Use of mycophenolate mofetil for chronic, refractory immune cytopenias in children with autoimmune lymphoproliferative syndrome

Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases/NIH, 10 Center Drive, Bethesda, MD 20892, USA.
British Journal of Haematology (Impact Factor: 4.71). 06/2005; 129(4):534-8. DOI: 10.1111/j.1365-2141.2005.05496.x
Source: PubMed


Autoimmune lymphoproliferative syndrome (ALPS) is a disorder of apoptosis associated most often with heritable FAS mutations leading to lymphadenopathy, hypersplenism and chronic refractory autoimmune cytopenias. Mycophenolate mofetil (MMF) was used to treat cytopenias in 13 ALPS patients aged 9 months to 17 years from a cohort of 118 children (aged < 18 years) and 82 adults. Twelve responded for a median follow-up of 49 weeks (range 38-240 weeks), defined by maintenance of adequate blood counts and reduction in dosage or cessation of other immunosuppressive agents. This preliminary experience suggests that MMF may spare steroid usage in patients with ALPS-associated cytopenias.

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Available from: V Koneti Rao
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    • "Infection occurred in 6/19 patients after a median period of 70 weeks (Gomez-Almaguer et al., 2010). Other reports have documented an initial response rate of 78–92% for refractory autoimmune cytopenias treated with mycophenolate mofetil with no significant adverse events reported (Kotb et al., 2005; Rao et al., 2005). Thus, the approach to treating autoimmune cytopenias in CVID is not dissimilar to the treatment of immune competent patients (Wang and Cunningham-Rundles, 2005). "
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    ABSTRACT: Common variable immunodeficiency (CVID) is a humoral immunodeficiency whose primary diagnostic features include hypogammaglobulinemia involving two or more immunoglobulin isotypes and impaired functional antibody responses in the majority of patients. While increased susceptibility to respiratory and other infections is a common thread that binds a large cross-section of CVID patients, the presence of autoimmune complications in this immunologically and clinically heterogeneous disorder is recognized in up to two-thirds of patients. Among the autoimmune manifestations reported in CVID (20-50%; Chapel et al., 2008; Cunningham-Rundles, 2008), autoimmune cytopenias are by far the most common occurring variably in 4-20% (Michel et al., 2004; Chapel et al., 2008) of these patients who have some form of autoimmunity. Association of autoimmune cytopenias with granulomatous disease and splenomegaly has been reported. The spectrum of autoimmune cytopenias includes thrombocytopenia, anemia, and neutropenia. While it may seem paradoxical "prima facie" that autoimmunity is present in patients with primary immune deficiencies, in reality, it could be considered two sides of the same coin, each reflecting a different but inter-connected facet of immune dysregulation. The expansion of CD21 low B cells in CVID patients with autoimmune cytopenias and other autoimmune features has also been previously reported. It has been demonstrated that this unique subset of B cells is enriched for autoreactive germline antibodies. Further, a correlation has been observed between various B cell subsets, such as class-switched memory B cells and plasmablasts, and autoimmunity in CVID. This review attempts to explore the most recent concepts and highlights, along with treatment of autoimmune hematological manifestations of CVID.
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    • "For accurate diagnosis of ALPS, these tests should be performed by laboratories familiar with the test methods and in which local normal values are established [88]. The best frontline treatment of patients who have ALPS is with mycophenolate mofetil (MMF); in the largest series of ALPS reported to date of treatment with this immunosuppressive agent, a response rate of 92% was observed [89]. Splenectomy should be avoided in ALPS cases because of the high risk for overwhelming postsplenectomy sepsis. "
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    ABSTRACT: Immune thrombocytopenic purpura (ITP) is an autoimmune disorder characterized by a low circulating platelet count caused by destruction of antibody-sensitized platelets in the reticuloendothelial system. ITP can be classified as childhood versus adult, acute versus chronic, and primary versus secondary. Persistence of thrombocytopenia defines the chronic form of the disorder. Secondary causes of ITP include collagen vascular disorders, immune deficiencies, and some chronic infections. This review focuses on the diagnosis and management of children who have acute and chronic ITP. Emphasis is placed on areas of controversy and new therapies.
    Full-text · Article · Feb 2010 · Hematology/oncology clinics of North America
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    • "Moreover, the effects of rituximab are generally relatively transient; patients that do respond will probably relapse and with the potential risk of CVID, we recommend avoiding use of rituximab in ALPS patients. MMF was found to be effective in another series (Koneti Rao et al, 2005). While we have had less success overall with this drug, we have also seen good responses in a few children with ALPS treated with MMF (unpublished data). "
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    ABSTRACT: We hypothesized that sirolimus, an mTOR inhibitor, may be effective in patients with autoimmune lymphoproliferative syndrome (ALPS) and treated patients who were intolerant to or failed other therapies. Four patients were treated for autoimmune cytopenias; all had a rapid complete or near complete response. Two patients were treated for autoimmune arthritis and colitis, demonstrating marked improvement. Three patients had complete resolution of lymphadenopathy and splenomegaly and all patients had a reduction in double negative T cells, a population hallmark of the disease. Based on these significant responses, we recommend that sirolimus be considered as second-line therapy for patients with steroid-refractory disease.
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