Immunotherapy of Familial Hemophagocytic Lymphohistiocytosis With Antithymocyte Globulins: A Single-Center Retrospective Report of 38 Patients

• Published in: Pediatrics (Evanston) 2007-09, Vol.120 (3), p.e622-e628
• Main Authors: Mahlaoui, Nizar, Ouachee-Chardin, Marie, de Saint Basile, Genevieve, Neven, Benedicte, Picard, Capucine, Blanche, Stephane, Fischer, Alain
• Format: Article
• Language: English
• Subjects: Adrenal Cortex Hormones - therapeutic use; Antilymphocyte Serum - therapeutic use; Babies; Child; Child, Preschool; Cyclosporine - therapeutic use; Drug Therapy, Combination; Female; Hematopoietic Stem Cell Transplantation; Humans; Immune system; Immunoglobulins; Immunosuppressive Agents - therapeutic use; Immunotherapy; Infection - complications; Infection - etiology; Injections, Spinal; Lymphocytes; Lymphohistiocytosis, Hemophagocytic - mortality; Lymphohistiocytosis, Hemophagocytic - therapy; Lymphoproliferative Disorders - etiology; Male; Methotrexate - therapeutic use; Methylprednisolone - therapeutic use; Pediatrics; Recurrence; Retrospective Studies; Treatment Outcome
• ISSN: 0031-4005; 1098-4275
• DOI: 10.1542/peds.2006-3164

Familial hemophagocytic lymphohistiocytosis is a genetically determined condition that is characterized by unremitting CD8 T lymphocyte and macrophage activation and leads to death in the absence of therapy. On the basis of the immunologic pathophysiology of familial hemophagocytic lymphohistiocytosis, we propose a therapy with a combination of antithymocyte globulins with corticosteroids, cyclosporin A, and intrathecal injections of methotrexate. We retrospectively analyzed the outcome of antithymocyte globulin-based therapy that was performed in 38 consecutive patients who had familial hemophagocytic lymphohistiocytosis and were treated in a single center between 1991 and 2005. Overall, they received 45 courses of antithymocyte globulin (5-10 mg/kg per day for 5 days). This regimen was associated with infections after 10 of 45 courses of antithymocyte globulin. There were 6 events after 11 antithymocyte globulin courses given as second-line therapy against 4 after 34 antithymocyte globulin courses in patients who were treated primarily with antithymocyte globulin. Antithymocyte globulin administration led to rapid and complete response of familial hemophagocytic lymphohistiocytosis in 73% of cases, partial response in 24%, and no response only once. When hematopoietic stem cell transplantation was performed early after complete or partial response induction, it led to a high rate of cure, in 16 of 19 cases. Overall survival was 21 of 38 with 4 toxic deaths. Antithymocyte globulin based immunotherapy of familial hemophagocytic lymphohistiocytosis is efficient and carries an acceptable toxicity when used as a first treatment of familial hemophagocytic lymphohistiocytosis.