scholarly journals Preliminary Report for the Development of a Multiparameter Protocol for the Identification of Sinusoidal Obstruction Syndrome including Abdominal Ultrasound before and after Allogeneic Stem Cell Transplantation

2022 ◽  
Vol 12 (2) ◽  
pp. 829
Author(s):  
Sebastian Schlaweck ◽  
Claus Juergen Bauer ◽  
Friederike Schmitz ◽  
Peter Brossart ◽  
Tobias A. W. Holderried ◽  
...  

Sinusoidal obstruction syndrome (SOS) is a rare complication after allogeneic hematopoietic stem cell transplantation (alloHSCT) caused by endothelial dysfunction. Previous definitions and diagnostic criteria for the presence of SOS include bilirubinemia, hepatomegaly and weight gain, but histological evaluation is still the only way to prove the diagnosis of SOS. However, biopsy remains an invasive technique and is therefore undesirable in the alloHSCT scenario. Hence, a non-invasive diagnostic strategy is critical. Besides thorough clinical assessment and laboratory values, ultrasound examination remains part of the diagnostic workflow in clinical routine. Previous studies defined sonographic abnormalities, which are associated with the occurrence of SOS, but a standardized protocol to perform reliable abdominal ultrasound has not been finally defined. In this study, we evaluated a multi-parameter protocol including laboratory values as well as ultrasound examination pre- and post-alloHSCT. The application of this protocol was feasible in clinical practice and achieved a high inter- and intra-rater reliability. In our population, no case of SOS was identifiable and, in line with previous studies, no changes known to be associated with SOS were detected by ultrasound examination in our cohort. Additionally, we investigated subgroups of patients partly fulfilling SOS diagnostic criteria analyzing correlations between the fulfilled criteria and aberrances in ultrasound measurements pre- and post-alloHSCT. Although statistical examination may be limited by a small sample size and missing SOS cases, hyperbilirubinemia, thrombocytopenia and weight gain showed only a coincidence with selected, enlarged liver dimensions in few patients. This may underline the fact that hepatomegaly occurs as an unspecific finding after alloHSCT. Our protocol, including the ultrasound examination pre- and post-alloHSCT and laboratory parameters, may help to rule out SOS early, but validation in a greater population and different transplantation centers is required to warrant broader appliance. Nevertheless, we aim to contribute to an elaborate and standardized work-flow in peri-alloHSCT patient care.

Author(s):  
Thomas Luft ◽  
Peter Dreger ◽  
Aleksandar Radujkovic

AbstractAllogeneic hematopoietic stem cell transplantation (alloSCT) carries the promise of cure for many malignant and non-malignant diseases of the lympho-hematopoietic system. Although outcome has improved considerably since the pioneering Seattle achievements more than 5 decades ago, non-relapse mortality (NRM) remains a major burden of alloSCT. There is increasing evidence that endothelial dysfunction is involved in many of the life-threatening complications of alloSCT, such as sinusoidal obstruction syndrome/venoocclusive disease, transplant-associated thrombotic microangiopathy, and refractory acute graft-versus host disease. This review delineates the role of the endothelium in severe complications after alloSCT and describes the current status of search for biomarkers predicting endothelial complications, including markers of endothelial vulnerability and markers of endothelial injury. Finally, implications of our current understanding of transplant-associated endothelial pathology for prevention and management of complications after alloSCT are discussed.


Author(s):  
Drew Provan ◽  
Trevor Baglin ◽  
Inderjeet Dokal ◽  
Johannes de Vos ◽  
Hassan Al-Sader

Haemopoietic stem cell transplantation (SCT) - Indications for haemopoietic SCT - Allogeneic SCT - Autologous STC - Investigations for BMT/PBSCT - Pretransplant investigation of donors - Bone marrow harvesting - Peripheral blood stem cell mobilization and harvesting - Microbiological screening for stem cell cryopreservation - Stem cell transplant conditioning regimens - Infusion of cryopreserved stem cells - Infusion of fresh non-cryopreserved stem cells - Blood product support for SCT - Graft-versus-host disease (GvHD) prophylaxis - Acute GvHD - Chronic GvHD - Veno-occlusive disease (syn. sinusoidal obstruction syndrome) - Invasive fungal infections and antifungal therapy - CMV prophylaxis and treatment - Post-transplant vaccination programme and foreign travel - Longer term effect post-transplant - Treatment of relapse post-allogeneic SCT - Discharge and follow-up


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3886-3886 ◽  
Author(s):  
Bernd Gruhn ◽  
Susan Wittig ◽  
Clemens Arndt ◽  
Claudia Seifert

Abstract Background:Hepatic sinusoidal obstruction syndrome (SOS), commonly known as veno-occlusive disease of the liver is a life-threatening early complication after hematopoietic stem cell transplantation (HSCT). Until now, examinations about the influence of genetic risk factors are extremely rare. Heparanase (HPSE), a pivotal endoglycosidase responsible for heparan sulfate degradation, is expressed by activated endothelial cells. HPSE has been shown to be involved in inflammation and may therefore play an important role in the pathogenesis of hepatic SOS. The purpose of this study was to identify an association between HPSE single nucleotide polymorphisms (SNPs) and hepatic SOS in children undergoing allogeneic HSCT. Methods:160 children (median age, 14 years) who underwent allogeneic bone marrow (n=91) or peripheral blood stem cell transplantation (n= 69) in a single center and their respective donors were genotyped of HPSE for rs4693608 and rs4364254 using TaqMan real-time polymerase chain reaction. The donor was HLA-matched unrelated in 63% of transplants and HLA-identical related in 25% of transplants. Conditioning regimen was myeloablative in all cases and based on busulfan in 46% of transplants or total body irradiation in 33% of transplants. Two forms of post-transplant immunosuppression predominated, cyclosporine A and methotrexate in 50% of transplants and cyclosporine A alone in 30% of transplants. Results:160 donor/patient pairs were analyzed. Cell samples from the patient were available in 155 cases and from the donor in 153 cases. Genotype AG of HPSE rs4693608 SNP was found in 82 patients (53%), AA in 49 patients (32%), and 24 patients were homozygous for GG (15%). Analysis of HPSE rs4364254 SNP revealed a similar distribution for TC (n=69, 44%) and TT (n=68, 44%) and a frequency of 18 patients (12%) for CC. Hepatic SOS was observed in 12 patients (8%). According to the modified Seattle criteria we identified ten patients with early-onset disease in the first 20 days after HSCT and two patients who developed hepatic SOS later on day +44 and day +83 after transplantation (late-onset SOS), respectively. If hepatic SOS was diagnosed all of our patients were treated with defibrotide as early as possible. Two patients (17%) developed severe hepatic SOS and died of multi-organ failure. The remaining ten patients with hepatic SOS (83%) could be successfully treated and survived. Patients with HPSE genotypes GG or AG of rs4693608 (G>A) had a significantly reduced incidence of hepatic SOS on day 100 after HSCT compared to patients with genotype AA (5% vs. 14%, p=0.038). In addition, incidence of hepatic SOS in patients with genotype CC or CT of rs4364254 (C>T) was significantly decreased in comparison to patients with genotype TT (2% vs. 15%, p=0.004). Interestingly, no patient with genotype CC developed hepatic SOS. Because both SNPs co-occur in vivo, we generated subsets: AA-TT, GG-CC and a group with remaining SNP combinations. We found significant differences between all three patient groups (p=0.035). Patients with AA-TT showed the highest incidence of hepatic SOS (17%), while hepatic SOS was not observed in patients with GG-CC (0%) and residual combinations were numerically in-between (5%). An impact caused by main patient and donor characteristics, established risk factors for hepatic SOS, and conditioning regimen could be excluded in multivariate analyses. Conclusions: This study provides the first evidence that HPSE polymorphisms are significant independent risk factors (p=0.030) for the development of hepatic SOS and should be evaluated in further trials. Disclosures No relevant conflicts of interest to declare.


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