Immunoablative High-Dose Cyclophosphamide without Stem-Cell Rescue for Refractory, Severe Autoimmune Disease

Brodsky, Robert A.; Petri, Michelle; Smith, B. Douglas; Seifter, Eli; Spivak, Jerry L.; Styler, Michael; Dang, Chi V.; Brodsky, Isadore; Jones, Richard J.

doi:10.7326/0003-4819-129-12-199812150-00007

Cited by 226 publications

(124 citation statements)

References 15 publications

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“…[1][2][3][4][5]13,14 Experiments on animal models and the effect of myeloablative-immunoablative treatment in patients with concomitant haematological and autoimmune disease (AID) constitute the background for such a new approach. [15][16][17][18][19][20][21][22][23][24] Based on animal models and experience in humans, allogeneic haematopoietic cell transplantation would represent the best option to cure poor risk AID.…”

Section: Discussionmentioning

confidence: 99%

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High-dose immunosuppressive therapy with PBPC support in the treatment of poor risk multiple sclerosis

Kozák

Havrdová

Piťha

et al. 2000

Bone Marrow Transplant

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Summary:High-dose immunoablative chemotherapy with autologous haematopoietic cell support might be beneficial in the treatment of intractable forms of MS. We mobilised PBPC in 11 patients with secondary progressive MS and finally eight patients were grafted after high-dose BEAM chemotherapy with either in vitro or in vivo T cell depletion. Median EDSS and SNRS scores at the time of inclusion were 6.5 (6.5-7.5) and 56 (44-65), respectively. PBPC mobilisation was safe with no serious adverse effects, and without significant aggravation of disability.

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Section: Discussionmentioning

confidence: 99%

“…None of the patients had positive blood cultures. The median number of days spent in hospital was 15 (range [13][14][15][16][17][18][19][20][21][22][23][24][25][26]. Mobilisation course and results are shown in Table 2.…”

Section: Stem Cell Mobilisation and Harvestmentioning

confidence: 99%

High-dose immunosuppressive therapy with PBPC support in the treatment of poor risk multiple sclerosis

Kozák

Havrdová

Piťha

et al. 2000

Bone Marrow Transplant

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“…8,9 Hematopoietic SCT (HSCT) for treatment of severe autoimmune diseases is being explored as therapy for various immune-mediated diseases, 10,11 as well as the utilization of high-dose chemotherapy without stem cell rescue. [12][13][14][15] Nevertheless, the exact immunological mechanisms by which BM cells (BMCs) or high-dose immunosuppression provide remission for those diseases, including IBD, is not yet clear. [16][17][18][19][20] Moreover, the success of patient trials depends largely on the elucidation of the cellular mechanisms involved in the pathogenesis and outcome of the disease after HSCT, which are not fully provided by the studies with human subjects, but can be achieved with animal studies.…”

Section: Introductionmentioning

confidence: 99%

Hematopoietic SCT modulates gut inflammation in experimental inflammatory bowel disease

Godoi

Cardoso

Ferraz

et al. 2010

Bone Marrow Transplant

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Hematopoietic SCT (HSCT) and high-dose chemotherapy are being explored as therapy for various human refractory immune-mediated conditions, including inflammatory bowel diseases (IBD). Nevertheless, the exact immunological mechanisms by which the BM cells (BMCs) or immunosuppression provide remission from these diseases is not yet clear. In this work, we investigated the role of these therapies in the modulation of gut mucosal inflammation in an experimental model of IBD. Colitis was induced in mice by 2,4,6-trinitrobenzenesulfonic acid and after CY was administered (200 mg/kg) alone (CY group) or followed by BMCs infusion (HSCT group). Animals were followed for 60 days. Both HSCT and CY reduced the histopathological features of colitis significantly. Infused cells were localized in the gut, and a marked decrease of CD4 þ leukocytes in the inflammatory infiltrate on days þ 7 and þ 14 and of CD8 þ cells on day þ 7 was found in both treatments allied to impressive reduction of proinflammatory Th1 and Th17 cytokines. Although chemotherapy alone was the best treatment regarding the induction of immunosuppressive molecules, only HSCT resulted in increased survival rates compared with the control group. Our findings indicate that highdose CY followed by HSCT is effective in the modulation of mucosal immunity and in accelerating immune reconstitution after BMT, thus providing valuable tools to support the development and understanding of novel therapeutic strategies for IBD.

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“…A primeira evidência clínica do possível benefício da imunossupressão maciça sobre a evolução de DAI grave não associada a hemopatias foi publicada em 1993, sendo o relato de uma paciente acometida de crioglobulinemia mista com nefrite e vasculite, que obteve remissão prolongada após quimioterapia em altas doses sem infusão de CTH (14) e não. Resultados semelhantes têm sido relatados pelo grupo da Johns Hopkins University (Baltimore, EUA) no LES e em outras DAIs, utilizando doses imunoablativas de ciclofosfamida (CY, 200 mg/kg) sem resgate de CTH (15,16) . Entretanto, este esquema produz um período relativamente prolongado de pancitopenia (média de 14 dias, variando de 11 a 22 dias no LES) e foi associado a significativa mortalidade quando aplicado à anemia aplástica no National Institutes of Health (NIH) americano (17) , levando à interrupção do protocolo.…”

Section: Bases Científicas Para O Tratamento De Doenças Auto-imunes Cunclassified

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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Immunoablative High-Dose Cyclophosphamide without Stem-Cell Rescue for Refractory, Severe Autoimmune Disease

Cited by 226 publications

References 15 publications

High-dose immunosuppressive therapy with PBPC support in the treatment of poor risk multiple sclerosis

High-dose immunosuppressive therapy with PBPC support in the treatment of poor risk multiple sclerosis

Hematopoietic SCT modulates gut inflammation in experimental inflammatory bowel disease

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

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