Giant cell myocarditis (GCM) is a rare and highly lethal disorder. The only multi-center case series with treatment data lacked data on cardiac function and had a retrospective design. We conducted a prospective, multi-center study of immunosuppression including cyclosporine and steroids for acute, microscopically-confirmed GCM. From June 1999 to June 2005, 11 subjects received high dose steroids, cyclosporine, and in 9 cases muromonab-CD3 in a standard protocol. Among these, 7 of 11 were female, the mean age was 60±15 years, and the mean time from symptom onset to presentation was 27±33 days. During one year of treatment, one subject died of respiratory complications at day 178, and 2 subjects received heart transplantations on days 2 and 27 respectively. Serial endomyocardial biopsies revealed that after 4 weeks of treatment the degree of necrosis, cellular inflammation and giant cells decreased (P=.001). One subject, who completed the trial, subsequently died of a fatal GCM recurrence after withdrawal of immunosuppression. Her case demonstrates for the first time that there is a risk of recurrent, sometimes fatal GCM after cessation of immunosuppression. In conclusion, this prospective study of immunosuppression for GCM confirms Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Posttransplant lymphoproliferative disorder (PTLD) is a frequently fatal complication of organ transplantation, occurring in 2% to 6% of cardiac recipients. Treatment remains poorly defined. Reduction in immunosuppression is effective in a proportion of cases, but mortality on the order of 80% is reported for patients requiring chemotherapy. The reason for such poor outcomes is unclear, but may be partly caused by the concomitant use of immunosuppressives. Nineteen consecutive cardiac recipients with PTLD were studied retrospectively in terms of clinical features and outcome. Patients were managed according to a uniform treatment approach. Initial therapy was a trial of reduced immunosuppression with concomitant acyclovir followed, if unsuccessful, by aggressive combination chemotherapy. The regimen used was predominantly ProMACE-CytaBOM. Six patients with phenotypically polyclonal PTLD presented less than 6 months after transplantation (median 6 weeks). Only 1 of 4 (25%) treated patients responded to reduced immunosuppression; the remainder died of multiorgan failure. Thirteen patients presented with phenotypically monoclonal disease > or = 6 months after transplantation. In 8 of 12 (75%) treated patients initial therapy was reduction in immunosuppression. None achieved complete remission (CR) and 2 experienced fatal rejection. Two patients achieved durable surgical CR. The remaining 8 patients received chemotherapy; 2 of 8 (25%) died during treatment, 6 of 8 (75%) achieved CR. None have relapsed, at a median duration of follow-up of 38 months. Neutropenic sepsis and subclinical doxorubicin cardiotoxicity at a mean cumulative dose of 63 mg/m2 were the principal toxicities. Our data indicate that aggressive chemotherapy is both feasible and effective in phenotypically monoclonal PTLD refractory to reduced immunosuppression. ProMACE-CytaBOM is well suited to cardiac recipients, minimizing doxorubicin exposure and obviating the need for concurrent immunosuppressives.
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