Immunotherapy of familial hemophagocytic lymphohistiocytosis with antithymocyte globulins: a single-center retrospective report of 38 patients.
OBJECTIVE
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.


METHODS
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).


RESULTS
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.


CONCLUSIONS
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.
Mahlaoui
Nizar
N
Unité d'Immunologie et Hématologie Pédiatrique, Hôpital Necker-Enfants Malades, 149 rue de Sèvres, 75015 Paris, France.
Ouachée-Chardin
Marie
M
de Saint Basile
Geneviève
G
Neven
Bénédicte
B
Picard
Capucine
C
Blanche
Stéphane
S
Fischer
Alain
A
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007167:Immunotherapy; D007239:Infections / Q000150:complications / Q000209:etiology; D007278:Injections, Spinal; D051359:Lymphohistiocytosis, Hemophagocytic / Q000401:mortality / Q000628:therapy*; D008232:Lymphoproliferative Disorders / Q000209:etiology; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008775:Methylprednisolone / Q000627:therapeutic use; D012008:Recurrence; D012189:Retrospective Studies; D016896:Treatment Outcome
D000305:Adrenal Cortex Hormones; D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D008775:Methylprednisolone; D008727:Methotrexate