Casey L McAtee1, Netta Schneller2, Julienne Brackett2, M Brooke Bernhardt3, Eric S Schafer2. 1. Department of Pediatrics, Baylor College of Medicine, 1102 Bates St., Suite 1025, Houston, TX, 77030, USA. cxmcatee@texaschildrens.org. 2. Department of Pediatrics, Baylor College of Medicine, 1102 Bates St., Suite 1025, Houston, TX, 77030, USA. 3. Department of Pharmacy, Texas Children's Hospital, 6701 Fannin St., Houston, TX, 77030, USA.
Abstract
PURPOSE: Sinusoidal obstruction syndrome (SOS), also known as veno-occlusive disease, has been described following treatment of acute lymphoblastic leukemia (ALL) with the anti-metabolite 6-thioguanine (6-TG). Previous studies incorporating daily 6-TG into maintenance chemotherapy demonstrated a high incidence of SOS, typically presenting after prolonged exposures to 6-TG. 6-TG continues to be used as a single, 14-day burst during intensification; however, SOS associated with brief courses of 6-TG is poorly described. We aim to describe this rare though clinically significant phenomenon. METHODS: Children with 6-TG-related SOS were retrospectively identified from 680 de novo patients with ALL at Texas Children's Cancer Center over 8 years. Clinical characteristics and outcomes are described. RESULTS: Ten (1.5%) patients were identified with SOS. No predominant sex, ethnicity, or race was noted. SOS was diagnosed 16.5 (6-42) days from starting 6-TG. Isolated thrombocytopenia (IT) was noted in 9/10 patients and presented a median of 5 days prior to SOS. Refractoriness to platelet transfusions was noted in 8/10 patients, presenting a median of 2 days prior to SOS. Most patients were otherwise clinically stable outpatients upon presenting with IT or transfusion refractoriness. Fever was noted in 7/10 patients at diagnosis and 6/10 had documented or suspected infection within 14 days of SOS. Two patients died, while eight fully recovered. Intermediate thiopurine methyltransferase genotype was noted in 5/8 patients with data available. CONCLUSION: SOS following short courses of 6-TG in DI is clinically distinct from SOS following prolonged courses of 6-TG in maintenance, particularly in its early presentation and outcomes.
PURPOSE:Sinusoidal obstruction syndrome (SOS), also known as veno-occlusive disease, has been described following treatment of acute lymphoblastic leukemia (ALL) with the anti-metabolite 6-thioguanine (6-TG). Previous studies incorporating daily 6-TG into maintenance chemotherapy demonstrated a high incidence of SOS, typically presenting after prolonged exposures to 6-TG. 6-TG continues to be used as a single, 14-day burst during intensification; however, SOS associated with brief courses of 6-TG is poorly described. We aim to describe this rare though clinically significant phenomenon. METHODS:Children with 6-TG-related SOS were retrospectively identified from 680 de novo patients with ALL at Texas Children's Cancer Center over 8 years. Clinical characteristics and outcomes are described. RESULTS: Ten (1.5%) patients were identified with SOS. No predominant sex, ethnicity, or race was noted. SOS was diagnosed 16.5 (6-42) days from starting 6-TG. Isolated thrombocytopenia (IT) was noted in 9/10 patients and presented a median of 5 days prior to SOS. Refractoriness to platelet transfusions was noted in 8/10 patients, presenting a median of 2 days prior to SOS. Most patients were otherwise clinically stable outpatients upon presenting with IT or transfusion refractoriness. Fever was noted in 7/10 patients at diagnosis and 6/10 had documented or suspected infection within 14 days of SOS. Two patients died, while eight fully recovered. Intermediate thiopurine methyltransferase genotype was noted in 5/8 patients with data available. CONCLUSION:SOS following short courses of 6-TG in DI is clinically distinct from SOS following prolonged courses of 6-TG in maintenance, particularly in its early presentation and outcomes.
Authors: Nancy A Kernan; Paul G Richardson; Angela R Smith; Brandon M Triplett; Joseph H Antin; Leslie Lehmann; Yoav Messinger; Wei Liang; Robin Hume; William Tappe; Robert J Soiffer; Stephan A Grupp Journal: Pediatr Blood Cancer Date: 2018-06-06 Impact factor: 3.167
Authors: Joanna S Yi; Tiffany M Chambers; Kelly D Getz; Tamara P Miller; Evanette Burrows; Marla H Daves; Philip J Lupo; Michael E Scheurer; Richard Aplenc; Karen R Rabin; Maria M Gramatges Journal: Haematologica Date: 2022-05-01 Impact factor: 11.047