Correspondence

Autologous Hematopoietic Stem-Cell Transplantation for Behçet's Disease with Pulmonary Involvement

N Engl J Med 2001; 344:69January 4, 2001

Article

To the Editor:

The prognosis for patients with Behçet's disease and pulmonary involvement is poor.1 Half the patients die within three years after the onset of hemoptysis.2 We describe the successful treatment of two patients with Behçet's disease and pulmonary bleeding with the use of high-dose chemotherapy and hematopoietic stem-cell transplantation. Both patients had disease that was refractory to conventional immunosuppressive therapy and had recurrence of disease activity after attempts to reduce the doses of oral cyclophosphamide and prednisone.

The first patient, a 32-year-old man, presented with recurrent aphthous ulcers, fever, polyarthritis, erythema nodosum, and an intracardiac thrombus. His disease was controlled with high doses of corticosteroids. Later, hemoptysis and arteriovenous shunts developed in the right lung. These complications were resistant to oral immunosuppressive therapy with cyclophosphamide and methotrexate and required continuous administration of high doses of corticosteroids. Given the poor prognosis associated with pulmonary bleeding, we decided to intensify immunosuppression in this patient with high-dose chemotherapy followed by autologous hematopoietic stem-cell transplantation. After the patient had received cyclophosphamide at a dose of 4 g per square meter of body-surface area, we collected stem cells, which were subsequently enriched ex vivo for CD34+ cells. After conditioning with melphalan at a dose of 200 mg per square meter, we transplanted the enriched stem cells.

The second patient, a 49-year-old man, had recurrent aphthous ulcers, fever, posterior uveitis, Coombs'-negative hemolytic anemia, central nervous system involvement, and hemoptysis. There was a partial remission while he was being treated with oral cyclophosphamide and prednisone, but he relapsed after dose reduction. He received the same treatment for mobilization of CD34+ cells as the first patient. At that time, partial remission of disease activity was achieved.

Both patients had a very good response to the conditioning regimen and stem-cell transplantation. The first patient had complete remission of all signs and symptoms. After 18 months of follow-up, he is still in complete remission, without the need for additional medication. In the second patient, a regimen of high-dose melphalan and stem-cell transplantation led to complete resolution of the pulmonary infiltration and most of the other symptoms, including the hemolysis. Ten months after transplantation, the dose of prednisone has been reduced to 2.5 mg per day. In both patients, the toxic effects of the treatment regimen were minimal (consisting of only mild gastrointestinal effects and no serious infections or bleeding).

Although the follow-up time is short, our experience suggests that myeloablative chemotherapy with melphalan, followed by autologous transplantation of T-cell–depleted hematopoietic stem cells, is safe for the treatment of patients with Behçet's disease who have a poor prognosis. Intensive immunosuppression may lead to remission in such patients, although the duration of the responses remains unknown.

Manfred Hensel, M.D.
University of Heidelberg, 69115 Heidelberg, Germany

Andreas Breitbart, M.D.
University of Ulm, 89081 Ulm, Germany

Anthony D. Ho, M.D., Ph.D.
University of Heidelberg, 69115 Heidelberg, Germany

2 References

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   Sakane T, Takeno M, Suzuki N, Inaba G. Behçet's disease. N Engl J Med 1999;341:1284-1291
   Full Text | Web of Science | Medline

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   Hamuryudan V, Yurdakul S, Moral F, et al. Pulmonary arterial aneurysms in Behcet's syndrome: a report of 24 cases. Br J Rheumatol 1994;33:48-51
   CrossRef | Medline

Citing Articles (6)

Citing Articles

1. 1

   Jakob Passweg, Alan Tyndall. (2007) Autologous Stem Cell Transplantation in Autoimmune Diseases. Seminars in Hematology 44:4, 278-285
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2. 2

   Atsushi Nonami, Katsuto Takenaka, Chinatsu Sumida, Kumiko Aizawa, Kenjiro Kamezaki, Toshihiro Miyamoto, Naoki Harada, Koji Nagafuji, Takanori Teshima, Mine Harada. (2007) Successful Treatment of Myelodysplastic Syndrome (MDS)-related intestinal Behçet's Disease by Up-front Cord Blood Transplantation. Internal Medicine 46:20, 1753-1756
   CrossRef

3. 3

   A. Tyndall, R. Saccardi. (2005) Haematopoietic stem cell transplantation in the treatment of severe autoimmune disease: results from phase I/II studies, prospective randomized trials and future directions. Clinical and Experimental Immunology 141:1, 1-9
   CrossRef

4. 4

   R. E. Hough, J. A. Snowden, N. M. Wulffraat. (2005) Haemopoietic stem cell transplantation in autoimmune diseases: a European perspective. British Journal of Haematology 128:4, 432-459
   CrossRef

5. 5

   Alan Tyndall, Thomas Daikeler. (2005) Autologous Hematopoietic Stem Cell Transplantation for Autoimmune Diseases. Acta Haematologica 114:4, 239-247
   CrossRef

6. 6

   A Gratwohl, J Passweg, I Gerber, A Tyndall. (2001) Stem cell transplantation for autoimmune diseases. Best Practice & Research Clinical Haematology 14:4, 755-776
   CrossRef