Autologous marrow stem cell transplantation for severe systemic lupus erythematosus of long duration

Am, Marmont; Lint, MT Van; Gualandi, Francesca; Bacigalupo, Andrea

doi:10.1177/096120339700600613

Cited by 152 publications

(93 citation statements)

References 5 publications

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“…If human SLE is also triggered by the hormonal and environmental milieu in a genetically susceptible host, then high-dose chemotherapy and HSCT should also induce sustained lupus-free remissions. (1) in Genoa, Italy. That same year, our group of investigators began performing HSCT for SLE in the US (2)(3)(4)(5).…”

Section: Hematopoietic Stem Cell Transplantation (Hsct)mentioning

confidence: 99%

Hematopoietic stem cell transplantation for severe and refractory lupus

Traynor¹,

Barr²,

Rosa³

et al. 2002

Arthritis & Rheumatism

116

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Objective. To determine the safety and long-term efficacy of immune ablation and autologous hematopoietic stem cell transplantation (HSCT) in severe systemic lupus erythematosus (SLE).Methods. Fifteen patients with persistently active SLE after intravenous (IV) cyclophosphamide (CYC) therapy underwent HSCT. Stem cells were mobilized with CYC (2.0 gm/m 2 ) and granulocyte colonystimulating factor (5 g/kg/day). Lymphocytes were depleted from the graft by selection of CD34-positive cells. The conditioning regimen used was CYC (200 mg/kg), antithymocyte globulin (90 mg/kg), and methylprednisolone (3 mg/kg). Outcome was evaluated by the SLE Disease Activity Index (SLEDAI), serum complement levels, serologic features, function of diseased organs, and immunosuppressive medication requirements.Results. Fifteen patients with persistent, severe SLE, 7 of whom were critically ill, were treated. No deaths occurred following treatment. The median followup after HSCT has been 36 months (range 12-66 months). All patients demonstrated a gradual, but marked, improvement. The SLEDAI score has declined to <5 in 12 patients. Complement and anti-doublestranded DNA levels have normalized and marked improvements in end organ function have occurred in all subjects. Of the 12 patients followed up for >1 year after HSCT, 10 have discontinued immunosuppressive medications, and the prednisone dosage has been tapered to 15 mg/day in 1. Only 2 patients have demonstrated clinical evidence of recurrence of active lupus. One of these patients currently requires no immunosuppressive medication and has a normal performance status. The other patient is currently receiving IV CYC.Conclusion. In patients experiencing the persistence of organ-threatening lupus following standard, aggressive therapy, HSCT may be performed safely, with marked improvement and sustained withdrawal of all immunosuppressive medication for most patients. A phase III randomized trial is warranted to determine the relative efficacy and durability of remission of HSCT compared with standard therapies. Hematopoietic stem cell transplantation (HSCT)is most commonly applied to chemotherapy-sensitive "malignant" hematologic diseases, such as lymphoma or multiple myeloma. These malignancies are characterized by invasive or injurious clonal or oligoclonal lymphocyte proliferation. Diseases for which autologous stem cell transplants are used successfully are believed to be environmentally induced in a setting of genetic susceptibility. HSCT allows for normal, healthy hematopoietic stem cells to repopulate the bone marrow and peripheral blood after chemotherapy-induced elimination of the malignant clones. It may be anticipated that disease-mediating lymphocytes in patients with systemic lupus erythematosus (SLE) should be at least as prone to therapeutic eradication as malignant lymphocytes. If human SLE is also triggered by the hormonal and environmental milieu in a genetically susceptible host, then high-dose chemotherapy and HSCT should also induce sustained lupus-free remissions.

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Section: Hematopoietic Stem Cell Transplantation (Hsct)mentioning

confidence: 99%

Hematopoietic stem cell transplantation for severe and refractory lupus

Traynor¹,

Barr²,

Rosa³

et al. 2002

Arthritis & Rheumatism

116

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“…Clinical evidence supports the idea that it is probably just the absolute ablation of the pathological clone through cytotoxic drugs which is responsible for clinical improvement or cure, as complete responses have been described for different autoimmune disorders with ABMT. 8,9,[11][12][13] ABMT is beginning to be considered an acceptable choice of treatment for patients with severe forms of autoimmune diseases. It is difficult to decide which patients should be considered candidates for this therapeutic approach.…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, several authors have described selected cases in which, because of their severity, ABMT has been performed in these pathologies. [11][12][13] On the other hand, transferral of MG, 14 AT 15 and some autoimmune phenomena of SLE 16 from donors to recipients of a BMT has also been described, as if there were a direct correspondence between the activity of the disease and marrow immunocompetent cells.…”

mentioning

confidence: 99%

Disappearance of lupus anticoagulant after allogeneic bone marrow transplantation

Olalla

Ortín

Hermida

et al. 1998

Bone Marrow Transplant

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Summary:Lupus anticoagulant antibodies have never been reported to disappear after either allogeneic or autologous bone marrow transplantation in humans. We report the first case of disappearance of lupus anticoagulant antibodies in a patient without systemic lupus erythematosus or clinical evidence of other autoimmune disorders, who received an allogeneic bone marrow transplant as treatment for chronic myeloid leukemia. Although marrow transplantation is not a recognized therapy for antiphospholipid syndrome, our observation should be considered another example of the capability of intensive chemo-radiotherapy followed by stem cell transplantation to ablate a pathologic marrow clone resulting in an autoimmune disorder and improve, or even cure, some severe autoimmune diseases.

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“…The next major advance in treating lupus may have occurred when cyclophosphamide was dose escalated to highly immune-suppressive transplant doses of 200 mg/kg and combined with antithymocyte globulin (ATG) and hematopoietic stem cell reinfusion, beginning in 1996. [1][2][3] Patients were selected for active disease refractory to monthly intravenous cyclophosphamide. Ongoing visceral organ dysfunction, provided it was secondary to active SLE, was an indication for hematopoietic stem cell transplantation (HSCT).…”

mentioning

confidence: 99%

“…1,20 Be that as it may, clinical results are encouraging and even dramatic in properly selected patients. Some of the best results are being obtained in SLE, juvenile idiopathic arthritis, Crohn's disease, and in active MS, where the abrogation of all gadolinium-enhancing lesions has been reported on serial post-transplant MRIs.…”

mentioning

confidence: 99%