Hematopoietic stem cell transplantation for severe and refractory lupus. Analysis after five years and fifteen patients.

Abstract

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 colony-stimulating factor (5 microg/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 <or=5 in 12 patients. Complement and anti-double-stranded 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.

• Authors: Ann E Traynor, Walter G Barr, Robert M Rosa, Julianne Rodriguez, Yu Oyama, Steven Baker, Mary Brush, Richard K Burt
• Journal: Arthritis and rheumatism (Arthritis Rheum) Vol. 46 Issue 11 Pg. 2917-23 (Nov 2002) ISSN: 0004-3591 [Print] United States
• PMID: 12428232 (Publication Type: Journal Article)

Chemical References

• Immunosuppressive Agents
• Prednisolone

Topics

• Adolescent
• Adult
• Female
• Follow-Up Studies
• Hematopoietic Stem Cell Transplantation
• Humans
• Immunosuppressive Agents (administration & dosage)
• Lupus Erythematosus, Systemic (therapy)
• Male
• Prednisolone (administration & dosage)
• Safety
• Transplantation Conditioning
• Treatment Outcome