The rationale behind autologous autoimmune hematopoietic stem cell transplant conditioning regimens: concerns over the use of total-body irradiation in systemic sclerosis

Burt, Richard K.; Kallunian, K; Patel, Dhavalkumar D.; Thomas, James W.; Yeager, Andrew M.; Traynor, Ann E.; Heipe, F.; Arnold, Renate; Marmont, A; Collier, David H.; Glatstein, Eli; Snowden, John A.

doi:10.1038/sj.bmt.1704671

Cited by 26 publications

(29 citation statements)

References 57 publications

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“…The major difference between the FHRCC myeloablative and our current non-myeloablative transplant regimens used for SSc is the use of TBI. 10 Owing to the concerns over the use of TBI in the conditioning regimen, 10,12 as well as the rationale for transplant, that is myeloablation vs lymphoablation, we used a non-myeloablative regimen based on dose escalation of CY, an agent with previously reported efficacy for SSc. Since this regimen is non-myeloablative, hematopoietic reconstitution may occur without hematopoietic stem cell re-infusion.…”

Section: Discussionmentioning

confidence: 99%

“…11 After HSCT using a TBI-based myeloablative conditioning regimen, the efficacy data in terms of modified Rodnan skin score (mRSS) appear promising; 6,8,9 however, substantial treatment-related toxicity including mortality and treatment-related deterioration of internal organ (lung and kidney) function and radiation-related myelodysplastic syndrome/leukemia has tempered enthusiasm for this approach. 9,10,12 In contrast, non-myeloablative non-radiation containing autologous HSCT regimens have been utilized to treat safely both systemic lupus erythematosus 13 and type I diabetes mellitus.…”

Section: Introductionmentioning

confidence: 99%

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Autologous non-myeloablative hematopoietic stem cell transplantation in patients with systemic sclerosis

Oyama

Barr

Statkute

et al. 2007

Bone Marrow Transplant

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Autologous hematopoietic stem cell transplantation (HSCT) utilizing a myeloablative regimen containing total body irradiation has been performed in patients with systemic sclerosis (SSc), but with substantial toxicity. We, therefore, conducted a phase I non-myeloablative autologous HSCT study in 10 patients with SSc and poor prognostic features. PBSC were mobilized with CY and G-CSF. The PBSC graft was cryopreserved without manipulation and re-infused after the patient was treated with a non-myeloablative conditioning regimen of 200 mg/kg CY and 7.5 mg/kg rabbit antithymocyte globulin. There was a statistically significant improvement of modified Rodnan skin score whereas cardiac (ejection fraction, pulmonary arterial pressure), pulmonary function (DLCO) and renal function (creatinine) remained stable without significant change. One patient with advanced disease died 2 years after the transplant from progressive disease. After median follow-up of 25.5 months, the overall and progression-free survival rates are 90 and 70% respectively. Autologous HSCT utilizing a non-myeloablative conditioning regimen appears to result in improved skin flexibility similar to a myeloablative TBI containing regimen, but without the toxicity and risks associated with TBI.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Autologous non-myeloablative hematopoietic stem cell transplantation in patients with systemic sclerosis

Oyama

Barr

Statkute

et al. 2007

Bone Marrow Transplant

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“…scleroderma) has been associated with excessive toxicity, precluding further use of this method in this setting. 78 The mean dose of radiation to the lung might have an independent predictive value with regard to pulmonary-toxicity-related mortality in the setting of both autologous and allogeneic stem-cell transplantation. 76 Lung shielding appears to be relatively effective at reducing incidence of pulmonary toxicities, but its value is still in question.…”

Section: Rationale For Immunodepletionmentioning

confidence: 99%

Increased intensity lymphodepletion and adoptive immunotherapy—how far can we go?

et al. 2006

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SummaryIn a recent clinical trial involving patients with metastatic melanoma, immunosuppressive conditioning with fludarabine and cyclophosphamide resulted in a 50% response rate and a robust long-term persistence of adoptively transferred T cells. Experimental findings indicate that lymphodepletion prior to adoptive transfer of tumor-specific T lymphocytes plays a key role in enhancing treatment efficacy by eliminating regulatory T cells and competing elements of the immune system ('cytokine sinks'). Newly emerging animal data suggest that more profound lymphoablative conditioning with autologous hematopoetic stem-cell rescue might further enhance treatment results. Here we review recent advances in adoptive immunotherapy of solid tumors and discuss the rationale for lymphodepleting conditioning. We also address safety issues associated with translating experimental animal results of total lymphoid ablation into clinical practice. Review criteriaThe PubMed and MEDLINE databases were searched for articles published until April 2006. Electronic early-release publications were also included. Only articles published in English were considered. The search terms used included "adoptive cell transfer", "lymphodepletion", "lymphopenia", "TBI", "homeostatic proliferation", "allogeneic transplant", "syngeneic transplant", "IPS" and "treatment related mortality". Full articles were obtained and references were checked for additional material when appropriate. References were chosen based on the best clinical or laboratory evidence, especially if data had been corroborated by published work from other centers. Priority was given to studies in high-impact-factor journals when available.

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“…Como relatado no site, resultados animadores obtidos com os primeiros 20 pacientes levaram à extensão do estudo para pacientes com esclerodermia difusa precoce com marcadores de mau prognóstico. Protocolos semelhantes, patrocinados pelo NIH, foram planejados nos EUA, mas não há consenso entre os vários grupos sobre o melhor regime de condicionamento (com ou sem irradiação corporal total) (64) .…”

Section: Esclerose Sistêmicaunclassified

Transplante de células-tronco hematopoéticas em doenças reumáticas parte 1: experiência internacional

Voltarelli¹,

Stracieri²,

Soga³

et al. 2005

Rev. Bras. Reumatol.

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RESUMONesta revisão, discutem-se os resultados dos transplantes de células-tronco hematopoéticas (TCTH) para doenças reumáticas graves e refratárias à terapia convencional realizados no exterior. Revêem-se brevemente as bases clínicas e experimentais para a realização desses transplantes e os resultados internacionais obtidos em lúpus eritematoso sistêmico (LES) (33/50 remissões completas no registro europeu, com dez recidivas posteriores e 12 óbitos; 41/45 remissões duradouras em um centro americano, com dois óbitos pós-mobilização e quatro óbitos pós-transplante), artrite reumatóide (AR) do adulto (58/73 remissões parciais com 85% de recidivas posteriores e apenas um óbito no registro europeu), artrite idiopática juvenil (AIJ) (18/34 remissões duradouras e cinco óbitos no registro europeu), esclerose sistêmica (ES) (46/50 respostas em um estudo europeu multicêntrico, com 35% de recidivas e 23% de mortalidade, enquanto num estudo americano, houve quatro óbitos e duas pneumopatias progressivas dentre 19 pacientes e melhora cutânea e da qualidade de vida em todos os sobreviventes) e em uma miscelânea de outras doenças, incluindo as vasculites (9/15 respostas completas no registro europeu). Conclui-se que, na experiência internacional, o TCTH autólogo induz remissões prolongadas na maioria das doenças graves e refratárias em que foi utilizado, com exceção da AR do adulto, justificando o início de estudos prospectivos randomizados comparando-o com a terapia convencional otimizada.

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The rationale behind autologous autoimmune hematopoietic stem cell transplant conditioning regimens: concerns over the use of total-body irradiation in systemic sclerosis

Cited by 26 publications

References 57 publications

Autologous non-myeloablative hematopoietic stem cell transplantation in patients with systemic sclerosis

Autologous non-myeloablative hematopoietic stem cell transplantation in patients with systemic sclerosis

Increased intensity lymphodepletion and adoptive immunotherapy—how far can we go?

Transplante de células-tronco hematopoéticas em doenças reumáticas parte 1: experiência internacional

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