Childhood immune thrombocytopenia (ITP) has a favorable outcome in most cases but severe bleeding may occur, mostly in children with very low platelet counts. Although first-line therapies are well defined, management of refractory ITP is not consensual. Vinblastine (VBL) is one second-line treatment in adult series. We reported all childhood refractory ITP treated with VBL in our unit in past 10 years. VBL was administered by four weekly injections (6 mg/m 2 / dose) in initial phase, followed by maintenance phase according to response and tolerance. Seventeen patients with refractory ITP, significant clinical bleeding (Buchanan bleeding score 5 3), and plateletcount <20 3 10 9 /L were treated with VBL. In the initial phase, response rate was 11/17. In these 11 patients, response rate in maintenance was 8/11 (in combination therapies in three cases) with a median duration of VBL treatment of 13 months (2-83); 1/11 had a loss of response and 2/11 stopped treatment because of side effect. Eleven patients had side effects, mainly neuropathic pain, completely reversible after dose reduction or treatment interruption. We conclude that VBL could be considered in the treatment schedule of childhood ITP: it could rapidly increase platelet count and sustain response, if necessary in combination therapies.
ITP is an autoimmune disorder of adults and children [1]. Pathogenesis is multifactorial with increased platelet destruction and impaired thrombopoiesis [2].
Incidence of childhood ITP is 4.0-5.5 per 100,000 per year [3,4]. In most cases it resolves spontaneously within 6 months. But 15-25% of children with primary ITP develop a chronic form [3,4]. An international working group recently described three phases of the disease: newly diagnosed ITP, within 3 months from diagnosis; persistent ITP, between 3 and 12 months from diagnosis; and chronic ITP, for more than 12 months [1]. In persistent and chronic ITP, many children have a platelet count of more than 20 3 10 9 / L. They are not symptomatic and need specific therapy only in case of surgery, dental extraction, or injury [5]. But when platelet count is less than 20 3 10 9 /L, severe bleeding, in particular intracranial hemorrhage (ICH), may occur [6].
First-line therapies in childhood ITP are polyclonal intravenous immunoglobulin and corticosteroids [5,7] but in case of no response or loss of response following these therapies, choice of treatment is not consensual [1].
In second-line therapies, medical treatments as rituximab, danazol, colchicine, azathioprine, or cyclosporine have been tried with variable efficiency [7,8] but surgical treatment by splenectomy has still the best results with complete remission in 70% of patients [9], which is counter-balanced by side effects like infectious and thrombotic complications [10,11].
As far as some results have been reported with vinca alkaloids (e.g., vincristine and VBL) in adult [12,13] and childhood [14,15] refractory ITP, we decided in 2001 to use VBL in our Pediatric Department of Hematology as a modality of standard care in second-line therapies of symptomatic persistent childhood ITP. Ten years later, while new therapies are available in ITP, we would like to report a monocentric retrospective analysis of VBL results in the treatment of children and adolescents with refractory primary ITP.
Detailed results are presented in Table SI (Supporting Information). Seventeen patients with refractory ITP, ten males and seven females, median age at diagnosis 8 years (range 1-16), were treated by VBL in our department. Three children had no typical primary ITP: one of them (patient 4) suffered from Evans syndrome with autoimmune hemolytic anemia diagnosed and treated without recurrence at the age of five, 1 year before thrombocytopenia appeared; two other children (patients 9 and 11) had autoimmune neutropenia diagnosed in the same time period as ITP.