A trial of high-dose dexamethasone therapy for chronic idiopathic thrombocytopenic purpura in childhood

doi:10.1016/S0022-3476(97)70304-4

The Journal of Pediatrics

Volume 130, Issue 1, January 1997, Pages 13-16

https://doi.org/10.1016/S0022-3476(97)70304-4 Get rights and content

Abstract

Objective: To determine the efficacy of high-dose dexamethasone in chronic idiopathic thrombocytopenic purpura of childhood.

Methods: Seventeen patients entered the protocol. Dexamethasone was to be given orally in two divided doses at a dosage of 20 mg/m ² for 4 consecutive days every 28 days for six courses.

Results: One month after the end of the sixth course, six patients (35%) had platelet values within the normal range. One year later, five patients (29%) still have normal platelet values. Five patients discontinued treatment before completion because of lack of response and in one case for important side effects. Duration of the disease before treatment was inversely correlated with response to dexamethasone: 5 of 10 patients who had had thrombocytopenia for 30 months or less went into remission, as opposed to none of the seven who had been sick for a longer period ( p = 0.04). Side effects included fatigue or irritability, anxiety, abdominal pain, striae, hirsutism, acne, and weight gain.

Conclusions: Contrary to what is observed in adults, in our patients pulsed dexamethasone therapy did not prove to be uniformly effective. However, in view of its effectiveness in a third of the patients, acceptable side effects, and low cost, we believe that this treatment could be considered in patients with chronic idiopathic thrombocytopenic purpura who do not tolerate the disease well, especially if no more than 3 years have elapsed since diagnosis. Larger studies will be necessary to define which patients will respond to this type of therapy.

Section snippets

METHODS

Seventeen patients (10 girls, 7 boys) aged between 4 and 17 years (median, 10 years) who had ITP of 6 months' to 14 years' duration were enrolled in this study. These represented the entire population of patients with symptomatic chronic ITP followed at our institutions, for whom no contraindication to the use of dexamethasone existed. Diagnosis had been made on clinical grounds, in accordance with established criteria. In all cases a bone marrow aspirate had shown normal to increased numbers

RESULTS

One month after the end of therapy, six patients (35% of the total) had platelet counts within the normal range. In six children the platelet count increased at the end of each of the six courses but rapidly returned to the pretreatment values. One patient discontinued therapy after the fourth course and four after the fifth because of lack of response, associated in one case with severe side effects. One year after the end of therapy, five of the six responders (29% of the total) still had

DISCUSSION

Complete success was recently reported in treating 10 adults affected by chronic ITP with brief, repeated courses of dexamethasone therapy, given under the assumption that this drug at the high dosage employed is capable of suppressing or even eradicating the population of plasma cells responsible for the continued production of anti-platelet antibody and hence of curing chronic ITP. ⁴ These encouraging results prompted us to start a trial of the same treatment in pediatric patients. We chose

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Treatment of chronic childhood immune thrombocytopenic purpura with intramuscular anti-D immunoglobulin
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Protocol for the study and treatment of primary immune thrombocytopenia: PTI-2018
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La trombocitopenia inmune primaria, anteriormente conocida como púrpura trombocitopénica inmune, es una enfermedad cuyo manejo diagnóstico y terapéutico ha sido siempre controvertido. La Sociedad Española de Hematología y Oncología Pediátricas, a través del grupo de trabajo de la PTI, ha actualizado el documento con las recomendaciones protocolizadas para el diagnóstico y tratamiento de esta enfermedad, basándose en las guías clínicas disponibles actualmente, revisiones bibliográficas, ensayos clínicos y el consenso de sus miembros. El objetivo principal es disminuir la variabilidad clínica en los procedimientos diagnósticos y terapéuticos con el fin de obtener los mejores resultados clínicos, los mínimos efectos adversos y preservar la calidad de vida.
Primary immune thrombocytopenia, formerly known as immune thrombocytopenic purpura, is a disease for which the clinical and therapeutic management has always been controversial. The ITP working group of the Spanish Society of Paediatric Haematology and Oncology has updated its guidelines for diagnosis and treatment of primary immune thrombocytopenia in children, based on current guidelines, bibliographic review, clinical assays, and member consensus. The main objective is to reduce clinical variability in diagnostic and therapeutic procedures, in order to obtain best clinical results with minimal adverse events and good quality of life.
The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia
2011, Blood
Citation Excerpt :
In a prospective, randomized trial of 6 cycles of high-dose dexamethasone (0.6 mg/kg/d for 4 days every 4 weeks) and IVIg (800 mg/kg with a second dose if platelet count is less than 30 × 109/L at 48 hours for 6 cycles), complete or partial remissions occurred in 25% (5/20) of patients initially treated with corticosteroids or crossed over to this therapy after failure to respond to IVIg.43 Small prospective observational studies yield similar results with frequent adverse events.44-47 The 1996 ASH guideline noted that numerous agents such as azathioprine, danazol, and interferon have been used in a small number of children and adolescents with chronic or persistent ITP who failed to respond to more conventional therapy.
Immune thrombocytopenia (ITP) is commonly encountered in clinical practice. In 1996 the American Society of Hematology published a landmark guidance paper designed to assist clinicians in the management of this disorder. Since 1996 there have been numerous advances in the management of both adult and pediatric ITP. These changes mandated an update in the guidelines. This guideline uses a rigorous, evidence-based approach to the location, interpretation, and presentation of the available evidence. We have endeavored to identify, abstract, and present all available methodologically rigorous data informing the treatment of ITP. We provide evidence-based treatment recommendations using the GRADE system in those areas in which such evidence exists. We do not provide evidence in those areas in which evidence is lacking, or is of lower quality—interested readers are referred to a number of recent, consensus-based recommendations for expert opinion in these clinical areas. Our review identified the need for additional studies in many key areas of the therapy of ITP such as comparative studies of “front-line” therapy for ITP, the management of serious bleeding in patients with ITP, and studies that will provide guidance about which therapy should be used as salvage therapy for patients after failure of a first-line intervention.
International consensus report on the investigation and management of primary immune thrombocytopenia
2010, Blood
Citation Excerpt :
However, side effects such as sleeplessness, aggressive behavior, and loss of concentration are unacceptably high.198 HDMP (given as an oral 7-day course of 30 mg/kg/d for 3 days followed by 20 mg/kg/d for 4 days) has been used as an alternative to IVIg200-202 (evidence level Ib-III). See “First-line/initial treatment options to raise platelet counts in children.”
Previously published guidelines for the diagnosis and management of primary immune thrombocytopenia (ITP) require updating largely due to the introduction of new classes of therapeutic agents, and a greater understanding of the disease pathophysiology. However, treatment-related decisions still remain principally dependent on clinical expertise or patient preference rather than high-quality clinical trial evidence. This consensus document aims to report on new data and provide consensus-based recommendations relating to diagnosis and treatment of ITP in adults, in children, and during pregnancy. The inclusion of summary tables within this document, supported by information tables in the online appendices, is intended to aid in clinical decision making.
The cumulative burden of oral corticosteroid side effects and the economic implications of steroid use
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Oral corticosteroids (OCS) are a key part of therapy regimens for a diverse variety of conditions. Despite their efficacy, they are associated with a wide variety of adverse events. The purpose of this review was to identify the range of adverse events that have been reported to be related to oral corticosteroids, examine the factors that influence their incidence and estimate the economic burden caused by these adverse events. In 61 identified studies, 21 different categories of OCS related adverse events were reported with increased fracture risk being the category most frequently described. Most studies that examined factors linked to the incidence of OCS related adverse events found that dose, age, gender, duration of use, treatment history, smoking habits or cholesterol level were influential in determining risk. Additionally, a cumulative economic analysis of selected adverse events found the annual cost of treating these events in the UK to be at least £165 per patient taking OCS. The clinical and economic burden of OCS related adverse events highlights the need for OCS sparing therapies to be developed.
Current Options for the Treatment of Idiopathic Thrombocytopenic Purpura
2007, Seminars in Hematology
Citation Excerpt :
In another study, none of the nine patients with chronic ITP responded to high-dose dexamethasone, and five could not tolerate the treatment.41 In children with chronic ITP, few long-lasting remissions have been reported following high-dose dexamethasone42 but in one study, three of seven children achieved a platelet count above 50 × 109/L after 6 months, including one for whom the response was maintained to 1 year.43 In conclusion, corticosteroids remain the cornerstone of treatment for patients with newly diagnosed ITP and should be tried in chronic patients who require treatment.
Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disease characterized by low platelets and bleeding. Platelet autoantibodies result in accelerated platelet destruction by the reticuloendothelial cells in the spleen and liver, overwhelming the compensatory capability of the bone marrow to increase platelet production. The goal of treatment for patients with ITP is to raise the platelet count to high enough levels to prevent bleeding using the least toxic therapy, recognizing the generally benign nature of the illness. Corticosteroids, intravenous immune globulin, and splenectomy remain mainstays of treatment; however, newer therapies including rituximab and the thrombopoietin receptor agonists are remodeling conventional treatment algorithms. Immune suppressant medications and cytotoxic drugs continue to be used in patients with severe and chronic refractory ITP with some success; however, estimates of the effect of these and other treatments are limited by the lack of randomized trials using clinical end points. In this article, treatments for ITP are reviewed with a focus on their mechanism of action and the best available evidence from clinical studies. A move towards early aggressive therapy may alter the natural history of this self-perpetuating illness.
High-dose dexamethasone as a replacement for traditional prednisone as the first-line treatment in children with previously untreated primary immune thrombocytopenia: a prospective, randomized single-center study
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^☆: Supported by the Ministero dell' Universitá e della Ricerca Scientifica e Technologica (60% 1995; Dr. Borgna-Pignatti) and by the Associazione Italiana per la Ricerca sul Cancro (Dr. Locatelli).

^☆☆: Reprint requests: Caterina Borgna-Pignatti, Istituto di Pediatria Universitá di Ferrara, Via Savonarola 9, 44100 Ferrara, Italy.

^★: 0022-3476/97/$5.00 + 0 9/21/77543

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A trial of high-dose dexamethasone therapy for chronic idiopathic thrombocytopenic purpura in childhood☆,☆☆,★

Abstract

Section snippets

METHODS

RESULTS

DISCUSSION

Idiopathic thrombocytopenia, initial illness and long-term follow-up

Arch Dis Child

Intracranial hemorrhage in idiopathic thrombocytopenic purpura

Arch Dis Child

Treatment of chronic childhood immune thrombocytopenic purpura with intramuscular anti-D immunoglobulin

Br J Haematol