1.
Incidence and Risk Factors of Early Onset VOD/SOS Differ in Younger vs Older Adults After Stem Cell Transplantation
Marcoux, C., Saliba, R. M., Wallis, W., Khazal, S. J., Ragoonanan, D., Rondon, G., Tewari, P., Popat, U. R., Oran, B., Olson, A. L., et al
Blood advances. 2024
Abstract
Veno-occlusive disease (VOD) is a rare but potentially life-threatening complication following allogeneic hematopoietic stem cell transplantation (allo-SCT). While increasing awareness and modern transplant techniques have mitigated risk, the interaction of historic risk factors in the current era with post-transplant cyclophosphamide (PTCy) is unknown. We performed a retrospective single center analysis of adult patients 18 years or older undergoing allo-SCT (N=1561) using predominately PTCy as GVHD prophylaxis (72%). We found a higher rate of VOD at 16.8% (20/119) in those aged ≤ 25 years compared to 3.8% (55/1442) in those >25 years, with unique predictors of VOD within each cohort. Multivariate classification and regression tree (CART) analysis confirmed age as the primary independent determinant of the rate of VOD. Within patients aged 18-25 years, disease risk index (DRI) (31% with high/very high DRI vs 12% low/intermediate DRI; p=0.03) and prior lines of chemotherapy (24% with >1 vs 6% with ≤1, p=0.03) were the strongest predictors of VOD. Incidence of VOD in patients > 25 years of age consistently ranged between 3-5% across most risk factors evaluated, with only hepatic factors (baseline elevation of bilirubin, aspartate transferase (AST), alanine aminotransferase (ALT)) or gemtuzumab exposure associated with increased rates of VOD. There was no significant difference in rates of VOD in those receiving PTCy compared to those receiving alternate GVHD prophylaxis. Our data highlight the differences in incidence and predictors in VOD between younger (≤25) and older (>25) adults undergoing allo-SCT.
2.
Improved detection of sinusoidal obstructive syndrome using pediatric-AYA diagnostic criteria and severity grading
Ragoonanan, D., Khazal, S. J., Wang, J., Payne, A., Kohorst, M., Harden, A., Tewari, P., Petropoulos, D., Shoberu, B., Kebriaei, P., et al
Bone marrow transplantation. 2020
Abstract
New diagnostic criteria and severity grading for sinusoidal obstructive syndrome (SOS) among pediatric and adolescent young adult (AYA) patients have been recently endorsed by international consensus. The extent to which these have been adopted in the US remains unclear. We sought to assess the potential impact via retrospective application of these criteria among patients treated at a large academic center in the United States. This is a single center retrospective study of pediatric-AYA patients who underwent hematopoietic cell transplantation (HCT) between July 2009 and 2019. The incidence of SOS was assessed using historic Baltimore and Seattle diagnostic criteria and compared with more recent guidelines (pEBMT) as proposed by the Paediatric Diseases Working Party of the European Society for Blood and Marrow Transplantation. Among 226 patients, application of the pEBMT diagnostic criteria was associated with a higher incidence (15.9%) and earlier time to diagnosis of SOS (by 2.5-3 days) compared with the modified Seattle (12.3%), and Baltimore (6.6%) criteria, respectively. The pEBMT criteria were sensitive and highly specific. Refractory thrombocytopenia was present in 75% of patients at diagnosis. Approximately 61% of patients with SOS were anicteric at diagnosis, though the majority (94.4%) developed hyperbilirubinemia as SOS progressed over a median time of 4 (1-57) days. Application of pEBMT criteria may have resulted in earlier indication for definitive treatment by 3 days. Timely diagnosis and administration of definitive treatment of SOS has been associated with improved outcomes. Prospective studies may better characterize the risk factors and natural course of SOS using pEBMT criteria.
3.
Diagnosis, grading, and treatment recommendations for children, adolescents, and young adults with sinusoidal obstructive syndrome: an international expert position statement
Mahadeo, K. M., Bajwa, R., Abdel-Azim, H., Lehmann, L. E., Duncan, C., Zantek, N., Vittorio, J., Angelo, J., McArthur, J., Schadler, K., et al
The Lancet. Haematology. 2019
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Editor's Choice
Abstract
Sinusoidal obstructive syndrome, also known as hepatic veno-occlusive disease, is a potentially life-threatening complication that occurs in children undergoing haemopoietic stem-cell transplantation (HSCT). Differences in the incidence of genetic predisposition and clinical presentation of sinusoidal obstructive syndrome between children and adults have rendered the historical Baltimore and Seattle diagnostic criteria insufficient for children. In 2017, the European Society for Blood and Marrow Transplantation (EBMT) proposed the first paediatric diagnostic and severity grading guidelines for sinusoidal obstructive syndrome, intended for implementation across European centres. However, universally accepted paediatric criteria are needed to ensure prompt diagnosis, definitive treatment, and improved outcomes for children, adolescents, and young adults with sinusoidal obstructive syndrome, and to facilitate international clinical research collaboration. We convened an international panel of multidisciplinary experts including physicians with expertise in HSCT, paediatric intensive care, nephrology, hepatology, radiology, pathology, and transfusion medicine; HSCT advanced-practice providers and medical trainees; pharmacists; and translational and basic science researchers from the Pediatric Acute Lung Injury and Sepsis Investigators Network, the EBMT, the Pediatric Blood and Marrow Transplant Consortia, and several other institutions with extensive experience in sinusoidal obstructive syndrome. Panellists convened at The University of Texas, MD Anderson Cancer Center (Houston, TX, USA) in February, 2019, to evaluate the available evidence. In this expert position statement paper, we provide consensus recommendations for the international implementation of guidelines for the diagnosis, severity grading, and treatment of sinusoidal obstructive syndrome among children, adolescents, and young adults. We endorse universal adoption of paediatric diagnostic guidelines for sinusoidal obstruction syndrome as proposed by the EBMT, and provide implementation guidance for standardisation across centres; we have further proposed adjunctive use of age-appropriate organ-specific toxicity criteria for severity grading and provided prophylaxis and treatment considerations among children and adolescent and young adult patients. Key recommendations include: (1) liver biopsy, portal venous wedge pressure, and reversal of portal venous flow on Doppler ultrasonography should not be used for the routine diagnosis of sinusoidal obstructive syndrome in children, adolescents, and young adults; (2) platelet refractoriness can be defined as a corrected count increment of less than 5000-7500 following at least two sequential ABO-compatible fresh platelet transfusions; (3) hepatomegaly is best defined as an absolute increase of at least 1 cm in liver length at the midclavicular line; and if a baseline measurement is not available, hepatomegaly can be defined as greater than 2 SDs above normal for age; and (4) the presence and volume of ascites can be categorised as mild (minimal fluid by liver, spleen, or pelvis), moderate (<1 cm fluid), or severe (fluid in all three regions with >1 cm fluid in at least two regions).
PICO Summary
Population
Paediatric patients with sinusoidal obstruction syndrome / hepatic veno-occlusive disease
Intervention
Guidelines produced by an international panel of multidisciplinary experts from the Pediatric Acute Lung Injury and Sepsis Investigators Network, the EBMT, the Pediatric Blood and Marrow Transplant Consortia, and several other institutions with extensive experience in sinusoidal obstructive syndrome.
Comparison
None
Outcome
Key recommendations include: (1) liver biopsy, portal venous wedge pressure, and reversal of portal venous flow on Doppler ultrasonography should not be used for the routine diagnosis of sinusoidal obstructive syndrome in children, adolescents, and young adults; (2) platelet refractoriness can be defined as a corrected count increment of less than 5000-7500 following at least two sequential ABO-compatible fresh platelet transfusions; (3) hepatomegaly is best defined as an absolute increase of at least 1 cm in liver length at the midclavicular line; and if a baseline measurement is not available, hepatomegaly can be defined as greater than 2 SDs above normal for age; and (4) the presence and volume of ascites can be categorised as mild (minimal fluid by liver, spleen, or pelvis), moderate (<1 cm fluid), or severe (fluid in all three regions with >1 cm fluid in at least two regions).