Treatment of Large B Cell Lymphoma in the Setting of High Bilirubin - Case Report and Review of the Literature.
Authors: Silbermins Damian , Scott Emma , Cohn Jeffrey 
Published: October 2019

Abstract
Introduction
We report a case of a patient with Large B Cell Lymphoma and liver involvement who presented with significant hyperbilirubinemia. After his disease progressed through cyclophosphimide, dexamethasone, and Rituximab, a novel regimen was developed that could be given at full doses despite his hepatic abnormalities.
Mr. H is a 57 year-old Vietnamese male without prior significant medical history. He presented with a 3 month history of 40 pound weight loss, nausea, vomiting, jaundice, abdominal pain and constipation.
The CT scan of the abdomen showed multiple hypodensities in the spleen and liver, with multiple nodes in the abdomen and retroperitoneal area. Initial laboratories are shown in Table 1.
A biopsy of a palpable left axillary lymph node revealed DLCL, B-Cell. An ERCP with sphinterectomy showed normal biliary and pancreatic system.
He was initially treated with cyclophosphamide (750mg/m2), dexamethasone and Rituximab (375mg/m2). Doxorubicin and vincristine were held due to the high bilirrubin.
One month later the patient was re-admitted with a new cervical and axillary adenopathy. His total bilirubin remained markedly elevated at 6.
Given his persistently abnormal liver function tests and progression of disease on Cyclophosphamide/Rituximab/Dexamethasone, an alternative regimen was required. We elected to utilize a regimen consisting of Ifosfamide (800 mg/m2/days 1–4), Mesna (800 mg/m2/days 1–4), Cisplatin (20 mg/m2/days 1–4, Gemcitabine (700 mg/m2 day 5), high dose steroids (dexamethasone 40mg daily x 5 days) and Rituximab (375mg/m2 day 1).
Following this chemotherapy, his liver function tests improved which allowed the resumption of standard chemotherapy. The patient has completed a full course of CHOP-R and is in a complete clinical remission one year from end of therapy.
DISCUSSION
To date, only one retrospective trial has analyzed the treatment of lymphoma in the setting of high bilirrubin. Ghobrial et al. performed a retrospective review of 41 patients with lymphoma, of whom 37 had Non-Hodgkin lymphoma. These patients were treated with mecholrethamine-based therapy as a bridge to conventional chemotherapy. About 50% of them had sufficient improvement to be changed to standard therapy.
Ifosfamide, an analog of cyclophosphamide was chosen as part of the regimen. Some of the most recent salvage chemotherapies for NHL contain ifosfamide, with overall response rates ranging from 32% to 72%. Although there have been reports of cholestasis when associated to etoposide, such effects were thought to be more related to the epipodophyllotoxin, and therefore only Ifosfamide was chosen for our patient.
Cisplatin has been shown to have modest single-agent activity against NHL, inducing remissions in approximately 20% of patients with advanced NHL, with no hepatotoxicity.
Gemcitabine, an analog of cytarabine, has shown activity in a variety of histological subtypes of non-Hodgkin Lymphoma as a single drug. Furthermore, its use in pancreatic cancer has demonstrated a fairly safe toxicity profile in regard to hyperbilirubinemia.
In conclusion, in the setting of high bilirrubin, the combination of Ifosfamide, Cisplatin, Dexamethasone, Gemcitabine and Rituximab may be an adequate alternative to CHOP-R in the initial curative management of patients with B-cell DLCL.
Laboratory Results Alkaline Phosphatase 1408 AST 156 ALT 103 Total Protein 5.2 Albumin 2.6 Total Bilirubin 14 Direct Bilirubin 7.3