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: 4.96). 06/2005; 129(4):534-8. DOI: 10.1111/j.1365-2141.2005.05496.x
Source: PubMed

ABSTRACT 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.

  • Blood 03/2014; 123(13):1978. DOI:10.1182/blood-2014-01-549477 · 9.78 Impact Factor
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    ABSTRACT: The clinical outcome, response to treatment, and occurrence of acute complications, were retrospectively investigated in 308 primary autoimmune hemolytic anemia (AIHA) cases and were correlated with serological characteristics and severity of anemia at onset. Patients had been followed-up for a median of 33 months (range 12-372); 60% were warm AIHA, 27% cold hemagglutinin disease, 8% mixed, and 5% atypical (mostly DAT-negative). The latter two categories showed more frequently a severe onset (Hb levels ≤6 g/dL) along with reticulocytopenia. The majority of warm AIHA received first line steroid therapy only, whereas patients with mixed and atypical forms were more frequently treated with 2 or more therapy lines, including splenectomy, immunosuppressants and rituximab. The cumulative incidence of relapse was increased in more severe cases (HR 3.08, 95% CI 1.44-6.57 for Hb ≤6 g/dL, p<0.001). Thrombotic events were associated to Hb levels ≤6 g/dL at onset, intravascular hemolysis and previous splenectomy. Predictors of a fatal outcome were severe infections particularly in splenectomized cases, acute renal failure, Evans' syndrome and multi-treatment (4 or more lines). The identification of severe and potentially fatal AIHA in a largely heterogeneous disease requires particular experienced attention by clinicians.
    Blood 09/2014; 124(19). DOI:10.1182/blood-2014-06-583021 · 9.78 Impact Factor
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    ABSTRACT: Autoimmune hemolytic anemia (AIHA) is a relatively uncommon disorder caused by autoantibodies directed against self red blood cells. It can be idiopathic or secondary, and classified as warm, cold (cold hemagglutinin disease (CAD) and paroxysmal cold hemoglobinuria) or mixed, according to the thermal range of the autoantibody. AIHA may develop gradually, or have a fulminant onset with life-threatening anemia. The treatment of AIHA is still not evidence-based. The first-line therapy for warm AIHA are corticosteroids, which are effective in 70-85% of patients and should be slowly tapered over a time period of 6-12 months. For refractory/relapsed cases, the current sequence of second-line therapy is splenectomy (effective approx. in 2 out of 3 cases but with a presumed cure rate of up to 20%), rituximab (effective in approx. 80-90% of cases), and thereafter any of the immunosuppressive drugs (azathioprine, cyclophosphamide, cyclosporin, mycophenolate mofetil). Additional therapies are intravenous immunoglobulins, danazol, plasma-exchange, and alemtuzumab and high-dose cyclophosphamide as last resort option. As the experience with rituximab evolves, it is likely that this drug will be located at an earlier point in therapy of warm AIHA, before more toxic immunosuppressants, and in place of splenectomy in some cases. In CAD, rituximab is now recommended as first-line treatment.
    Haematologica 10/2014; 99(10):1547-1554. DOI:10.3324/haematol.2014.114561 · 5.87 Impact Factor


Available from
May 16, 2014