title: Allogeneic Hematopoietic Stem Cell Transplantation in the Treatment of Human C1q Deficiency: The Karolinska Experience.
abstract: Human C1q deficiency is associated with systemic lupus erythematosus (SLE) and increased susceptibility to severe bacterial infections. These patients require extensive medical therapy and some develop treatment-resistant disease. Because C1q is produced by monocytes, it has been speculated that allogeneic hematopoietic stem cell transplantation (allo-HSCT) may cure this disorder.
  
  
  
  We have so far treated 5 patients with C1q deficiency. In 3 cases, SLE symptoms remained relatively mild after the start of medical therapy, but 2 patients developed treatment-resistant SLE, and we decided to pursue treatment with allo-HSCT. For this purpose, we chose a conditioning regimen composed of treosulfan (14 g/m) and fludarabine (30 mg/m) started on day -6 and given for 3 and 5 consecutive days, respectively. Thymoglobulin was given at a cumulative dose of 8 mg/kg, and graft-versus-host disease prophylaxis was composed of cyclosporine and methotrexate.
  
  
  
  A 9-year-old boy and a 12-year-old girl with refractory SLE restored C1q production after allo-HSCT. This resulted in normal functional properties of the classical complement pathway followed by reduced severity of SLE symptoms. The boy developed posttransplant lymphoproliferative disease, which resolved after treatment with rituximab and donor lymphocyte infusion. Unfortunately, donor lymphocyte infusion induced severe cortisone-resistant gastrointestinal graft-versus-host disease, and the patient died from multiple organ failure 4 months after transplantation. The girl is doing well 33 months after transplantation, and clinically, all signs of SLE have resolved.
  
  
  
  Allo-HSCT can cure SLE in human C1q deficiency and should be considered early in subjects resistant to medical therapy.
authors.affiliation: 1 Centre for Allogeneic Stem Cell Transplantation, Karolinska University Hospital, Huddinge, Sweden. 2 Division of Therapeutic Immunology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden. 3 Centre for Clinical Research Sörmland, Uppsala University, Uppsala, Sweden. 4 Department of Paediatrics, Karolinska University Hospital, Stockholm, Sweden. 5 Department of Clinical Science and Education, Karolinska Institutet, Södersjukhuset, Sachs' Children's and Youth Hospital, Stockholm, Sweden. 6 Section of Microbiology, Immunology and Glycobiology, Department of Laboratory Medicine, Lund University, Lund, Sweden.
authors.forename: Richard F
authors.initials: RF
authors.lastname: Olsson
authors.forename: Stefan
authors.initials: S
authors.lastname: Hagelberg
authors.forename: Bodil
authors.initials: B
authors.lastname: Schiller
authors.forename: Olle
authors.initials: O
authors.lastname: Ringdén
authors.forename: Lennart
authors.initials: L
authors.lastname: Truedsson
authors.forename: Anders
authors.initials: A
authors.lastname: Åhlin
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D015922:Complement C1q / Q000172:deficiency*; D003348:Cortisone / Q000009:adverse effects; D016572:Cyclosporine / Q000008:administration & dosage; D017809:Fatal Outcome; D005260:Female; D005767:Gastrointestinal Diseases / Q000209:etiology / Q000401:mortality; D006086:Graft vs Host Disease / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006579:Heterozygote; D006801:Humans; D007223:Infant; D007493:Iraq; D008180:Lupus Erythematosus, Systemic / Q000628:therapy*; D008232:Lymphoproliferative Disorders / Q000209:etiology; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D011183:Postoperative Complications; D000069283:Rituximab / Q000008:administration & dosage; D013548:Sweden; D013997:Time Factors; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D000069283:Rituximab; D015922:Complement C1q; D016572:Cyclosporine; D003348:Cortisone; D008727:Methotrexate