Subject(s)
Cord Blood Stem Cell Transplantation/methods , Fetal Stem Cells/transplantation , Hematologic Diseases/surgery , Transplantation, Haploidentical/methods , Adolescent , Adult , Aged , Child , Child, Preschool , Cross-Sectional Studies , Disease-Free Survival , Female , Graft vs Host Disease/epidemiology , Hematologic Diseases/mortality , Hematopoietic Stem Cell Transplantation , Humans , Infant , Infant, Newborn , Kaplan-Meier Estimate , Latin America , Length of Stay , Male , Middle Aged , Postoperative Complications/epidemiology , Pregnancy , Young AdultABSTRACT
Patients with refractory severe aplastic anemia (SAA) who lack a matched sibling or unrelated donor need new therapeutic approaches. Hematopoietic SCT (HSCT) using mismatched or haploidentical related donors has been used in the past, but was associated with a significant risk of GVHD and mortality. Recently, the use of post-transplant cyclophosphamide (Cy) has been shown to be an effective strategy to prevent GVHD in recipients of haploidentical HSCT, but the majority of reports have focused on patients with hematology malignancies. We describe the outcome of 16 patients who underwent haploidentical transplantation using a reduced-intensity conditioning regimen with post-transplant Cy. Stem cell sources were BM (N=13) or PBSCs (N=3). The rate of neutrophil engraftment was 94% and of platelet engraftment was 75%. Two patients had secondary graft failure and were successfully salvaged with another transplant. Three patients developed acute GVHD being grades 2-4 in two. Five patients have died and the 1-year OS was 67.1% (95% confidence interval: 36.5-86.4%). In our small series, the use of a reduced-intensity conditioning with post-transplant Cy in haploidentical BMT was associated with high rates of engraftment and low risk of GVHD in patients with relapsed/refractory SAA.
Subject(s)
Anemia, Aplastic/therapy , Bone Marrow Transplantation , Cyclophosphamide/administration & dosage , Graft vs Host Disease/prevention & control , Immunosuppressive Agents/administration & dosage , Transplantation Conditioning , Acute Disease , Adolescent , Adult , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Retrospective StudiesABSTRACT
Studies have shown that autologous hematopoietic SCT (HSCT) can be used as an intensive immunosuppressive therapy to treat refractory patients and to prevent the progression of multiple sclerosis (MS). This is a prospective multicentric Brazilian MS trial comparing two conditioning regimens: BEAM/horse ATG and CY/rabbit ATG. Most (80.4%) of the 41 subjects in the study had the secondary progressive MS subtype and the mean age was 42 years. The baseline EDSS score in 58.5% of the subjects was 6.5 and 78% had a score of 6.0 or higher, respectively. The complication rate during the intra-transplantation period was 56% for all patients: 71.4% of the patients in the BEAM/hATG group and 40% in the CY/rATG group (P=0.04). Three subjects (7.5%) died of cardiac toxicity, sepsis and alveolar hemorrhage, all of them in the BEAM/ATG group. EFS was 58.54% for all patients: 47% in the BEAM/hATG group and 70% in the CY/rATG group (P=0.288). In conclusion, the CY/rATG regimen seems to be associated with similar outcome results, but presented less toxicity when compared with the BEAM/hATG regimen. Long-term follow-up would be required to fully assess the differences in therapeutic effectiveness between the two regimens.
Subject(s)
Hematopoietic Stem Cell Transplantation/methods , Multiple Sclerosis/therapy , Transplantation Conditioning/methods , Adult , Animals , Antilymphocyte Serum/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Carmustine/administration & dosage , Cytarabine/administration & dosage , Etoposide/administration & dosage , Female , Graft Rejection/prevention & control , Hematopoietic Stem Cell Mobilization , Horses , Humans , Male , Melphalan/administration & dosage , Middle Aged , Quality of Life , RabbitsABSTRACT
OBJECTIVE: Rituximab, a monoclonal antibody against B-lymphocytes that express CD 20, is already available for the treatment of non-Hodgkin's lymphoma. Due to the increased relevance of B-cell regulation in the pathogenesis of autoimmune diseases, rituximab is being used in the treatment of patients whose condition is refractory to conventional therapy. METHODS: We retrospectively evaluated the short-term efficacy and tolerance of rituximab in patients with various autoimmune diseases who were treated at the Hospital Israelita Albert Einstein in the city of Sao Paulo. RESULTS: During the period 2002-2004, 29 patients with various autoimmune diseases were treated with rituximab 375 mg/m2 for 4 consecutive weeks, or two doses of 1 g 2 weeks apart. We observed remarkable short-term results in all cases, except for one patient with thrombocytopenic purpura. Of note, we describe the results in two patients with diseases not previously treated with rituximab (hypergammaglobulinemic purpura of Waldenstrom and eosinophilic fasciitis with hypergammaglobulinemia). Treatment was well tolerated, with no unexpected adverse events. We also observed a marked reduction in steroid dosage. CONCLUSION: Rituximab seems to be safe and effective in the treatment of patients with a variety of autoimmune diseases that are refractory to other modalities of treatment.
Subject(s)
Antibodies, Monoclonal/therapeutic use , Autoimmune Diseases/drug therapy , Immunologic Factors/therapeutic use , Adolescent , Adult , Aged , Anemia, Hemolytic, Autoimmune/diagnosis , Anemia, Hemolytic, Autoimmune/drug therapy , Anemia, Hemolytic, Autoimmune/physiopathology , Antibodies, Monoclonal, Murine-Derived , Arthritis, Rheumatoid/diagnosis , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/physiopathology , Autoimmune Diseases/diagnosis , Autoimmune Diseases/physiopathology , Brazil , Child , Drug Therapy, Combination , Female , Humans , Lupus Erythematosus, Systemic/diagnosis , Lupus Erythematosus, Systemic/drug therapy , Lupus Erythematosus, Systemic/physiopathology , Male , Middle Aged , Purpura, Thrombocytopenic, Idiopathic/diagnosis , Purpura, Thrombocytopenic, Idiopathic/drug therapy , Purpura, Thrombocytopenic, Idiopathic/physiopathology , Retrospective Studies , Rituximab , Treatment OutcomeABSTRACT
A deficiência de antitrombina III (ATIII) é observada na hepatopatia grave e pode ser decorrente da reduçäo de síntese ou de consumo aumentado, o que poderia ser compensado com o uso de concentrado de ATIII. OBJETIVO. Avaliar a eficiência da administraçäo de uma dose fixa de concentrado de ATIII, em pacientes com hepatopatia descompensada com distúrbio de hemostasia. CASUISTICA E MÉTODO. Foram avaliados seis pacientes, com idade média de 44 anos, variando de 14 a 63 anos, portadores de cirrose (quatro de etiologia alcoólica, um viral e um doença de Wilson), com alteraçäo de pelo menos dois dos parâmetros da hemostasia (TP> 1,40, TTPA> 1,25, fibrinogênio < 1,5g/L, plaquetas < 80.000/mm3). A média do nível de albumina foi de 2,6g/dL (1,9 a 3,8g/dL). O concentrado de ATIII (Kybernin) foi administrado na dose de 50U/kg, em dias alternados. Foi colhido sangue antes da primeira infusäo, 4 horas após e, depois, diariamente, antes da infusäo do dia, para medida da ATIII plasmática (amidolítico). Nenhum paciente recebeu hemoderivados. RESULTADOS. As médias da dosagem de ATIII foram: inicial = 35,8 por cento, 4 horas = 56,2 por cento*, 2 dias = 48,7 por cento*, 4 dias = 45,7 por cento* e 8 dias = 42,3 por cento*. Após a infusäo houve elevaçäo significante dos níveis de ATIII (* = p < 0,02, teste de Friedman), que se manteve até o 4§ dia. Näo houve alteraçäo dos demais parâmetros de coagulaçäo. CONCLUSÕES. O uso de concentrado de ATIII na dose utilizada é suficiente para elevar os níveis desse inibidor na hepatopatia; entretanto, com essa dose näo se obteve normalizaçäo de seus níveis. Esses dados sugerem que doses mais elevadas devem ser usadas em pacientes com hepatopatias graves, que apresentam näo apenas reduçäo de síntese, mas aumento de consumo dos fatores da coagulaçäo e de seus inibidores.
