Blood, 1 August 2001, Vol. 98, No. 3, pp. 892-892
CORRESPONDENCE
To the editor:
Treatment of extensive chronic sclerodermatous
graft-versus-host disease with high-dose immunosuppressive therapy and
CD34+ autologous stem cell rescue
Beyond many complications of allogeneic hematopoietic stem cell
(HSC) transplantation, chronic graft-versus-host disease
(cGVHD) still remains one of the most important causes of impaired
quality of life. Sclerodermatous cGVHD (SC-GVHD), one of the most
disabling forms, resembles systemic sclerosis clinically and
histopathologically, in a somewhat different initial location and
morphologic appearance of collagen fibers.1,2 The skin
sclerosis in SC-GHVD might be considered a form of cutaneous fibrosis
with features of excessive tissue repair related to an immunologic
reaction between lymphocytes of the graft and tissue host
cells.3
The updated treatment approaches in progressive cGVHD were recently
summarized by Gazie4 and Vogelsang5; agents
like cyclosporine (CsA), corticosteroids, antilymphocyte globulin, mycophenolate mofetil, extracorporeal photopheresis, and monoclonal antibodies are recommended at the expense of unavoidable morbidity and
mortality. Recent investigations have suggested that the pathogenesis of cGVHD is more similar clinically to an autoimmune disease than to
acute GVHD.6,7 Treatment of autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, and so forth by autologous stem cell rescue and high-dose immunotherapy is a rapidly growing and encouraging approach that led us to use this
strategy in a progressive SC-GVHD patient, who was a 29-year-old male,
Ph+ CML patient in first chronic
phase.8,9 Within 2 years of diagnosis, he underwent
transplantation from his HLA-identical female sibling donor. After a
successful engraftment, on day 1 after transplantation, the patient
developed ichthyosis superimposed upon an early stage of de novo cGVHD.
The patient was in complete chimeric status and in complete molecular
remission. Chronic GVHD progressed, with complaints of edema of the
skin on the extremities, xerophthalmia, xerostomia, and hepatic
involvement, and the skin biopsy confirmed SC-GVHD. Dysphagia and
dyspnea progressed despite administration of CsA, oral corticosteroids,
and mycophenolate mofetil, and his performance status deteriorated, but
without thrombocytopenia. After receiving a written consent, we
mobilized the stem cells with cyclophosphamide (CY) and granulocyte
colony-stimulating factor, an immunomagnetic positive selection was
performed on Isolex 300i (Nexell, Irvine, CA), and 4.53 ×
106/kg CD34+ cells were reinfused
after conditioning with CY (50 mg/kg/day intravenously for 4 days) and
antithymocyte globulin (30 mg/kg/day intravenously for 3 days). The
hematopoietic recovery was rapid, and no major transplantation-related
complications were encountered. The improvement in the patient and
resolution of cGVHD were monitored by joint flexibility index,
measurement of skin thickness (by ultrasonography), skin biopsies, and
quality of life. After a 15-month follow-up, the patient was still on
low-dose prednisone but showed marked improvement in joint-movement
indexes (50%-70% increase), skin thickness (20%-30% decrease), and
quality of life (30%-40% increase). The improvement was more
pronounced on the face and upper extremities than on the lower
extremities. High-dose immunotherapy (HDIT) did not result in
progression of his native disease or a change in complete donor
chimeric status. The observation of marked improvement in our patient
with life-threatening refractory SC-GVHD after HDIT with autologous
peripheral blood stem cell (PBSC) rescue led us to comment
about this approach in the light of the recently published review
concerning therapy for cGVHD.5 Although our patient showed
a considerable improvement with HDIT and autologous stem cell support,
the underlying mechanism needs to be elucidated. A possible indication
and optimal timing of HDIT and autologous transplantation in extensive
SC-GVHD should be further analyzed in the context of recent
therapeutic options such as extracorporeal photoimmunotherapy,
etretinate, thalidomide, and monoclonal antibodies against
inflammatory cytokines.
Mutlu Arat, Osman Ilhan, Ender Akça Iayan, Harika Çelebi, Haluk Koç, and Hamdi Akan
Correspondence: Hamdi Akan, Department of Hematology,
Faculty of Medicine, Ankara University, Sihhiye, Ankara 06100, Turkey
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