Use of rituximab for refractory cytopenias associated with autoimmune lymphoproliferative syndrome (ALPS)

Pediatr Blood Cancer. 2009 Jul;52(7):847-52. doi: 10.1002/pbc.21965.


Background: ALPS is a disorder of apoptosis resulting in accumulation of autoreactive lymphocytes, leading to marked lymphadenopathy, hepatosplenomegaly, and multilineage cytopenias due to splenic sequestration and/or autoimmune destruction often presenting in childhood. We summarize our experience of rituximab use during the last 8 years in 12 patients, 9 children, and 3 adults, out of 259 individuals with ALPS, belonging to 166 families currently enrolled in studies at the National Institutes of Health.

Methods: Refractory immune thrombocytopenia (platelet count <20,000) in nine patients and autoimmune hemolytic anemia (AIHA) in three patients led to treatment with rituximab. Among them, seven patients had undergone prior surgical splenectomy; three had significant splenomegaly; and two had no palpable spleen.

Results: In seven out of nine patients with ALPS and thrombocytopenia, rituximab therapy led to median response duration of 21 months (range 14-36 months). In contrast, none of the three children treated with rituximab for AIHA responded. Noted toxicities included profound and prolonged hypogammaglobulinemia in three patients requiring replacement IVIG, total absence of antibody response to polysaccharide vaccines lasting up to 4 years after rituximab infusions in one patient and prolonged neutropenia in one patient.

Conclusion: Toxicities including hypogammaglobulinemia and neutropenia constitute an additional infection risk burden, especially in asplenic individuals, and may warrant avoidance of rituximab until other immunosuppressive medication options are exhausted. Long-term follow-up of ALPS patients with cytopenias after any treatment is necessary to determine relative risks and benefits.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adolescent
  • Adult
  • Anemia, Hemolytic, Autoimmune / drug therapy*
  • Anemia, Hemolytic, Autoimmune / immunology
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Murine-Derived
  • Autoimmune Diseases / drug therapy*
  • Autoimmune Diseases / immunology
  • Child
  • Child, Preschool
  • Drug Resistance, Neoplasm
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Infant
  • Lymphoproliferative Disorders / drug therapy*
  • Lymphoproliferative Disorders / immunology
  • Middle Aged
  • Rituximab
  • Thrombocytopenia / drug therapy*
  • Young Adult


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Murine-Derived
  • Immunosuppressive Agents
  • Rituximab