Impact of treatment‐related liver toxicity on the outcome of HCV‐positive non‐Hodgkin's lymphomas

Abstract

We studied 160 Hepatitis C virus (HCV)-positive patients with NHL (59 indolent NHL, 101 aggressive). Median age was 67 years. HCV-RNA was present in 146. HBsAg was positive in seven patients. At diagnosis, ALT value was above UNL in 67 patients. One hundred and twenty patients received an anthracycline-based therapy, alkylators, 28 received chemotherapy plus rituximab. Cytotoxic drugs dose was reduced in 63 patients. Among 93 patients with normal ALT at presentation, 16 patients developed WHO grade II-III liver toxicity. Among 67 patients with abnormal ALT, eight patients had a 3.5 times elevation during treatment. Among 28 patients treated with rituximab and chemotherapy, five patients (18%) developed liver toxicity. Thirty four patients (21%) did not complete treatment (eight for liver toxicity). Median progression-free survival (PFS) for patients who experienced liver toxicity is significantly shorter than median PFS of patients without toxicity (respectively, 2 years and 3.7 years, P 5 0.03). After a median F-UP of 2 years, 32 patients died (three for hepatic failure). A significant proportion of patients with HCV1 NHL develop liver toxicity often leading to interruption of treatment. This could be a limit to the application of immunochemotherapy programs. HCV1 lymphomas represent a distinct clinical subset of NHL that deserves specific clinical approach to limit liver toxicity and ameliorate survival. Am. J. Hematol. 85:46-50, 2010. V

Outcome prediction of diffuse large B-cell lymphomas associated with hepatitis C virus infection: a study on behalf of the Fondazione Italiana Linfomi

“…8,10,12,15,17 In our study, the only risk factor for severe hepatotoxicity was an increase in base-line value of ALT, similar to findings in the Japanese study. 3 So far, only a few studies have evaluated the prognosis of HCV-positive DLBCL.…”

“…8 In fact, we did not record any difference in terms of severe hepatotoxicity between the patients treated with R-CHOP and those treated with CHOP, while, after adjusting by prognostic factors, patients treated with R-CHOP displayed a better OS and PFS. Interestingly, in the subgroup of patients monitored with viremia, the viral load invariably increased after treatment with R-CHOP (or CHOP), in agreement with the findings of Ennishi et al 3 However, we did not find any clear direct relation between the increase in HCV-RNA and severe hepatotoxicity.…”

“…Interestingly, in the subgroup of patients monitored with viremia, the viral load invariably increased after treatment with R-CHOP (or CHOP), in agreement with the findings of Ennishi et al 3 However, we did not find any clear direct relation between the increase in HCV-RNA and severe hepatotoxicity. The interplay between HCV-RNA and transaminases in HCV-positive NHL during (immuno-)chemotherapy has been analyzed only in a limited number of patients in a few previous studies, 3,[8][9][10][11][12][13][14][15] with conflicting conclusions. While small case series suggested that HCV-RNA peak may precede or coincide with the development of an ALT flare, 11,13 as for HBV, 16 in the majority of the reports, HCV-RNA seems to behave irrespective of ALT levels and, therefore, does not …”

Antiviral therapy is associated with a better survival in patients with hepatitis C virus and B‐cell non‐Hodgkin lymphomas, ANRS HC‐13 lympho‐C study

“…There is a two-to four-fold increased risk of developing B-NHL among HCV-positive patients [1][2][3][4]. In comparison to their negative counterparts, HCV-associated B-NHL (i) are more often marginal zone lymphomas (MZL) and diffuse large B-cell lymphomas (DLBCL) [4], (ii) often display extranodal localization [3], (iii) and have higher rates of liver toxicity after treatment by chemotherapy [5][6][7][8]. HCV-associated lymphomas have also been shown to be frequently associated with type II mixed cryoglobulinemia (MC) [9,10], which are immunoglobulin complexes containing both a polyclonal IgG and a monoclonal IgM rheumatoid factor (RF) directed against the IgG.…”

Hepatitis B and C Seroprevalence in Solid Tumors - Necessity for Screening During Chemotherapy

“…There are conflicting evidence about the patients with HCV positivity and undergoing chemotherapy. Besides the studies that reported only mild-moderate elevations in liver enzymes of HCV positive patients with hematological malignancy undergoing chemotherapy (Zuckerman et al, 1998), in a recent review of 160 non-Hodgkin lymphoma patients with chronic hepatitis C, it was reported that 15% of them had significant liver toxicity (Arcaini et al, 2010). Also in diffuse large B-cell lymphoma patients, it was shown that, overall survival was significantly worse in the patients with chronic HCV infection than those without HCV infection (at a median follow up of two years overall survival rates were 56% and 80% respectively and p 0.02) (Besson et al, 2006).…”