Randomized controlled trials of autologous hematopoietic stem cell transplantation for autoimmune diseases: The evolution from myeloablative to lymphoablative transplant regimens

Burt, Richard K.; Marmont, A; Oyama, Yu; Slavin, Shimon; Arnold, Renate; Hiepe, Falk; Fassas, Αthanasios; Snowden, John A.; Schuening, Friedrich; Han, Mei; Patel, Dhavalkumar D.; Collier, David H.; Heslop, Helen E.; Krance, Robert; Statkute, Laisvyde; Verda, Larissa; Traynor, Ann E.; Kozák, Tomáš; Hintzen, Rogier Q.; Rose, John; Voltarelli, Júlio César; Loh, Yvonne; Territo, Mary; Cohen, Bruce A.; Craig, Robert M.; Varga, John; Barr, Walter G.

doi:10.1002/art.22256

Cited by 108 publications

(100 citation statements)

References 51 publications

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“…Mobilization is associated with flair of AID and bacteremia caused by severe cytopenias, leading to increased morbidity and mortality. 15,[63][64][65][66][67] In addition, with autologous HCT, there is a risk of relapse from reinfusion of autoreactive lymphocytes. Although many patients with malignancies have been treated by allogeneic HCT, autologous HCT has been favored over allogeneic HCT for treatment of AID because of the increased risks of morbidity and mortality from GVHD.…”

Section: Reversal Of Lupus By Transplant Of Allogeneic Hsc 1375mentioning

confidence: 99%

Reversal of autoimmune disease in lupus-prone New Zealand black/New Zealand white mice by nonmyeloablative transplantation of purified allogeneic hematopoietic stem cells

Smith-Berdan

Gille

Weissman

et al. 2007

Blood

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Patients with severe systemic lupus erythematosus (SLE) refractory to conventional treatment are candidates for autologous hematopoietic stem cell (HSC) transplantation if the intent is to reset the immunologic clock. These patients might be candidates for allotransplantation with (SLE)-resistant major histocompatibility complex (MHC) haplotype-matched HSC if partial or complete replacement of an autoimmune-prone system is the intent. Using lupus-prone New Zealand black ؋ New Zealand white (NZBW) mice, we investigated the use of highly enriched, haplomismatched, allogeneic HSC to prevent development of or to treat established autoimmune pathology. Young NZBW mice receiving purified allogeneic HSC transplants had improved survival, decreased proteinuria, circulating immune complexes, and autoantibodies to nuclear antigens than did untreated mice or mice given NZBW HSCs. NZBW mice with established lupus-like disease that received nonmyeloablative conditioning and transplants of (MHC) haplomismatched allogeneic HSCs also had greatly increased overall survival. Mice that received transplants exhibited stabilization or reversal of their lupus symptoms; stabilized or decreased proteinuria, and a lower frequency of elevated circulating immune complexes or autoantibodies than did control mice. Induction of durable mixed chimerism by transplantation of purified allogeneic HSCs after nonmyeloablative conditioning has the potential to reverse symptoms of established NZBW lupus. (Blood.

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Section: Reversal Of Lupus By Transplant Of Allogeneic Hsc 1375mentioning

confidence: 99%

Reversal of autoimmune disease in lupus-prone New Zealand black/New Zealand white mice by nonmyeloablative transplantation of purified allogeneic hematopoietic stem cells

Smith-Berdan

Gille

Weissman

et al. 2007

Blood

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“…[25][26][27][28][29][30][35][36][37][38][39][40][41][42][43][44][45] Although these studies use myeloablative conditioning regimens of varying intensity, non-myeloablative regimens have been advocated for autologous HSCT of autoimmune diseases. 46 Recently, one of these latter studies was published using CY/rATG and it reported no deaths among 21 patients with relapsing-remitting MS. 31 There is a controversy regarding the analysis of the immune system modifications as increases in naive CD4 þ T cells over memory cells 20 and the fact that more intensive regimens seem to present better results than less intensive regimens. 19,26,47 On the other hand, some studies have shown that non-myeloablative conditioning regimens containing CY þ /Àanti-T-cell antibodies induce deep changes in the immune system of patients with autoimmune diseases, with an increase in regulatory subsets of cells and of naive T cells, improvement in TCR diversity and re-establishment of the auto-tolerant state.…”

Section: Introductionmentioning

confidence: 99%

Brazilian experience with two conditioning regimens in patients with multiple sclerosis: BEAM/horse ATG and CY/rabbit ATG

Hamerschlak

Rodrigues

Moraes

et al. 2009

Bone Marrow Transplant

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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 intratransplantation period was 56% for all patients: 71.4% of the patients in the BEAM/hATG group and 40% in the CY/rATG group (P ¼ 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 a ll patients: 47% in the BEAM/hATG group and 70% in the CY/rATG group (P ¼ 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 followup would be required to fully assess the differences in therapeutic effectiveness between the two regimens.

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“…3 Currently, there is a debate as to whether patients with autoimmune disease should be treated with maximum intensity myeloablative conditioning regimens or with less intensive non-myeloablative schemes. 4 Myeloablative regimes are expected to be more effective in ablating pretransplant disease-related clones, but are complicated by treatment-related toxicities. [5][6][7][8][9] In our previous study, we found that a myeloablative conditioning regimen resulted in extensive immune renewal, yet a minority of the T-cell clones populating the peripheral blood pre-therapy was also detected in the blood post-transplantation in some patients.…”

Section: Introductionmentioning

confidence: 99%

T-cell clones persisting in the circulation after autologous hematopoietic SCT are undetectable in the peripheral CD34+ selected graft

Dubinsky

Burt

Martin

et al. 2009

Bone Marrow Transplant

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Randomized controlled trials of autologous hematopoietic stem cell transplantation for autoimmune diseases: The evolution from myeloablative to lymphoablative transplant regimens

Cited by 108 publications

References 51 publications

Reversal of autoimmune disease in lupus-prone New Zealand black/New Zealand white mice by nonmyeloablative transplantation of purified allogeneic hematopoietic stem cells

Reversal of autoimmune disease in lupus-prone New Zealand black/New Zealand white mice by nonmyeloablative transplantation of purified allogeneic hematopoietic stem cells

Brazilian experience with two conditioning regimens in patients with multiple sclerosis: BEAM/horse ATG and CY/rabbit ATG

T-cell clones persisting in the circulation after autologous hematopoietic SCT are undetectable in the peripheral CD34+ selected graft

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