Early recurrence or persistence of autoimmune diseases after unmanipulated autologous stem cell transplantation

Euler, H. H.; Marmont, A; Bacigalupo, Andrea; Fastenrath, Sven; Dreger, Peter; Hoffknecht, M.; Zander, Axel R.; Schalke, Berthold; Hahn, Uwe; Haas, Rainer; Schmitz, Norbert

doi:10.1182/blood.v88.9.3621.bloodjournal8893621

Cited by 194 publications

(50 citation statements)

References 19 publications

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“…Early data from autologous HSCT for RA and other autoimmune diseases are gradually appearing in the literature (Joske et al, 1997;Lim et al, 1997;Fassas et al, 1997;Marmont et al, 1997;Burt et al, 1997; Snowden et al, 1998c). However, in contrast to data on allogeneic HSCT (Snowden et al, 1998b), it is unlikely that autografting in its present form will represent a cure, as relapse occurs after a variable period of time Euler et al, 1996). Graft manipulation provides one of several avenues for clinical trials aimed at improving responses and remissions.…”

Section: Discussionmentioning

confidence: 99%

Composition and function of peripheral blood stem and progenitor cell harvests from patients with severe active rheumatoid arthritis

Snowden¹,

Nink²,

Cooley³

et al. 1998

Br J Haematol

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High-dose chemotherapy with autologous stem cell rescue has been proposed as an intensive therapy for severe rheumatoid arthritis (RA). In view of previous observations of abnormal haemopoiesis in RA patients, the composition and function of peripheral blood stem cell harvests (PBSCH) was investigated. Compared with PBSCH from healthy allogeneic donors mobilized with the same dose of G-CSF (filgrastim; 10 microg/kg/d, n = 14), RA PBSCH (n = 9) contained significantly fewer mononuclear cells (375 v 569 x 10(6)/kg, P = 0.03) and CD34+ cells (2.7 v 5.8 x 10(6)/kg, P = 0.003). However, there were increased proportions of CD14+ cells (P = 0.006) and CD14+ CD15+ cells (the phenotype of previously described 'abnormal' myeloid cells, P = 0.002) in the RA PBSCH which translated into 3.5- and 7-fold increases respectively on a per CD34+ cell basis. There were no differences in T-cell activation status as judged by proportions of CD4+ and CD8+ expressing CD45RA, CD45RO, HLA-DR and CD28 (RA PBSCH, n = 7, donor PBSCH, n = 5, P = 0.2-0.7). Phytohaemagglutinin responses determined fluorocytometrically with induction of CD69 expression were reduced in CD4+ and CD8+ cells following filgrastim administration in 3/3 RA patients tested. Compared with bone marrow as a potential source of CD34+ cells, PBSCH contained 11-fold more T cells (P < 0.0005), 8-fold more B cells (P < 0.0005) and 4-fold more monocytes (P = 0.02). In short-term methylcellulose culture there were no differences in colony counts (CFU-GM, CFU-GEMM, BFU-E) per CD34+ cell from PBSCH from RA patients (n = 11) and healthy donors (n = 10). Long-term culture initiator cells were cultured successfully from cryopreserved PBSCH from RA patients (n = 9). In conclusion, PBSCH from RA patients differed significantly in composition from normal individuals, but in vitro studies support normal stem and progenitor cell function. Changes in T-cell function occur during mobilization in RA patients. This work provides reassurance for the use of PBSCH as haematological rescue and baseline data for clinical trials of graft manipulation strategies in patients with RA.

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Section: Discussionmentioning

confidence: 99%

Composition and function of peripheral blood stem and progenitor cell harvests from patients with severe active rheumatoid arthritis

Snowden¹,

Nink²,

Cooley³

et al. 1998

Br J Haematol

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“…Peripheral blood stem cells were mobilized with cyclophosphamide (CY, 4 gr/m 2 ) and treated with conditioning regimen consisting of BEAM. 16 More recently, in six cases, a "lighter" protocol was utilized, with SC mobilization carried out with CY 120 mg/kg and CY 120 mg/kg and ATG as conditioning protocol. One case treated with CY and BEAM died after 70 days from transplantation of a cerebral hemorrhage due to fibrinolytic therapy initiated for an asymptomatic pulmonary embolism.…”

Section: Msmentioning

confidence: 99%

Autologous Stem Cell Transplantation for Severe Autoimmune Diseases

Gualandi¹,

Bruno²,

Lint³

et al. 2007

Annals of the New York Academy of Sciences

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The first autologous hematopoietic stem cell transplantation in Europe for a patient with severe refractory systemic lupus erythematosus (SLE) was performed in Genoa in 1996. Since then, 32 patients with a wide spectrum of autoimmune diseases (ADs) received autologous transplants, 22 of them with multiple sclerosis (MS). There were no fatal adverse events. All patients had complete or very good partial remissions, but relapses were frequent, especially in SLE, though never as aggressive as pretransplant. The mechanism of action of this intervention remains not completely understood, as briefly discussed here.

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“…Autologous transplantation in our patient was unsuccessful and the lack of a prolonged remission may be due to survival of autoaggressive lymphoid clones, reinfusion of these clones, or a new challenge of the regenerating immune system by recipient autoantigens (Euler et al, 1996). In contrast, the success of allogeneic BMT may be explained by both the direct chemotherapy-induced ablation of recipient immune system and a graft-versus-autoimmunity effect (similar to the graft-versus-leukaemia effect in patients with malignancies) played by donor lymphocytes towards recipient autoaggressive clones.…”

Section: Discussionmentioning

confidence: 78%

Resolution of immune haemolytic anaemia with allogeneic bone marrow transplantation after an unsuccessful autograft

et al. 1999

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Autologous transplantation of lymphocyte‐depleted peripheral blood stem cells (PBSC) has been proposed for treatment of patients with severe autoimmune disease. However, several patients have been reported to achieve only transient remissions. We report on a child with thalassaemia intermedia and immune‐mediated haemolytic anaemia, given an autologous lymphocyte‐depleted PBSC transplant, who relapsed 7 weeks after transplant. A complete remission, lasting 18 months to date, was obtained with allogeneic bone marrow transplantation (BMT) from an HLA‐matched unrelated donor. This experience indicates that, in selected cases, allogeneic BMT may be the treatment of choice for life‐threatening autoimmune disease. A graft‐versus‐autoimmunity effect may favour the eradication of the recipient autoaggressive lymphocytes.

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Early recurrence or persistence of autoimmune diseases after unmanipulated autologous stem cell transplantation

Cited by 194 publications

References 19 publications

Composition and function of peripheral blood stem and progenitor cell harvests from patients with severe active rheumatoid arthritis

Composition and function of peripheral blood stem and progenitor cell harvests from patients with severe active rheumatoid arthritis

Autologous Stem Cell Transplantation for Severe Autoimmune Diseases

Resolution of immune haemolytic anaemia with allogeneic bone marrow transplantation after an unsuccessful autograft

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