Immune ablation followed by allogeneic or autologous bone marrow transplantation: A new treatment for severe autoimmune diseases?

Marmont, A

doi:10.1002/stem.5530120119

Cited by 99 publications

(56 citation statements)

References 66 publications

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“…A register of patients with autoimmune diseases undergoing BMT would be a first step in developing rational patient selection guidelines and followup protocols (20). Certainly the potential of BMT as a treatment modality in severe RA and other autoimmune diseases needs to be further evaluated (21).…”

Section: Discussionmentioning

confidence: 99%

Progression of rheumatoid arthritis following bone marrow transplantation. A case report with a 13‐year followup

Mckendry

Huebsch

Leclair

1996

Arthritis & Rheumatism

117

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The progression of rheumatoid arthritis (RA) is documented in a patient receiving a sex‐mismatched, allogeneic bone marrow transplant (BMT) for gold‐induced marrow aplasia. DNA typing confirmed a high probability of a full donor engraftment (complete chimerism). Although the RA was in complete remission 2 years post‐BMT, clinical, laboratory, histologic, and radiologic evidence of the recurrence of synovitis from 3–13 years post‐BMT is presented. Implications of these observations for theories of the pathogenesis of RA and the future of immunotherapies are discussed.

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Section: Discussionmentioning

confidence: 99%

Progression of rheumatoid arthritis following bone marrow transplantation. A case report with a 13‐year followup

Mckendry

Huebsch

Leclair

1996

Arthritis & Rheumatism

117

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“…[1][2][3][4][5][6] These findings have recently been confirmed even in humans. [7][8][9][10][11][12][13][14][15] However, in humans, the success rate of BMT across major histocompatibility complex (MHC) barriers is lowered by graft-versus-host disease (GVHD), graft rejection, and incomplete T-cell recovery. Therefore, autologous BMT (auto BMT) or peripheral blood stem cell transplantation (auto PBSCT) is the preferred treatment for autoimmune diseases.…”

Section: Introductionmentioning

confidence: 99%

Intra–bone marrow injection of allogeneic bone marrow cells: a powerful new strategy for treatment of intractable autoimmune diseases in MRL/lpr mice

Kushida

Inaba

Hisha

et al. 2001

Blood

246

309

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Intractable autoimmune diseases in chimeric resistant MRL/lpr mice were treated by a new bone marrow transplantation (BMT) method consisting of fractionated irradiation, 5.5 Gy ؋ 2, followed by intrabone marrow (IBM) injection of whole bone marrow cells (BMCs) from allogeneic normal C57BL/6 (B6) mice (5.5 Gy ؋ 2 ؉ IBM). In MRL/lpr mice treated with this method, the number of donor-derived cells in the bone marrow, spleen, and liver rapidly increased (almost 100% donor-derived cells by 14 days after the treatment), and the number of donorderived hemopoietic progenitor cells concomitantly increased. Furthermore, donorderived stromal cells were clearly detected in the cultured bone pieces from MRL/lpr mice treated with 5.5 Gy ؋ 2 ؉ IBM. All the recipients thus treated survived more than 1 year (> 60 weeks after birth) and remained free from autoimmune diseases. Autoantibodies decreased to almost normal levels, and abnormal T cells (

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“…[1][2][3][4][5][6][7][8][9] Recent advances, including the use of cytokine mobilised peripheral blood stem cells, have resulted in major reductions in the mortality and morbidity of autologous transplantation for malignant diseases 10,11 and it now seems reasonable to consider HSCT as an experimental treatment for severe autoimmune diseases.…”

mentioning

confidence: 99%

A randomised, blinded, placebo-controlled, dose escalation study of the tolerability and efficacy of filgrastim for haemopoietic stem cell mobilisation in patients with severe active rheumatoid arthritis

Snowden

Biggs

Milliken

et al. 1998

Bone Marrow Transplant

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Summary:Autologous haemopoietic stem cell transplantation (HSCT) represents a potential therapy for severe rheumatoid arthritis (RA). As a prelude to clinical trails, the safety and efficacy of haemopoietic stem cell (HSC) mobilisation required investigation as colony-stimulating factors (CSFs) have been reported to flare RA. A double-blind, randomised placebo-controlled dose escalation study was performed. Two cohorts of eight patients fulfilling strict eligibility criteria for severe active RA (age median 40 years, range 24-60 years; median disease duration 10.5 years, range 2-18 years) received filgrastim (r-Hu-methionyl granulocyte(G)-CSF) at 5 and 10 g/kg/day, randomised in a 5:3 ratio with placebo. Patients were unblinded on the fifth day of treatment and those randomised to filgrastim underwent cell harvesting (leukapheresis) daily until 2 ؋ 10 6 /kg CD34 ؉ cells (haemopoietic stem and progenitor cells) were obtained. Patients were assessed by clinical and laboratory parameters before, during and after filgrastim administration. RA flare was defined as an increase of 30% or more in two of the following parameters: tender joint count, swollen joint count or pain score. Efficacy was assessed by quantitation of CD34 ؉ cells and CFU-GM. One patient in the 5 g/kg/day group and two patients in the 10 g/kg/day group fulfilled criteria for RA flare, although this did not preclude successful stem cell collection. Median changes in swollen and tender joint counts were not supportive of filgrastim consistently causing exacerbation of disease, but administration of filgrastim at 10 g/kg/day was associated with rises in median C-reactive protein and median rheumatoid factor compared with placebo. Other adverse events were well recognised for filgrastim and included bone pain (80%) and increases in alkaline phosphatase (four-fold) and lactate dehydrogenase (two-fold). With respect to efficacy, filgrastim at 10 g/kg/day was more efficient with all patients (n = 5) achieving target CD34 ؉ cell counts with a single leuCorrespondence: Dr JA Snowden, Department of Haematology, Royal Hallamshire Hospital, Sheffield S10 2JF, UK Received 2 May 1998; accepted 21 July 1998 kapheresis (median = 2.8, range = 2.3-4.8 ؋ 10 6 /kg, median CFU-GM = 22.1, range = 4.2-102.9 ؋ 10 4 /kg), whereas 1-3 leukaphereses were necessary to achieve the target yield using 5 g/kg/day. We conclude that filgrastim may be administered to patients with severe active RA for effective stem cell mobilisation. Flare of RA occurs in a minority of patients and is more likely with 10 than 5 g/kg/day. However, on balance, 10 g/kg/day remains the dose of choice in view of more efficient CD34 ؉ cell mobilisation.

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Immune ablation followed by allogeneic or autologous bone marrow transplantation: A new treatment for severe autoimmune diseases?

Cited by 99 publications

References 66 publications

Progression of rheumatoid arthritis following bone marrow transplantation. A case report with a 13‐year followup

Progression of rheumatoid arthritis following bone marrow transplantation. A case report with a 13‐year followup

Intra–bone marrow injection of allogeneic bone marrow cells: a powerful new strategy for treatment of intractable autoimmune diseases in MRL/lpr mice

A randomised, blinded, placebo-controlled, dose escalation study of the tolerability and efficacy of filgrastim for haemopoietic stem cell mobilisation in patients with severe active rheumatoid arthritis

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