Correspondence

High-Dose Pulsed Dexamethasone for Immune Thrombocytopenia

N Engl J Med 1997; 337:425-427August 7, 1997

Article

To the Editor:

An important and unresolved problem is the treatment of patients with idiopathic thrombocytopenic purpura in whom severe thrombocytopenia persists despite splenectomy. In the June 2, 1994, issue, Andersen reported excellent results in 10 patients with refractory idiopathic thrombocytopenic purpura (5 men and 5 women) who were treated with high-dose dexamethasone.1 In all the patients who completed six cycles of dexamethasone therapy (40 mg daily for 4 consecutive days every 28 days), platelet counts not only increased but remained above 100×10⁹ per liter for at least 6 months after the last cycle of treatment.

We treated 10 consecutive patients with refractory idiopathic thrombocytopenic purpura (Table 1Table 1Characteristics of the Patients and Platelet Counts before and after the Completion of Pulsed High-Dose Dexamethasone Therapy and at the End of Follow-up.). All 10 patients had undergone splenectomy and had had relapses after several different treatments. The mean (±SD) age of our patients was similar to the mean age of the patients described by Andersen (36±13 and 41±12 years, respectively; P>0.05), and the mean duration of disease was also similar (43±14 months and 46±22 months, respectively; P>0.05).1 All 10 patients underwent six cycles of the high-dose dexamethasone protocol. The patients were followed for 10 to 22 months after the completion of the trial. As Table 1 shows, none of our patients had a significant increase in the platelet count.

Caulier et al. used a similar protocol,2 and none of their patients had a stable increase in the platelet count to a level higher than 100×10⁹ per liter. We do not think that high-dose dexamethasone is effective in the treatment of refractory idiopathic thrombocytopenic purpura. Controlled multicenter trials may help identify new therapeutic options for this disease.

Halûk Demiroğlu, M.D.
Semra Dündar, M.D.
Hacettepe University Medical School, Ankara, 06100, Turkey

2 References

1. 1

   Andersen JC. Response of resistant idiopathic thrombocytopenic purpura to pulsed high-dose dexamethasone therapy. N Engl J Med 1994;330:1560-1564[Erratum, N Engl J Med 1994;331:283.]
   Full Text | Web of Science | Medline

2. 2

   Caulier MT, Rose C, Roussel MT, Huart C, Bauters F, Fenaux P. Pulsed high-dose dexamethasone in refractory chronic idiopathic thrombocytopenic purpura: a report on 10 cases. Br J Haematol 1995;91:477-479
   CrossRef | Web of Science | Medline

Author/Editor Response

Dr. Andersen replies:

To the Editor: More than four years after the completion of treatment, 7 of 10 consecutive outpatients with resistant idiopathic thrombocytopenic purpura who were treated with pulsed high-dose dexamethasone1 remain in complete clinical remission; 2 are in partial remission. One patient has had a hematologic relapse but remains asymptomatic. Table 1Table 1Rates of Response to Pulsed High-Dose Dexamethasone. summarizes these results, as well as those for 25 additional patients with new-onset, resistant, or lupus-associated idiopathic thrombocytopenic purpura treated at Wayne State University.

Although optimal dosing schedules have not been established, it appears likely that a division of the daily dose, shortened treatment cycles, and the absence of a meaningful rise in the platelet count after three cycles of pulsed dexamethasone therapy presage a poor response. Regional or population-based variability in the response rate may reflect, in part, genetically conditioned variability in dexamethasone clearance2,3 (and Santen RJ: personal communication). Patients with a relapse after an initial remission with pulsed dexamethasone often have a response to one or two retreatment cycles.

Not knowing the actual characteristics of the patients studied by Demiro Şglu and Dündar, I cannot determine which, if any, of the above factors may explain the dramatic difference in the response rate. A natural tendency to use a newly reported regimen to achieve a benefit in patients with the poorest responses may provide a partial explanation, as may population-based differences in drug metabolism and availability.

Only randomized, prospective clinical trials in well-characterized patient populations can determine the value of a treatment for idiopathic thrombocytopenic purpura. A national multicenter group for the study of idiopathic thrombocytopenic purpura has been formed to examine critically, in patients with several different categories of immune thrombocytopenia, response rates to both conventional and newer therapies. The initial comparison will be between conventional prednisone therapy and pulsed-dexamethasone therapy in obviating the need for splenectomy in patients with newly diagnosed idiopathic thrombocytopenic purpura.

Judith C. Andersen, M.D.
Harper Hospital, Detroit, MI 48201

3 References

1. 1

   Andersen JC. Response of resistant idiopathic thrombocytopenic purpura to pulsed high-dose dexamethasone therapy. N Engl J Med 1994;330:1560-1564[Erratum, N Engl J Med 1994;331:283.]
   Full Text | Web of Science | Medline

2. 2

   Santen R, Lipton A. Successful medical adrenalectomy -- the role of altered drug metabolism. Clin Res 1973;21:653-653 abstract.
   

3. 3

   Lipton A, Santen RJ. Medical adrenalectomy using aminoglutethimide and dexamethasone in advanced breast cancer. Cancer 1974;33:503-512
   CrossRef | Web of Science | Medline

Citing Articles (12)

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   Jin Ah Yoon, Chan Kyu Kim, Se Hyung Kim, Kyung Ha Kim, Hyun Jung Kim, Sung Kyu Park, Sang Chul Lee, Nam Su Lee, Sang Byung Bae, Kyu Taek Lee, Jong Ho Won, Hee Sook Park, Dae Sik Hong. (2009) Initial Therapy with High-Dose Dexamethasone for Patients with Idiopathic Thrombocytopenic Purpura. The Korean Journal of Hematology 44:1, 22
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   Ara Metjian, Charles S Abrams. (2008) New insights and therapeutics for immune-mediated thrombocytopenia. Expert Review of Cardiovascular Therapy 6:1, 71-84
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   Bertrand Godeau, Drew Provan, James Bussel. (2007) Immune thrombocytopenic purpura in adults. Current Opinion in Hematology 14:5, 535-556
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   Taro Horino, Atsushi Sasaoka, Toshihiro Takao, Takafumi Taguchi, Hiroshi Maruyama, Hiroyuki Ito, Shigeki Takemoto, Hirokuni Taguchi, Kozo Hashimoto. (2005) Immune thrombocytopenic purpura associated with rheumatoid arthritis: case report. Clinical Rheumatology 24:6, 641-644
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   F. Borst, J. J. Keuning, H. Hulsteijn, H. Sinnige, G. Vreugdenhil. (2004) High-dose dexamethasone as a first- and second-line treatment of idiopathic thrombocytopenic purpura in adults. Annals of Hematology 83:12, 764-768
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   R. Stasi, D. Provan. (2004) Management of Immune Thrombocytopenic Purpura in Adults. Mayo Clinic Proceedings 79:4, 504-522
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   Cheng, Yunfeng, Wong, Raymond S.M., Soo, Yannie O.Y., Chui, Chung Hin, Lau, Fung Yi, Chan, Natalie P.H., Wong, Wai Shan, Cheng, Gregory, . (2003) Initial Treatment of Immune Thrombocytopenic Purpura with High-Dose Dexamethasone. New England Journal of Medicine 349:9, 831-836
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   Emmanuelle Bourgeois, Marie T. Caulier, Catherine Delarozee, Marc Brouillard, Francis Bauters, Pierre Fenaux. (2003) Long-term follow-up of chronic autoimmune thrombocytopenic purpura refractory to splenectomy: a prospective analysis. British Journal of Haematology 120:6, 1079-1088
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   (2003) Guidelines for the investigation and management of idiopathic thrombocytopenic purpura in adults, children and in pregnancy. British Journal of Haematology 120:4, 574-596
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10. 10

    G GUTIERREZESPINDOLA. (2003) High Doses of Dexamethasone in Adult Patients with Idiopathic Thrombocytopenic Purpura. Archives of Medical Research 34:1, 31-34
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11. 11

    Roberto Stasi, Maurizio Brunetti, Adalberto Pagano, Elisa Stipa, Mario Masi, Sergio Amadori. (2000) Pulsed Intravenous High-Dose Dexamethasone in Adults with Chronic Idiopathic Thrombocytopenic Purpura. Blood Cells, Molecules, and Diseases 26:6, 582-586
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12. 12

    James N George, Kiarash Kojouri, Jedidiah J Perdue, Sara K Vesely. (2000) Management of patients with chronic, refractory idiopathic thrombocytopenic purpura. Seminars in Hematology 37:3, 290-298
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