapêutico , Leucemia Mieloide Aguda/terapia , Pessoa de Meia-Idade , Síndromes Neurotóxicas/terapia , Núcleo Familiar , Transplante de Células-Tronco/efeitos adversos , Tacrolimo/uso terapêutico , Resultado do TratamentoRESUMO
We report a case of dural venous sinus thrombosis (DVST) in a patient who developed seizures following exchange transfusion for treatment of acute chest syndrome associated with sickle cell disease. Evaluation with magnetic resonance imaging and magnetic resonance venography of the brain indicated left sigmoid sinus thrombosis. The history and laboratory evaluation did not reveal any other inherited or acquired hypercoagulable states. This is the fourth case of dural venous sinus thrombosis associated with sickle cell disease reported in literature. The patient had a favorable outcome with early treatment of unfractionated heparin.