Hospital Pharmacy - June 2018 - 195

195

Ali et al
rituximab to standard cytotoxic therapy for DLBCL has
improved the outcome at the expense of reactivating hepatitis
B virus (HBV) in lymphoma patients.5-7 Not only has the
reactivation of HBV been reported; rather, there are case
reports and case series suggesting that rituximab (R) also
increases the risk of viral infections. HBV infection is a global
infective condition affecting almost one-third of the world's
population. Seventy-five percent of 350 million people who
have chronic HBV infection live in Southeast Asia and the
Western Pacific regions.8-10 It is endemic in Pakistan affecting
approximately 9 million people and the rate of infection is
steadily increasing.11
The clinical picture and outcome are further compromised
by febrile neutropenia (FN). FN is one of the major toxicity
reported in DLBCL patients treated with R-CHOP. It is
reported in number of studies that most cases of FN occur
during the first cycle of R-CHOP.12 According to National
Comprehensive Cancer Network (NCCN) and European
Organization for Research and Treatment of Cancer
(EORTC) guidelines, R-CHOP is an intermediate risk for
FN. The guidelines also recommended that patient's own
factors, chemotherapy regimen, and prophylactic treatment
with granulocyte colony-stimulating factor (G-CSF) should
also be taken into the equation of risk assessment for FN.9,10,13
The aim of this study was to determine the incidence of
HBV and hepatitis C virus (HCV) infection and FN in
DLBCL patients treated with R-CHOP and to compare it
with the patients receiving the conventional cytotoxic treatment, ie, cyclophosphamide, hydroxyrubicin, Oncovin, and
prednisolone (CHOP). We also aimed to establish the relationship between the incidence of viral infection (ie, HBV or
HCV) and FN.

Method
This was an institutional approved study in which patient
records from a private hospital, specialized in hematology
and oncology (Karachi, Pakistan), were reviewed retrospectively from 2014 to 2016. Patients aged above 18 years
with known diagnosis of DLBCL who underwent CHOP-21
or R-CHOP-21 chemotherapy regimen were included.
Baseline blood chemistry and liver function tests along with
the data regarding HBV (hepatitis B surface antigen
[HBsAg], hepatitis B surface antibody [anti-HBs]), HCV
(antibody anti-HCV), and FN were collected from patient
records. The collected data were subjected to statistical
analysis using SPSS.

Results
In total, 35 cases of DLBCL were treated during a 3-year
period (ie, from 2014 to 2016), of which 16 were on CHOP-21
regimen whereas 19 were treated with R-CHOP-21. Mean
age of the patients on either treatment was 53.15 ± 13 years.
Twenty-five patients out of 35 were male. From the data, it

was gathered that patient were followed up for 6 months post
treatment. Blood chemistry and liver function test were done
both pretreatment and on the beginning of every cycle (Table
1). However, none of the patients neither had their baseline
viral screening done nor were they given G-CSF within 7
days after the administration of chemotherapy, which is a
recommended international practice.
Of the 19 patients who underwent R-CHOP chemotherapy,
only 2 (10%) patients were HBsAg reactive. Before commencing the second cycle, 2 (10%) cases reported to hospital
with fever and had hematological (low neutrophil count) and
microbiological (Escherichia coli) proven FN. The incidence
of HBV infection post treatment was lower in group treated
with CHOP (1 patient showed HBsAg reactivity). The prevalence of both HBV infection and FN was 8.57% in our cohort.
HCV reactivity was not found in either group (Table 2). The
baseline and posttreatment blood chemistry showed no significant difference except for alkaline phosphatase (P <
.002).

Discussion
To the best of our knowledge, this was one of its kind studies
performed to investigate the incidence of HBV, HCV, and FN
in DLBCL patient on CHOP or R-CHOP therapy. The
research was conducted in a specialty tertiary care center
offering therapeutic services in heme-oncology. Reactivation
of HBV is commonly reported in HBsAg-positive patients
undergoing immunosuppressive anticancer therapy. It is
strongly recommended in literature to routinely screen NHL
patients for HBsAg who are residing in HBV endemic areas
before commencing cytotoxic chemotherapy. The screening
recommendation is to identify the high-risk patient for prophylactic antiviral treatment and to reduce the incidence and
morbidity associated with reactivation of HBV.14
The findings of the study revealed that incorporation of
rituximab significantly increased the incidence of HBV,
whereas HCV incidence was reported in none. Fifty-four
percent (19 of 35) of patients enrolled in the study were on
R-CHOP and 45.7% (16 of 35) were on CHOP treatment. Of
the 19, 2 (10.5%) showed reactivity for HBsAg, whereas
6.25% (1 of 16) had substantive antibody titers for HBsAg to
show positive reactivity. At present, no screening or prophylactic antiviral treatment is recommended in our practice.
However, our study finding strongly warrants not only revision
of the institutional policy in this regard; rather, it requires
conducting the study more thoroughly with ample sample
size to confirm our present findings.
Neutropenia with fever is one of the complications of
myelosuppressive chemotherapy which accounts for considerable morbidity and mortality and also results in hospitalization. According to the current guideline, chemotherapy
regimens with occurrence rate of FN are classified as high
(>20%), intermediate (10%-20%), and lower (<10%).
Though these classifications of chemotherapy regimens are

Table of Contents for the Digital Edition of Hospital Pharmacy - June 2018