Jan Kamelander

Successful treatment of steroid-refractory hepatitic variant of liver graft-vs-host disease with pulse cyclophosphamide

OBJECTIVE Corticosteroid-resistant graft-vs-host disease (GVHD) is difficult to manage and is associated with high morbidity and mortality. No standard treatment exists. We have previously seen good results with pulse cyclophosphamide (Cy) in the treatment of liver GVHD in contrast to gastrointestinal GVHD, and here we report results of pulse Cy protocol in the treatment of steroid-refractory hepatitic variant of liver GVHD, with no association to the gut. MATERIALS AND METHODS Cy was infused at a dose of 1,000 mg/m(2). Twenty-nine cyclophosphamide administrations were given to 21 patients. Median time of GVHD onset and Cy administration after transplantation, or donor lymphocyte infusion, were 58 and 69 days, respectively. RESULTS Eleven patients (52%) achieved complete remission and 6 patients (29%) achieved partial remission. Four patients (19%) did not respond, however, their condition stabilized and, upon additional therapy, three achieved partial remission and one complete remission. Overall survival of all 21 patients is 86%, with median and maximal follow-up of 33 and 81 months, respectively. Toxicity was mild and easily manageable without influencing chimerism or disease status. CONCLUSIONS Pulse Cy seems to be an effective treatment for steroid-refractory hepatitic variant of liver GVHD with a good toxicity profile, which may favor its use instead of drugs with more pronounced immunosuppressive effects.

Kinetics of bilirubin and liver enzymes is useful for predicting of liver graft-versus-host disease

Graft-versus-host disease (GVHD) is the most frequent complication after allogeneic hematopoietic cell transplantation. We analyzed the kinetics of bilirubin and liver enzymes in 47 cases with liver GVHD and in 47 cases without GVHD after allogeneic transplantation for various hematological malignancies. The duration of an liver GVHD episode (LGVHD) was defined as the interval from the point when the criteria of LGVHD were met to the decrease to < 2 upper normal limit (UNL) for aminotransferases or bilirubin < 34 μmol/l for bilirubin. The imminent LGVHD episode was defined as the interval from the start of continuous increase (≥ 3 consecutive rising values) of bilirubin and liver enzymes above UNL to the point of LGVHD diagnosis.The number of imminent LGVHD episodes, and median length in days were as follows: bilirubin (39;5), ALT(28;12), AST(9;12), GGTP(34;9), and ALP(13;14). Statisticallly significant associations between asymptomatic continuous increase of bilirubin, ALT, and GGTP and later liver GVHD manifestation were found (p=0.004, p=0.008, p=0.005, respectively). The asymptomatic continuous increase in bilirubin, ALT, and GGTP occurred at a median of 5, 12, and 9 days before liver GVHD episode, respectively. In the control group without GVHD, median levels of bilirubin and liver enzymes were within normal limits and no continuous increase was observed.Kinetics of bilirubin and liver enzymes is useful for predicting of liver GVHD. A continuous increase of bilirubin and/or ALT, GGTP before the standard liver GVHD criteria are met can be a sign of coming liver GVHD.