Graft-versus-host disease chronic

Filipovich AH, Weisdorf D, Pavletic S, et al. National Institutes of Health Consensus Development Project on criteria for clinical trials in chronic graft-versus-host disease I. Diagnosis and staging working group report. Biol Blood Marrow Transplant 2005 11 945-956. 

Chronic graft-versus-host disease Horwitz, M.E., Sullivan, K.M. (2006). Blood Rev, 20 (1) 15-27... 

Pentostatin for the treatment of chronic graft-versus-host disease in children Goldberg, J.D., Jacobsohn, D.A., Margolis, J., Chen, A.R., Anders, V., Phelps, M., Vogelsang, G.B. (2003). JPediatr Hematol Oncol, 25 (7) 584-588. 

Oral pilocarpine is moderately effective for treating xerostomia following irradiation of head and neck cancer. It may also be beneficial in relieving refractory xerostomia associated with chronic graft-versus-host disease (see Chapter 14). 

Durie, F. H., Aruffo, A., Ledbetter, J. A. el al. (1994). Antibody to the ligand of CD40, gp39, blocks the occurrence of the acute and chronic forms of graft-versus-host disease. J. Clin. Invest. 94, 1333-1338. 

Other potential uses for iron chelators are reducing post-ischaemic perfusion injury [23], organ transplantation [24] and graft versus host disease [25], as anticancer agents through their effect on cell proliferation [26], mobilizing iron from the reticuloendothelial cells in the anaemia of chronic disease [27], and selective metalloenzyme inhibitors of lipoxygenase and ribonucleotide reductase. 

Uses. Ciclosporin is used to prevent and treat rejection of organ transplants (kidney, liver, heart-lung) and bone marrow transplants. It may be given orally or i.v. In the context of transplantation, administration continues indefinitely and must be carefully monitored, including measurement of plasma concentration and renal function. It is generally stopped after 6 months in patients who have received a bone marrow transplant unless there is ongoing chronic graft-versus-host disease. 

Of 65 patients who survived for at least 6 months after bone marrow transplantation, 31 had some degree of alopecia and 19 had extensive alopecia (32). The mean minimum busulfan concentration was 656 ng/ml in patients who developed alopecia, compared with 507 ng/ ml in those who did not. Patients with more extensive alopecia had higher busulfan concentrations. In multivariate analysis, alopecia was associated with busulfan concentrations higher than the median (OR = 3.43 95% Cl = 3.04, 3.88), allogeneic transplantation (OR = 2.56 Cl = 2.28, 2.88), and female sex (OR = 1.96 Cl = 1.73, 2.88). There was no association between alopecia and chronic graft-versus-host disease. 

The efficacy of daclizumab in acute and chronic glucocorticoid-refractory graft-versus-host disease has been studied in 16 patients, of whom nine responded (2). However 14 developed infectious complications during treatment, with a high incidence of cytomegalovirus reactivation there were three infection-related deaths. 

WiUenbacher W, Basara N, Blau IW, Fauser AA, Kiehl MG. Treatment of steroid refractory acute and chronic graft-versus-host disease with dachzumab. Br J Haematol 2001 112(3) 820-3. 

There are still uncertainties about the possible relation between interferon alfa and an increased incidence or severity of acute graft-versus-host disease after bone marrow transplantation. Late-onset, severe, atypical chronic graft-versus-host disease has been attributed to interferon alfa (383). 

A 44-year-old woman received interferon alfa 6 MU/ day for relapse of chronic myeloid leukemia 7 years after successful bone marrow transplantation. About 2 years later, interferon alfa was withdrawn because of diffuse erythematous skin lesions with discoid lupus erythematosus on skin biopsy and severe dysphagia with esophagitis and pseudomembranes at endoscopy. Fever, bilateral pulmonary infiltrates, and respiratory distress syndrome subsequently developed, and she required mechanical ventilation. An open lung biopsy showed features of chronic pulmonary graft-versus-host disease. All her symptoms completely resolved with ciclosporin and corticosteroids. An infectious cause was ruled out. 

In this case, the clinical presentation was compatible with typical chronic graft-versus-host disease. Whether interferon alfa induced or aggravated chronic graft-versus-host disease in this patient was an open question. 

Serrano J, Prieto E, Mazarbeitia F, Roman A, Llamas P, Tomas JF. Atypical chronic graft-versus-host disease following interferon therapy for chronic myeloid leukaemia relapsing after allogeneic BMT. Bone Marrow Transplant 2001 27(l) 85-7. 

A 49-year-old man with acute myeloid leukemia underwent allogeneic bone marrow transplantation from his brother. Pre-existing pulmonary aspergillosis was treated with intravenous amphotericin. ACT scan of the chest and abdomen 120 ml of the non-ionic dimer iodix-anol was performed and 6 hours after the injection he developed generalized erythema with a pruritic painful skin rash. Skin biopsies showed changes typical of chronic graft-versus-host disease. He received prednisolone 50 mg orally and the rash resolved within a few weeks. 

Based on this report and a review of previously published cases, concomitant hypertension and the use of high-dose methylprednisolone were discussed as precipitating factors of tacrolimus neurotoxicity. In two other patients aged 4 and 15 years who had prolonged leukoencephalopathy, the underlying chronic graft-versus-host disease was thought to be a risk factor (34). 

Neutropenia occurred in 14 of 80 patients treated with thalidomide for refractory chronic graft-versus-host disease (69). The median thahdomide dose at which neutropenia developed was 200 mg qds. Eiythrocyte and platelet counts were not affected. After withdrawal of thalidomide the neutropenia resolved within a month (except in three patients, who died with refractory graft-versus-host disease). Six patients were rechallenged with thalidomide and again became neutropenic. 

Claman, H.N., JafFee, B.D., Huff, J.C. and Clark. RA. (1985). Chronic graft-versus-host disease as a model for scleroderma. II. Mast cell depletion with deposition of immunoglobulins in the skin and fibrosis. Cell Immunol. 94, 73-84. 

Thalidomide was formerly used as a sedative/hyp-notic. It was approved in 1998 by the US Food and Drug Administration for use as an immunosuppressant in the treatment of erythema nodosum leprosum. It is also used in the treatment of graft-versus-host disease (Orphan drug status in the United States), macular degeneration, oral ulcers in AIDS patients, and reflex sympathetic dystrophy associated with chronic pain syndromes. 

Excessive production of IL-3 has been described in several pathological conditions, especially in monocytic or myeloid leukemias and mast cell disorders. However, IL-3 can be measured in blood only after severe immunological stimuli, such as graft-versus-host disease or parasitic infestations. IL-3 may also play an important role in chronic allergic diseases. ... 

Berman M, Rabin L, O Donnell J, Gratwohl A, Graw R, Deisseroth A, et al. The Ever in long-term survivors of marrow transplant—Chronic graft-versus-host disease. J Clin Gastroenterol 1980 2 53-63. 

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