Chronic Gvhd

The treatment of chronic GVHD has also been problematic with long-term immunosuppressive therapy required for many patients with symptomatic disease. With the routine use of PBPC, and the transplantation of older patients, the problem of extensive chronic GVHD has increased.9798 Treatment strategies must weigh the need to ameliorate the clinical manifestations of chronic GVHD against the risks of long-term (often lifetime) administration of immunosuppressive medications (including but not limited to infection, osteonecrosis, and secondary malignancy). Some recent series have focused on local control of chronic GVHD manifestations, such as oral cyclosporine rinses or ophthalmic cyclosporine solution for xerostomia and xerophthalmia, respectively.99100 Extracorporeal photopheresis has been shown to be an effective salvage strategy for patients with steroid refractory GVHD.101 The cumulative morbidity of immuno-suppressive therapy can hopefully be lessened with this approach. Long-term venous access issues can be problematic given the heightened infection risk of patients with chronic GVHD.

The optimal therapy for extensive chronic GVHD remains uncertain. An alternate-day corticosteroid and cyclosporine regimen has been shown to be effective in the management of chronic GVHD with an acceptable toxicity profile.102 Corticosteroids as a single agent have been shown to be superior to combined corticos-teroids and azathioprine for chronic GVHD.103 For their steroid sparing effect, however, combination regimens are often employed in the treatment of chronic GVHD. Newer agents with substantial activity in chronic GVHD include MMF104 and sirolimus105 (Table 98.4). Thalidomide has demonstrated some activity in steroid refractory chronic GVHD.106 Clofazimine has been shown to have efficacy in the treatment of the connective tissue variant of chronic GVHD.107 Ursodiol may ameliorate the clinical manifestations of hepatic GVHD.108 Other vitally important supportive care aspects of the management of chronic GVHD include immunoglobulin repletion for patients with severe hypogammaglobulinemia, antimicrobial prophylaxis (e.g., penicillin for Streptococcus pneumoniae, co-tri-moxazole for pneumocystis carinii pneumonia (PCP) prophylaxis), physical therapy to prevent joint contractures, and frequent dental and ophthalmological evaluations to address dental hygiene and to evaluate for and treat corneal ulceration, and ocular infections, respectively.

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