Jeff Hosry

Concomitant use of direct-acting antivirals and chemotherapy in hepatitis C virus-infected patients with cancer.

Antiviral therapy improves hepatic outcomes in hepatitis C virus (HCV)‐infected cancer patients. However, such patients are not treated simultaneously with antivirals and chemotherapy, owing to overlapping toxicities with previous standard of care treatment of pegylated interferon and ribavirin.

Antiviral therapy improves overall survival in hepatitis C virus-infected patients who develop diffuse large B-cell lymphoma

Chronic Hepatitis C virus (HCV) infection is associated with increased incidence of non‐Hodgkin lymphoma. Several studies have demonstrated regression of indolent lymphoma with antiviral therapy (AVT) alone. However, the role of AVT in HCV‐infected patients with diffuse large B‐cell lymphoma (DLBCL) is unclear. We therefore analyzed AVTs impact on oncologic outcomes of HCV‐infected patients (cases) who developed DLBCL. Cases seen at our institution (June 2004–May 2014) were matched with uninfected counterparts (controls) and then divided according to prior AVT consisting of interferon‐based regimens. We studied 304 patients (76 cases and 228 controls). More cases than controls had extranodal (79% vs. 72%; p = 0.07) and upper gastrointestinal (GI; 42% vs. 24%; p = 0.004) involvement. Cases never given AVT had DLBCL more refractory to first‐line chemotherapy than that in the controls (33% vs. 17%; p = 0.05) and exhibited a trend toward more progressive lymphoma at last examination compared to controls (50% vs. 32%; p = 0.09) or cases given AVT (50% vs. 27%; p = 0.06). Cases never given AVT had worse 5‐year overall survival (OS) rates than did the controls (HR, 2.3 [95% CI, 1.01–5.3]; p = 0.04). Furthermore, AVT improved 5‐year OS rates among cases in both univariate (median [Interquartile range]: 39 [26–56] vs. 16 [6–41] months, p = 0.02) and multivariate analyses (HR = 0.21 [95% CI, 0.06–0.69]; p = 0.01). This study highlights the negative impact of chronic HCV on survival of DLBCL patients and shows that treatment of HCV infection is associated with a better cancer response to chemotherapy and improves 5‐year OS.

Hepatitis C virus reactivation in patients receiving cancer treatment: A prospective observational study

Hepatitis C virus (HCV) reactivation in patients receiving cancer treatment has been reported in retrospective studies. We sought to determine prospectively the incidence, predictors, and clinical significance of HCV reactivation during cancer treatment. HCV‐infected patients receiving cancer treatment at our institution between November 2012 and July 2016 were studied. Reactivation was defined as an increase in HCV‐RNA ≥1 log10 IU/mL over baseline and hepatitis flare as an increase in alanine aminotransferase to ≥3 times the upper limit of normal. One hundred patients were studied, 50 with hematologic malignancies and 50 with solid tumors. Reactivation occurred in 23 (23%) patients, including 18 (36%) patients with hematologic malignancies and 5 (10%) patients with solid tumors. In univariate analysis, patients with reactivation were more likely than those without reactivation to have prolonged lymphopenia (median, 95 versus 22 days; P = 0.01) and to have received rituximab (44% versus 9%; P < 0.0001), bendamustine (22% versus 0%; P < 0.001), high‐dose steroids (57% versus 21%; P = 0.001), or purine analogs (22% versus 5%; P = 0.02). Rituximab (odds ratio = 9.52; P = 0.001), and high‐dose steroids (odds ratio = 5.05; P = 0.01) retained significance in multivariable analysis. Of the 23 patients with reactivation, 10 (43%) had hepatitis flare. No patient with reactivation experienced liver failure or liver‐related death within 36 weeks after initiation of cancer treatment. Fourteen patients with hepatitis flare, six of whom had reactivation, required discontinuation or dose reduction of cancer treatment. Conclusion: HCV reactivation occurred in 23% of HCV‐infected patients receiving cancer treatment, and most had an unremarkable clinical course. However, reactivation can affect the cancer treatment plan. Our findings suggest that HCV infection should not contraindicate cancer therapy and infected patients should have access to multiple cancer treatments with close monitoring while receiving regimens associated with HCV reactivation. (Hepatology 2018;67:36‐47).

Clinicopathologic characteristics and outcomes of transformed diffuse large B-cell lymphoma in hepatitis C virus-infected patients

Hepatitis C virus (HCV) causes a chronic but curable infection associated with the development of marginal zone lymphoma (MZL) and diffuse large B‐cell lymphoma (DLBCL). Preliminary data have shown frequent transformation of indolent lymphoma to DLBCL in HCV‐infected patients. To compare their clinicopathologic characteristics and oncologic outcomes, we reviewed the medical records and pathology reports of HCV‐infected and uninfected patients with DLBCL that transformed from indolent lymphoma seen at The University of Texas MD Anderson Cancer Center (June 2004 to May 2015). To identify predictors of DLBCL relapse, patients with relapse after first‐line chemotherapy were compared with those without it using univariate and logistic regression analyses. Compared with the uninfected patients (n = 63), HCV‐infected patients (n = 21) were younger (median age =54 years [interquartile range= 49–62 years] vs. 62 years [53–66 years]; p = 0.01) and more often had advanced DLBCL (Ann Arbor stage 3–4; 95% vs. 76%; p = 0.05). Immunophenotypically, more HCV‐infected than uninfected patients had CD10‐negative B cells (76% vs. 43%; p = 0.008), CD5‐positive B cells (39% vs. 7%; p = 0.004) and activated B‐cell phenotypes (57% vs. 31%; p = 0.07). Comparison of the patients who had relapse after first‐line chemotherapy (n = 42) and those who did not (n = 40) revealed that having CD5‐positive B cells was the only factor associated with DLBCL relapse in multivariate analysis (odds ratio= 10.7; p = 0.02). HCV‐infected patients with transformed DLBCL have unique clinicopathologic characteristics that make their lymphoma difficult to treat, potentially leading to unfavorable outcome. The impact of HCV eradication should be explored in such patients.

Development of non-Hodgkin lymphoma as a second primary cancer in hepatitis C virus-infected patients with a different primary malignancy

This study will be presented in part at the 52nd Annual Meeting of American Society of Clinical Oncology (ASCO), 3–7 June 2016, Chicago, IL. Chronic hepatitis C virus (HCV) infection affects more than four million people in U.S.A. (1.6% of the population).[1] The carcinogenic effect of HCV is well documented, with hepatocellular carcinoma (HCC) and non-Hodgkin lymphoma (NHL) the most common cancers associated with chronic infection.[2] HCC may develop as a second primary cancer (SPC) in up to 7% of HCVinfected patients with a nonliver first primary cancer (FPC).[3] However, reports of the development of NHL as a SPC in patients with a different FPC are lacking. In the present study, we sought to describe the characteristics of NHL in chronically HCV-infected patients with a different FPC and identify predictors for its development. In this case–control study, we identified patients with chronic HCV infection (positive anti-HCV and detectable HCV RNA in the serum) in whom NHL developed as a SPC in the setting of a different FPC and were seen at our institution from January 2008 through December 2015. The process followed to select patients for the study is depicted in Figure 1. The study was approved by the MD Anderson Institutional Review Board. We extracted data on NHL characteristics at the time of cancer diagnosis and characteristics of FPCs. Additionally, we analyzed data on virologic parameters such as viral genotype and duration of viremia. Non-Hodgkin lymphoma was diagnosed using computed tomography and/or biopsy. NHL was classified according to the 2008 World Health Organization guidelines and HCV-associated NHL was identified as previously described.[4] The Ann Arbor staging system was used to determine the stage and prognosis of NHL. Sustained virological response (SVR) was defined as an absence of HCV RNA in the serum 24 weeks after completion of antiviral treatment (AVT), the treatment endpoint used with interferon-based regimens (the most common therapy used in our study patients).[5] The duration of HCV infection was measured with a starting point of diagnosis of FPC. Endpoints included dates of SVR, death and last follow-up. Descriptive statistics were used to characterize the study population. Chronically HCV-infected patients with a FPC in whom NHL developed as a SPC (cases) were matched at a 1:3 ratio with HCV-infected cancer patients who did not develop any SPC (controls), based on their FPC. Matched analysis was conducted and p values <0.05 were considered statistically significant. One hundred seventeen patients with HCV-associated NHL were seen at MD Anderson during the study period. Among them, 21 (18%) developed NHL as a SPC (cases) and underwent further analysis. The median patient age at the time of diagnosis of SPC was 63 years (interquartile range: 52–88 years). Eleven patients (52%) had a family history of cancer, but only one patient (5%) had a family history of lymphoma in particular. The types of NHL were diffuse large B cell lymphoma (57%), marginal zone B cell lymphoma (24%), mantle cell lymphoma (14%) and lymphoplasmacytic lymphoma (5%). The distribution of Ann Arbor stage was almost even among cases: stage 2 (38%), stage 3 (33%) and stage 4 (29%). NHL was diagnosed at a median of 6 years (interquartile range, 3–11 years) after the FPC diagnosis. NHL as a SPC was diagnosed as an incidental finding in 11 cases (52%). First primary cancers were mainly solid tumors (81%), mostly involving the genitourinary (38%) or respiratory (19%) tracts (Table 1). Four cases (19%) had a hematologic malignancy as FPC: three of them (3/4; 75%) with Hodgkin disease and one (1/4; 25%) with chronic lymphocytic leukemia. At the time of diagnosis of NHL, 11 cases (52%) had their FPC in complete remission and 9 (43%) had progressive disease. The most common chemotherapeutic agents administered were mitotic inhibitors [paclitaxel (3/9; 33%)], antimetabolites [5-flurouracil, gemcitabine (3/9; 33%)] and alkylating agents

Universal screening for hepatitis C: A needed approach in patients with haematologic malignancies

There have been no large studies on the prevalence of hepatitis C virus antibody (anti-HCV) and the optimal HCV screening strategy in patients with hematologic malignancies and hematopoietic cell transplant (HCT) recipients. On the basis of the limited available evidence, the American Society for Blood and Marrow Transplantation and European Conference on Infection in Leukemia recommend universal screening. We aimed to determine the prevalence of anti-HCV and to compare the effectiveness of universal HCV screening versus risk-factor-based and 1945-1965 birth-cohort-based screening at the largest tertiary cancer center in the United States. In this cross-sectional study, we included all patients with hematologic malignancies who were routinely tested for anti-HCV at their initial visit to The University of Texas MD Anderson Cancer Center from June 2004 through May 2014. Birth cohort and HCV risk factors were identified by chart review. The anti-HCV prevalence was 2.1% (283/13,718). We excluded 141 patients with a known history of HCV infection and further analyzed the remaining 142 patients with newly diagnosed anti-HCV. Of these 142 patients, 98 (69%) were born during 1945-1965, and 24 (17%) had at least one HCV risk factor identified by primary hematologist-oncologists. Almost one-third of the patients with newly diagnosed anti-HCV (42/142; 30%) did not belong to the 1945-1965 birth cohort or have HCV risk factors.In conclusion, birth cohort-based and risk factor-based screening would have missed one-third of HCV-infected cancer patients in this series. Universal screening appears necessary for patients with hematologic malignancies and HCT recipients. This article is protected by copyright. All rights reserved.