8 results on '"Burt, RK"'
Search Results
2. Induction of remission of severe and refractory rheumatoid arthritis by allogeneic mixed chimerism.
- Author
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Burt RK, Oyama Y, Verda L, Quigley K, Brush M, Yaung K, Statkute L, Traynor A, and Barr WG
- Subjects
- Alemtuzumab, Antibodies, Monoclonal therapeutic use, Antibodies, Monoclonal, Humanized, Antibodies, Neoplasm therapeutic use, Antigens, CD analysis, Antigens, Differentiation, Myelomonocytic analysis, Antirheumatic Agents therapeutic use, CD3 Complex analysis, Cyclophosphamide therapeutic use, Female, Humans, Immunosuppressive Agents therapeutic use, Middle Aged, Sialic Acid Binding Ig-like Lectin 3, Vidarabine therapeutic use, Arthritis, Rheumatoid therapy, Hematopoietic Stem Cell Transplantation, Transplantation Chimera, Vidarabine analogs & derivatives
- Abstract
This report describes the first allogeneic hematopoietic stem cell transplantation (HSCT) performed for the indication of rheumatoid arthritis (RA). We used nonmyeloablative allogeneic HSCT to treat a 52-year-old woman who had treatment-refractory RA and a poor prognosis (24 swollen and 38 involved joints). She was treated with fludarabine, cyclophosphamide, CAMPATH-1H, and CD34-selected HSCT (8 million CD34+ donor cells/kg); the donor was the patient's HLA-matched, rheumatoid factor-negative sister. One year post-HSCT, the patient has had no infection except dermatomal varicella-zoster virus infection and no acute or chronic graft-versus-host disease (GVHD). Her RA has remained in remission with no immunosuppressive or immunomodulatory medications. The patient is a mixed chimera, with 55% donor T (CD3+) cells and 70% donor myeloid (CD33+) cells. This is the first published report of allogeneic HSCT performed for the indication of RA. Mixed chimerism has resulted in marked amelioration of RA, without GVHD.
- Published
- 2004
- Full Text
- View/download PDF
3. Autologous hemopoietic stem cell transplantation in severe rheumatoid arthritis: a report from the EBMT and ABMTR.
- Author
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Snowden JA, Passweg J, Moore JJ, Milliken S, Cannell P, Van Laar J, Verburg R, Szer J, Taylor K, Joske D, Rule S, Bingham SJ, Emery P, Burt RK, Lowenthal RM, Durez P, McKendry RJ, Pavletic SZ, Espigado I, Jantunen E, Kashyap A, Rabusin M, Brooks P, Bredeson C, and Tyndall A
- Subjects
- Adult, Databases as Topic, Europe, Female, Humans, Male, Middle Aged, Retrospective Studies, Salvage Therapy, Transplantation, Autologous, Treatment Outcome, United States, Arthritis, Rheumatoid therapy, Hematopoietic Stem Cell Transplantation methods, Registries
- Abstract
Objective: Since 1996, autologous hemopoietic stem cell transplantation (HSCT) has been used to treat severe rheumatoid arthritis (RA). To date, published reports have been individual cases or series containing small numbers. This study combined the worldwide experience in a single analysis., Methods: The Autoimmune Disease Databases of the European Group for Blood and Marrow Transplantation (EBMT) and the Autologous Blood and Marrow Transplant Registry (ABMTR) were used to identify patients with RA treated with autologous HSCT. Further information relating to patient and treatment-specific variables was obtained by questionnaire., Results: Seventy-six patients were registered from 15 centers. Seventy-three patients had received autologous HSCT, and in 3 patients hematopoietic stem cells (HSC) were mobilized but not transplanted. Transplanted patients (median age 42 yrs, 74% female, 86% rheumatoid factor positive) had been previously treated with a mean of 5 (range 2-9) disease modifying antirheumatic drugs (DMARD). Significant functional impairment was present, with a median Health Assessment Questionnaire (HAQ) score of 1.4 (range 1.1-2.0) and Steinbrocker score mean 2.39 (SD 0.58). The high dose treatment regimen was cyclophosphamide (CYC) alone in the majority of patients, mostly 200 mg/kg (n = 62). Seven patients received anti-thymocyte globulin (ATG) in addition to CYC, 2 patients busulfan and CYC (BuCYC), and one patient CYC with total body irradiation and ATG. One patient received fludarabine with ATG. Following treatment, one patient received bone marrow but the rest received chemotherapy and/or granulocyte colony-stimulating factor mobilized peripheral blood stem cells. The harvest was unmanipulated in 28 patients, the rest receiving some form of lymphocyte depletion, mostly through CD34+ selection. Median followup was 16 months (range 3-55). Responses were measured using the American College of Rheumatology (ACR) criteria. Forty-nine patients (67%) achieved at least ACR 50% response at some point following transplant. There was a significant reduction in the level of disability measured by the HAQ (p < 0.005). Most patients restarted DMARD within 6 months for persistent or recurrent disease activity, which provided disease control in about half the cases. Response was significantly related to seronegative RA (p = 0.02) but not to duration of disease, number of previous DMARD, presence of HLA-DR4, or removal of lymphocytes from the graft. There was no direct transplant related mortality, although one patient, treated with the BuCYC regimen, died 5 months post-transplant from infection and incidental non-small cell lung cancer., Conclusion: Autologous HSCT is a relatively safe form of salvage treatment in severe, resistant RA. In these open label studies significant responses were achieved in most patients, with over 50% achieving an ACR 50 or more response at 12 months. Although the procedure is not curative, recurrent or persistent disease activity may be subsequently controlled in some patients with DMARD. Clinical trials are necessary to develop this approach in patients with aggressive disease who have failed conventional treatment including anti-tumor necrosis factor agents.
- Published
- 2004
4. Treatment of relapse after autologous blood stem cell transplantation for severe rheumatoid arthritis.
- Author
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Pavletic SZ, Klassen LW, Pope R, O'Dell JR, Traynor AE, Haire CE, Graziano F, Oyama Y, Barr W, and Burt RK
- Subjects
- Adult, Arthritis, Rheumatoid etiology, Arthritis, Rheumatoid immunology, Etanercept, Female, Follow-Up Studies, Humans, Immunoglobulin G therapeutic use, Male, Middle Aged, Receptors, Tumor Necrosis Factor therapeutic use, Recurrence, Transplantation, Autologous, Treatment Outcome, Antirheumatic Agents therapeutic use, Arthritis, Rheumatoid drug therapy, Hematopoietic Stem Cell Transplantation adverse effects, Immunosuppressive Agents therapeutic use
- Abstract
There is little information about the clinical course of patients with rheumatoid arthritis (RA) who relapse after autologous blood stem cell transplantation (ASCT). We describe 6 patients with severe RA who received ASCT in 3 US centers. Duration of followup was between 24 and 42 months posttransplant. Five patients achieved major responses but relapsed 3-22 months posttransplant. Two patients with relapse improved remarkably after restarting disease modifying antirheumatic drugs (DMARD). Two patients developed a mild RA flare at 3 and 5 months posttransplant and improved spontaneously. All 4 patients who improved after an initial disease flare remained highly functional at 14-22 months posttransplant. All patients in this study were anti-tumor necrosis factor (TNF) drug naive; all received a TNF blocker as a second line posttransplant salvage therapy, but only 3 responded. Future ASCT strategies need to focus on improving the durability of the early posttransplant responses.
- Published
- 2001
5. Future strategies in hematopoietic stem cell transplantation for rheumatoid arthritis.
- Author
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Burt RK, Barr W, Oyama Y, Traynor A, and Slavin S
- Subjects
- Clinical Trials as Topic, Forecasting, Graft vs Host Disease prevention & control, Humans, Transplantation Conditioning methods, Transplantation, Autologous, Arthritis, Rheumatoid therapy, Hematopoietic Stem Cell Transplantation trends
- Abstract
Patients with coincidental rheumatoid arthritis (RA) treated by allogeneic hematopoietic stem cell transplantation (HSCT) for drug induced aplastic anemia have been fortuitously cured of RA. Other than these examples with allogeneic HSCT, there is no known curative therapy for RA. Despite its potential to cure, allogeneic transplantation is not being offered to patients with RA due to transplant related mortality. Advances in HSCT conditioning regimens and better prevention of graft-versus-host disease should allow consideration of allogeneic HSCT as therapy for severe RA. We propose a new, well tolerated, nonmyeloablative allogeneic stem cell transplant regimen as treatment for RA.
- Published
- 2001
6. Autologous hematopoietic stem cell transplantation in refractory rheumatoid arthritis: sustained response in two of four patients.
- Author
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Burt RK, Georganas C, Schroeder J, Traynor A, Stefka J, Schuening F, Graziano F, Mineishi S, Brush M, Fishman M, Welles C, Rosen S, and Pope R
- Subjects
- Adult, Female, Follow-Up Studies, Humans, Male, Middle Aged, Outcome Assessment, Health Care, Transplantation, Autologous adverse effects, Arthritis, Rheumatoid therapy, Hematopoietic Stem Cell Transplantation adverse effects
- Abstract
Objective: To investigate the safety and efficacy of immune ablation with subsequent autologous hematopoietic stem cell transplantation (HSCT) in severe rheumatoid arthritis (RA)., Methods: Four patients with refractory RA and poor prognostic indicators were treated. Stem cells were collected and lymphocytes were depleted by 2.3-4.0 logs. The conditioning regimen included cyclophosphamide (200 mg/kg), antithymocyte globulin (90 mg/kg), and, for 1 patient, total body irradiation (TBI) with 400 cGy. Improvement was evaluated according to the American College of Rheumatology (ACR) preliminary definition of improvement in RA (ACR 20), and also according to the ACR 50 and ACR 70 criteria., Results: HSCT was well tolerated. Three patients fulfilled the ACR 70 criteria at 1 month and 3 months post-HSCT. One patient did not fulfill the ACR 20 criteria because of persistent joint tenderness, despite improvement of the joint swelling. At 6 months post-HSCT, 1 patient fulfilled the ACR 70 criteria and 1 fulfilled the ACR 50 criteria, and these 2 patients fulfilled the ACR 70 criteria at 9 months post-HSCT. The other 2 patients (including the patient who received TBI) did not meet the ACR 20 criteria at 6 months and 9 months post-HSCT. The only patient with followup of >9 months fulfilled the ACR 70 criteria at 20 months post-HSCT., Conclusion: In this series, autologous HSCT was safe and effective in inducing major clinical response and maintained significant benefit for 2 patients at 9 months and 20 months posttreatment, respectively. Sustained response did not occur for 2 of 4 patients. A regimen dose-response effect may exist, but the addition of TBI did not prevent disease relapse for 1 of the patients. More aggressive T cell depletion of the autograft, use of a myeloablative regimen, or use of an allograft may be necessary to decrease relapse rates.
- Published
- 1999
- Full Text
- View/download PDF
7. Hematopoietic stem cell transplantation of multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematosus.
- Author
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Burt RK, Traynor A, and Burns W
- Subjects
- Animals, Clinical Trials as Topic, Humans, Transplantation, Autologous, Arthritis, Rheumatoid therapy, Hematopoietic Stem Cell Transplantation adverse effects, Lupus Erythematosus, Systemic therapy, Multiple Sclerosis therapy
- Published
- 1999
- Full Text
- View/download PDF
8. Autologous Hemopoietic Stem Cell Transplantation in Severe Rheumatoid Arthritis: A Report from the EBMT and ABMTR
- Author
-
Snowden, Ja, Passweg, J., Moore, Jj, Milliken, S., Cannell, P., Laar, Jm, Verburg, R., Szer, J., Taylor, K., Joske, D., Rule, S., Bingham, Sj, Emery, P., Burt, Rk, Lowenthal, Rm, Durez, P., Mckendry, Rj, Pavletic, Sz, ILDEFONSO ESPIGADO, Jantunen, E., Kashyap, A., Rabusin, M., Brooks, P., Bredeson, C., and Tyndall, A.
- Subjects
Adult ,Male ,Salvage Therapy ,Hematopoietic Stem Cell Transplantation ,Middle Aged ,Transplantation, Autologous ,United States ,Arthritis, Rheumatoid ,Europe ,Treatment Outcome ,Databases as Topic ,Humans ,Female ,Registries ,Retrospective Studies - Abstract
Since 1996, autologous hemopoietic stem cell transplantation (HSCT) has been used to treat severe rheumatoid arthritis (RA). To date, published reports have been individual cases or series containing small numbers. This study combined the worldwide experience in a single analysis.The Autoimmune Disease Databases of the European Group for Blood and Marrow Transplantation (EBMT) and the Autologous Blood and Marrow Transplant Registry (ABMTR) were used to identify patients with RA treated with autologous HSCT. Further information relating to patient and treatment-specific variables was obtained by questionnaire.Seventy-six patients were registered from 15 centers. Seventy-three patients had received autologous HSCT, and in 3 patients hematopoietic stem cells (HSC) were mobilized but not transplanted. Transplanted patients (median age 42 yrs, 74% female, 86% rheumatoid factor positive) had been previously treated with a mean of 5 (range 2-9) disease modifying antirheumatic drugs (DMARD). Significant functional impairment was present, with a median Health Assessment Questionnaire (HAQ) score of 1.4 (range 1.1-2.0) and Steinbrocker score mean 2.39 (SD 0.58). The high dose treatment regimen was cyclophosphamide (CYC) alone in the majority of patients, mostly 200 mg/kg (n = 62). Seven patients received anti-thymocyte globulin (ATG) in addition to CYC, 2 patients busulfan and CYC (BuCYC), and one patient CYC with total body irradiation and ATG. One patient received fludarabine with ATG. Following treatment, one patient received bone marrow but the rest received chemotherapy and/or granulocyte colony-stimulating factor mobilized peripheral blood stem cells. The harvest was unmanipulated in 28 patients, the rest receiving some form of lymphocyte depletion, mostly through CD34+ selection. Median followup was 16 months (range 3-55). Responses were measured using the American College of Rheumatology (ACR) criteria. Forty-nine patients (67%) achieved at least ACR 50% response at some point following transplant. There was a significant reduction in the level of disability measured by the HAQ (p0.005). Most patients restarted DMARD within 6 months for persistent or recurrent disease activity, which provided disease control in about half the cases. Response was significantly related to seronegative RA (p = 0.02) but not to duration of disease, number of previous DMARD, presence of HLA-DR4, or removal of lymphocytes from the graft. There was no direct transplant related mortality, although one patient, treated with the BuCYC regimen, died 5 months post-transplant from infection and incidental non-small cell lung cancer.Autologous HSCT is a relatively safe form of salvage treatment in severe, resistant RA. In these open label studies significant responses were achieved in most patients, with over 50% achieving an ACR 50 or more response at 12 months. Although the procedure is not curative, recurrent or persistent disease activity may be subsequently controlled in some patients with DMARD. Clinical trials are necessary to develop this approach in patients with aggressive disease who have failed conventional treatment including anti-tumor necrosis factor agents.
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