P0802 - Chronic Lymphoid Leukemia With Extensive Liver Infiltration in the Absence of Leukemic Transformation

William D. Davis, DO¹, Megan E. Murphy, MD², Annie Kruger, MD, PhD², James H. Lewis, MD^2
1MedStar Georgetown University Hospital, Washington, DC; ²Georgetown University Hospital, Washington, DC

Introduction: Chronic lymphoid leukemia (CLL) is the most common hematologic cancer diagnosed in the elderly. Its association with liver dysfunction secondary to leukemic infiltration ranges from mild elevations in liver enzymes (LE) to acute liver failure. Severe hepatic infiltration is typically associated with acute leukemic transformation. Here we report an atypical manifestation of CLL with rising LE and white blood cell (WBC) count mimicking leukemic transformation.

Case Description/Methods: 62-year-old male with history of CLL not on therapy presented to clinic for abnormal LE and rising leukocytosis. Patient reported fatigued, jaundice, right upper quadrant pain and 25lb weight loss over five months attributed to dietary modifications. Patient reported taking glimepiride, atorvastatin and herbal supplements (GNC50+ multivitamin, fertility and prostate multivitamin) that were stopped five months prior to encounter due to concerns of drug-induced liver injury (DILI). Labs were significant for absolute lymphocytosis >53,000/uL, AST 156U/L, ALT 336U/L, total bilirubin 4.4 mg/dl, direct bilirubin 3.57mg/dl and gamma-glutamyl transferase of 94U/L from previously normal LE. Additional work up was negative for viral and autoimmune etiologies. NASH Fibrosure was consistent with F4 Fibrosis. Computer tomography (CT) of abdomen did not demonstrate fatty changes but did show significant abdominal lymphadenopathy.

Patient was hospitalized for rapidly rising WBC and LE. Abdominal ultrasound doppler showed patent liver vasculature. Transjugular liver biopsy was negative for acute leukemic transformation, but did identify extensive, >60% sinusoidal infiltration by CLL with hepatic venous pressure gradient (HVPG) of 11 mmHG attributed to periportal and peripancreatic adenopathy observed on CT imaging (Imaging A-D). Patient was initiated on Venetoclax and Obinutuzumab as an outpatient.

LE peaked two months after chemotherapy initiation. Liver synthetic function remained normal (Table 1).

Discussion: After ruling out DILI with failed improvement upon discontinuation of suspected agents and liver biopsy, extensive CLL extranodal liver involvement was attributed to have caused liver dysfunction and subsequent portal hypertension. Severe pattern of involvement is rare without Richter Transformation, which can be seen in 8% of CLL patients. Due to severe pattern of liver infiltration, worsening LE, portal hypertension, and hepatosplenomegaly it was ultimately decided to start patient on chemotherapy.


Figure: Image A:CT abdomen and pelvis with IV contrast depicting an enlarged 33.4x42.9mm periportal lymph node
Image B: CT abdomen and pelvis with IV contrast depicting 11.7x18.3mm pancreatic lymph node
Image C: : H&E (400x) section demonstrates an atypical lymphoid follicle surrounding bile ductules, with adjacent liver parenchyma. Characteristic immunohistochemical staining of the neoplastic cells shows positivity for CD20 (dim), CD5, CD23, and is negative for CD3
Image D: ZAP 70 (400x) staining (brown) of neoplastic cells has been associated with a poor prognosis

Date	White Blood cell count (K/uL)	AST (units/L)	ALT (units/L)	Alkaline Phosphatase (units/L)	Total Bilirubin (mg/dL)	INR
1/8/18	26.9	23	25	52	0.7
11/8/19	39.5	38	54	60	0.7
1/14/20	58.2	30	44	71	0.6
3/6/20		88	214	67	1.3
4/29/20		155	315	92	3.9
5/18/20*	50.9	165	292	111	5.8	1.0
7/6/20**	72.4	165	303	121	7.1
7/14/20***	6.9	412	759	139	11
5/18/21****	2.6	42	88	110	1.2

Table: Title: Patient laboratory information from date of diagnosis to most recent outpatient follow up.
Footnote: *Represents laboratory data for time of hospital admission for elevated liver enzyme work up
**Represents the laboratory data prior to initiation of chemotherapy
***Represents peak liver enzyme abnormality
****Represents most recent outpatient follow up laboratory data


Disclosures:
William Davis indicated no relevant financial relationships.
Megan Murphy indicated no relevant financial relationships.
Annie Kruger indicated no relevant financial relationships.
James Lewis indicated no relevant financial relationships.


William D. Davis, DO¹, Megan E. Murphy, MD², Annie Kruger, MD, PhD², James H. Lewis, MD². P0802 - Chronic Lymphoid Leukemia With Extensive Liver Infiltration in the Absence of Leukemic Transformation, ACG 2021 Annual Scientific Meeting Abstracts. Las Vegas, Nevada: American College of Gastroenterology.