Pyrimethamine and Sulfadoxine for Treatment of Autoimmune Lymphoproliferative Syndrome

Launched by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES (NIAID) · Mar 28, 2001

Keywords

ClinConnect Summary

The Autoimmune Lymphoproliferative Syndrome is an inherited disease associated with a defect of lymphocyte apoptosis, lymphoproliferation and autoimmunity. Although, there are treatments for many of its autoimmune complications, there currently is no safe and effective therapy for this syndrome itself. Recently investigators in Europe serendipitously found that a child with ALPS type I had significant clinical improvement while on pyrimethamine/sulfadoxine (Fansidar) for Pneumocystis carinii prophylaxis.

Based on this finding, we propose to conduct a pilot study to obtain information on sa...

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ALL

Eligibility criteria

• • INCLUSION CRITERIA
• • All subjects must fulfill the current criteria for the diagnosis of ALPS (documented nonmalignant lymphadenopathy and/or splenomegaly of at least 1 year duration; greater than or equal to 1% TCR alpha/beta(+) CD4 (-) CD8(-) T cells in the peripheral blood and defective apoptosis by in vitro assay).
• • Subjects must be between 4 to 70 years of age.
• • Subjects must have a primary care physician.
• • EXCLUSION CRITERIA
• • Weigh less than 18 kgs (40 lbs.) will be excluded.
• • Have a known hypersensitivity reaction to pyrimethamine, sulfonamides, sulfonylureas, furosemide or other sulfa-like drugs will be excluded.
• • If you are receiving and requiring anti-folate drugs such as sulfonamides, trimethoprim, pyrimethamine and methotrexate will be excluded.
• • Patients who are G-6-PD deficient will be excluded.
• • Have a history of megaloblastic anemia, folate deficiency or a mean corpuscular volume greater than 101 CU MICR will be excluded.
• • Have a usual Hb concentration of less than 9 gm/dl, a platelet count of less than 75 K/mm(3), or an absolute neutrophil count of less than 1000/mm(3) will be excluded.
• • Liver disease determined by an ALT, AST or bilirubin 3 times above the upper limit of normal, and/or a serum albumin of less than 3 gm/dL will be excluded.
• • Renal dysfunction determined by a calculated creatinine clearance of less than or equal to 70 ml/min/1.73 m(2) in children and less than or equal to 60 ml/min in adults will be excluded.
• • Patients on immunosuppression (eg: corticosteroid, azathioprine, cyclophosphamide, etc.) are not eligible if the dose of the immunosuppressive drug has not been stable for at least 6 months prior to enrollment will be excluded.
• • Pregnant women will be excluded.
• • Women of reproductive age must have a negative pregnancy test and commit to use an acceptable method of contraception.
• • Unwilling or unable to comply with the need to have periodic blood tests to monitor possible side effects of treatment, or other major requirements of this study.