REGIMEN-RELATED LIVER TOXICITY IN AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION

The incidence of hepatic veno-occlusive disease (VOD) varies in different series (1-65%), depending on the type of transplant and on the patients’ characteristics. Even in the setting of autologous HSTC, however, the frequency of this life threatening regimen-related toxicity is undetermined. We retrospectively analyzed the data of 165 consecutive patients transplanted between June 1995 and October 1999 at our Center. HBsAg and HCVAb positive patients were excluded. Diagnosis was: non-Hodgkin’s lymphoma (62), Hodgkin’s disease (11), multiple myeloma (20), leukemia (16), breast cancer (47), and others (9). Nineteen patients (7 MM, 8 BC, 3 OC, 1 HD) received double transplants. The source of hematopoietic stem cells was: BM (2%), PBPCs (86%), BM+PBPCs (6%), selected CD34+ cells (6%). The regimen was: BEAM (32%), Busulfan based regimens (11%), HD/L-PAM (13%), MTZ/L-PAM (9%), MTZ/TT/CY (13%), TT/L-PAM (17%), and other regimens (5%). The parameters we considered were: 1) bilirubin levels in the 4 weeks after transplant, 2) painful hepatomegaly, 3) ascites and/or unexplained weight gain. Other indices of liver damage (AST, ALT, -GT, etc.) were also considered. An increased bilirubin level above the base line was observed in most patients, with a median peak value of 0.8 mg/DL (mean 0.8, range 0.3-1.9). A transient increase in body weight (median increase 1.5%, mean 1.95%, range 0.5%-6.0%), that was promptly corrected by diuretics, was also observed in 60% of our patients. Nevertheless, no one of our patients met the commonly accepted criteria (Seattle and Baltimore criteria) for a clinical diagnosis of hepatic VOD. In only one patient with (MM) severe liver toxicity occurred 9 months after the second transplant, and multi-organ failure eventually developed. The conditioning regimen at the second transplant had been busulphan + L-PAM. This patient could have met the criteria for a clinical diagnosis of VOD, except for the late onset of the symptoms. Others have reported a higher incidence of hepatic VOD. This might be explained by the selection criteria of the patients in different series. In summary, in selected patients undergoing auto-HSC transplantation in the context of a front line treatment and receiving a variety of conditioning regimens, the frequency of hepatic VOD seems to be quite low.