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• W2064276088 abstract "Most children with immune thrombocytopenic purpura (ITP) have a limited illness with minimal complications. However, a small percentage of affected patients develop chronic disease or have troublesome bleeding. For these particularly challenging children multiple treatment modalities are available, but no randomized controlled trials have ever been designed to compare them. Children with severe or chronic ITP require treatment in several settings: (1) emergent therapy for severe bleeding symptoms, (2) maintenance therapy to increase the platelet count to a more “tolerable” level (i.e., allowing for normal activities) while awaiting spontaneous remission, and (3) induction of permanent remission. Traditional treatments, such as corticosteroids, intravenous immunoglobulin (IVIG), and anti-D immunoglobulin, can be useful for acute bleeding episodes 1. In some children it is possible to continue intermittent therapy with these agents for bleeding or severe thrombocytopenia; however, patients may cease to have a response or tire of waxing and waning platelet counts and may therefore benefit from medications that induce a more stable long-term effect. Chronic low dose steroid treatment, a mainstay of therapy in adult ITP, has been employed in children as well. Its therapeutic effects however, remain unclear and unstudied. Long-term use of corticosteroids, even in modest doses, is associated with many undesirable side effects such as weight gain, moodiness, osteoporosis, hypertension, and hyperglycemia. In order to avoid the highly toxic effects of steroids, other medications have been used to induce long-term remission and wean patients from their steroid medication. These include vincristine, danazol, cyclosporine, and cyclophosphamide 2, 3. Rituximab and new thrombopoeitin-like drugs have also recently gained attention 4-6 in this clinical setting. Rituximab, a monoclonal anti-CD20 antibody, has some efficacy 4, however it is costly, can only be administered intravenously, and ideal dosing for pediatric ITP is unknown. There is currently much “hype” surrounding the new thrombopoeitin-like agents. However, they can only temporarily increase the platelet count and not provide “curative” therapy. Sobota et al. now offer in the current issue of Pediatric Blood & Cancer a new look at another agent for the treatment of patients with chronic refractory ITP. In their retrospective case series, they report on the use of 6-Mercaptopurine (6-MP). 6-MP, a purine antimetabolite, has been in existence for over half a century as therapy for acute lymphoblastic leukemia. Other purine antimetabolites such as azathioprine and more recently mycophenolate mofetil have been employed for chronic ITP in adults. Azathioprine was shown to have response rates of 64–85% and two small studies of mycophenolate mofetil describe response rates of 57% and 71% 3. Yet, little has been published on the use in ITP of 6-MP, the first purine analog employed in clinical practice. Table I compares these three medications. There is really very little difference between them with regard to mechanism of action and side effect profiles, yet an appreciable difference in cost between the older purine antimetabolites and mycophenolate mofetil. No published data directly compare their clinical effectiveness. Often times older more traditional therapies, such as 6-MP, are abandoned in favor of newer and seemingly more exciting agents. Sobota et al. are thus to be commended for revisiting a traditional medication and applying it in a new treatment setting. In a condition such as chronic childhood ITP that often has few clinical manifestations, the treatment should not be worse than the disease itself. In the report of Sobota and coworkers only 14% of patients experienced a side effect, the most common of which was mild alteration in liver function. Other agents historically used to treat refractory ITP may have more troublesome adverse effects such as hemorrhagic cystitis (cyclophosphamide), hirsutism (cyclosporine), and allergic reactions (rituximab). The long-term durability of responses to agents used in refractory ITP is important. In the current series of 29 patients there was an 83% response rate, yet only four children (two with ITP) remained in remission without additional immunosuppressive medications following discontinuation of 6-MP.Approximately 40% of children with chronic ITP eventually achieve remission 7, and it is thus not possible to determine if 6-MP truly “cured” ITP in these patients. Traditionally, splenectomy has been considered the only treatment that induces life-long remission in ITP. Approximately 75% of affected children can be expected to have a lasting response to splenectomy 8. Concerns arise, however, over the long-term risk for sepsis and that many children may remit over time without the procedure 9. For these reasons, long-term therapy with agents such as 6-MP may be preferable in children who are younger, earlier in the natural history of their disease, or who wish to avoid a surgical procedure. The ideal treatment of refractory chronic ITP during childhood remains unclear. Prospective studies are difficult to conduct given the relative rarity of severe chronic ITP, its multiple treatment approaches, and the spontaneous remissions that may occur even without medical therapy. Retrospective case series, such as the one described by Sobota et al., therefore provide invaluable insights that may limit the use of steroids, temporarily support patients destined to eventually have a spontaneous remission, avoid splenectomy, and possibly even “cure” the disease." @default.
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• W2064276088 title "6-mercaptopurine: Teaching an old drug new tricks" @default.
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• W2064276088 doi "https://doi.org/10.1002/pbc.21785" @default.
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