P1879 - Sinusoidal Obstruction Syndrome in a Leukemia Patient Treated With Inotuzumab

Monday, October 25, 2021

10:30 AM – 4:15 PM PT

Location: Shoreline Exhibit Hall

Has Audio

Award: Presidential Poster Award

Presenting Author(s)

Shaleen Vasavada, MD

Baylor College of Medicine
Houston, TX, United States

Award: Presidential Poster Award

Shaleen Vasavada, MD¹, Hao Chi Zhang, MD²
¹Baylor College of Medicine, Houston, TX; ²University of Texas MD Anderson Cancer Center, Houston, TX

Introduction: We report a patient without history of hematopoietic stem cell transplant (HSCT) who was treated with Inotuzumab ozogamicin (InO) for relapsed B-cell precursor acute lymphoblastic leukemia (B-ALL) and developed sinusoidal obstruction syndrome, also known as veno-occlusive disease (VOD/SOS).

Case Description/Methods: A 66-year-old woman with relapsed B-ALL presented with progressive anasarca for 4 weeks. She had been treated with InO and ponatinib for 5 months. Over the previous month, the patient noted dyspnea on exertion, progressive abdominal distension, bilateral lower extremity edema and a 4-kg weight gain. On physical exam, vital signs were normal with a non-tender, distended abdomen associated with fluid wave but no obvious jaundice. Lab results are shown in Table 1. Serologies for acute viral entities (hepatitis A, B, & C) were negative. Abdominal ultrasound demonstrated a liver span of 15.5 cm with normal echogenicity without focal mass lesion and a patent portal vein. Deferring liver biopsy, empiric treatment was initiated with intravenous defibrotide for the high probability of VOD/SOS. After completing 21 days of defibrotide, clinical signs of edema improved; however, she eventually succumbed to her illness from leukemia within 3 months.

Discussion: The diagnostic criteria for VOD/SOS includes hepatomegaly, weight gain, and hyperbilirubinemia following HSCT. InO, a humanized monoclonal antibody against CD22, can cause VOD/SOS in up to 14% of patients. This suggests the criteria for VOD/SOS should encompass clinical scenarios other than HSCT, such as drug-induced variations. Furthermore, treatment was administered without a biopsy. The risks of an invasive procedure and cytopenic states of leukemia patients may be prohibitive towards undergoing liver biopsy. Therefore, empiric treatment for VOD/SOS based on strong clinical suspicion is a viable option since the consequences of not treating could be morbid. Originally approved in 2016 by the FDA solely for the purpose of treating VOD/SOS following HSCT, defibrotide is a mixture of single-stranded oligonucleotides that is thought to reduce endothelial-cell activation and stabilize sinusoidal endothelial cells. To this date, there is no systematic review of defibrotide’s use in drug-induced VOD/SOS. Further studies should clarify the novel role of empiric treatment, without biopsy, in patients with a high clinical suspicion for InO-induced VOD/SOS.

Variable	Baseline	Initial Presentation	Day 2 of defibrotide	Day 13	Day 21	6 days after completion	Reference Range (units), adults
ALT	23	46	44	40	34	26	≤33 (U/L)
AST	26	60	57	41	52	27	≤32 (U/L)
ALP	73	505	412	285	252	213	35-104 (U/L)
Total Bilirubin	0.3	3.0	1.6	1.7	1.4	1.5	≤1.2 (mg/dL)
Direct Bilirubin	0.1	2.1	1.1	1.1	0.7	0.9	≤0.3 (mg/dL)
GGT	-	-	166	-	-	-	5-36 (U/L)
Albumin	3.6	3.2	-	2.3	2.8	2.6	3.5 - 5.2 (g/dL)
INR	0.94	0.95	1.05	1.06	-	1.01	0.90 - 1.10

Table: Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; ALP, alkaline phosphatase; GGT, gamma-glutamyl transpeptidase; INR, international normalized ratio

Disclosures:

Shaleen Vasavada indicated no relevant financial relationships.

Hao Chi Zhang indicated no relevant financial relationships.

Shaleen Vasavada, MD¹, Hao Chi Zhang, MD². P1879 - Sinusoidal Obstruction Syndrome in a Leukemia Patient Treated With Inotuzumab, ACG 2021 Annual Scientific Meeting Abstracts. Las Vegas, Nevada: American College of Gastroenterology.