Diagnosis Of Sinusoidal Obstruction Syndrome Research Articles

Evaluation of Endothelial Damage in Sinusoidal Obstructive Syndrome

Introduction: Sinusoidal Obstructive Syndrome (SOS) is a complication derived from the endothelial damage associated to hematopoietic stem-cell transplant (HSCT) conditioning. Although its appearance is highly dependent on patient risk factors, it has an estimated prevalence of 14% and is associated with a high morbidity and with mortality rates than can ascend to 90% at day +100 of transplant in severe cases. New methods to early diagnose SOS are needed in order to minimize the incidence and severity of SOS.Here we present preliminary results of our single center prospective study that aims to measure and validate a panel of biomarkers in plasma [L-Ficolin, hyaluronic acid (HA), vascular adhesion molecule-1 (VCAM1) and plasminogen activator inhibitor-1 (PAI-1)] which have been recently described to be prognostic of the development of SOS (Akil et al, Biol. Blood Marrow Transplant. 21, 1739-1745, 2015).Methods: Twenty-one adult patients undergoing HSCT were recruited (median age 43.5 years old, 20-68), 15 men and 6 women. Three patients (14%) were diagnosed of SOS and received defibrotide (Gentium/Jazz Pharmaceutical) treatment. Diagnosis of SOS was performed based on the Seattle and Baltimore modified Criteria.Citrated blood samples from all patients were obtained before starting conditioning regimen (V0), and at infusion day (V1), 7 (V2) and 14 (V3) after infusion. Three additional samples (V4, V5 and V6) were drawn from those patients with SOS (just before defibrotide and 7 and 14 days after treatment with defibrotide). Samples were centrifuged twice at 23°C (15 min at 1,500 g, and 2 min at 13,000 g) and aliquots were stored at -80ºC until analysis.Phosphatidylserine-MP (Ph-MP) and tissue factor-MP (TF-MP) dependent procoagulant activities were determined with the ZYMUPHEN kits. VCAM1, PAI-1, L-Ficolin and HA concentrations were measured by ELISA.Data from the routine laboratory analysis were also registered.Statistical analyses was performed with SPSS software. Values of p≤0.05 were considered statistically significant.Results : Considering transplant type, 9 were autologous and 9 allogenic in controls, and 3 allogenic in SOS; donor type were 3 unrelated, 6 related and 3 haploidentical in controls, and 3 related and 2 haploidentical in SOS. Conditioning regimen intensity was 7 full, 2 reduced, 8 with busulfan and 1 with total body irradiation in controls and 3 reduced and 2 with busulfan in SOS group. Controls received 2(1-4) previous chemotherapy lines whereas SOS group received 3(2-9).Regarding diseases, 4 presented acute myeloblastic leukemia, 2 acute lymphoblastic leukemia, 3 multiple myeloma, 3 non-Hodgkin's lymphoma and 6 Hodgkin's disease in control group whereas in SOS group 1 had acute myeloblastic leukemia, 1 myelodysplastic syndrome and 1 non-Hodgkin's lymphoma.As observed, occurrence of SOS did not seem to be related to either the malignant disease or number of chemotherapy drugs employed for its treatment or donor type and conditioning regimen.L-Ficolin, a complement activator involved in homeostatic clearance of mitochondria in the liver, seemed to diminished in the SOS group at V3 (wo SOS : 1025±923 ng/mL ; SOS : 680±817 ng/mL). Nevertheless, this diminution was not significant probably due to the few patients with SOS.No differences were observed between patients without and with SOS in plasma levels of markers of endothelial damage VCAM1, PAI-1 and HA, this last a direct indicator of hepatic sinusoidal endothelial cell function.Procoagulant activity associated to Ph-MP was lower in patients with SOS (p=0.023) whereas that associated to TF-MP was unaffected.Plasma levels of VCAM1 and HA increased along time in both groups. After treatment with defibrotide these values achieved steady levels in SOS patients (V4 and V5). On the other hand, PAI-1 did not change over time.SOS patients presented at V3 higher total bilirrubin (wo SOS: 0.86±0.53 mg/dL; SOS: 2.31±0.18 mg/dL, p=0.008) and lower albumin levels (wo SOS: 3.5±0.3 g/dL; SOS: 2.7±0.1 g/dL)Conclusions: Our results indicate that endothelial damage is present in all patients undergoing HSCT and that treatment of SOS patients with defibrotide might restrain this injury. Due to the low number of patients included so far, we cannot conclude anything about the value of biomarkers proposed to serve as predictors of SOS onset. Our study is still open and recruiting patients.This work was supported by Jazz Pharmaceutical DisclosuresNo relevant conflicts of interest to declare.

Increased hepatic FDG uptake on PET/CT in hepatic sinusoidal obstructive syndrome.

PurposeImaging features of sinusoidal obstruction syndrome (SOS), an increasingly common drawback of chemotherapy, were evaluated via 18F-fluorodeoxyglucose (FDG) positron emission tomography computed tomography (PET/CT).Experimental DesignThis retrospective study was approved by our Institutional Review Board, with a waiver of informed consent. FDG PET/CT studies of 35 patients (male, 24; female, 11; median age, 53.2 years) obtained between January, 2005 and December, 2012 were analyzed before and after systemic chemotherapy. Diagnosis of SOS was based on histologic (n=13) or gadoxetic acid-enhanced MRI (n=22) findings. On PET/CT images, ROIs drawn on non-tumorous liver generated mean standardized uptake value (SUVliver). Total lesion glycolysis of liver (TLGliver) was calculated as: SUVliver × CT-derived hepatic volume. Paired t-test was applied to compare changes before and after SOS.ResultsMean (±standard error [SE]) values of hepatic volume (baseline, 1307.7±46.2 cm3; SOS, 1395.4±41.3 cm3; p=0.004), SUVliver (baseline, 2.08±0.06; SOS, 2.27±0.07; p=0.02), and TLGliver (baseline, 2697.5±114.5; SOS, 3170.2±134.2; p=0.001) significantly increased with development of SOS. In contrast, mean SUVaorta was unchanged (baseline, 1.53±0.04; SOS, 1.50±0.04; p=0.52).ConclusionsHepatic FDG uptake on PET/CT intensified after onset of SOS and thus may be an inappropriate reference in this setting, potentially skewing chemotherapeutic responses gauged by lesion-to-liver SUV ratio.

Preoperative assessment of chemotherapeutic associated liver injury based on indocyanine green retention test

BackgroundThe aim of the study was to assess the capacity of indocyanine green retention test at 15 min (ICGR15) to predict chemotherapeutic-associated liver injuries (CALI). MethodsPatients undergoing liver resection for CLM that received preoperative oxaliplatin and/or irintecan-based chemotherapy within 3 months before surgery and scheduled first hepatectomy were considered. Results166 out of 983 patients treated between 01/2001 and 04/2014 fulfilled the inclusion criteria. The median number of cycles of preoperative chemotherapy was 6.0 ± 4.87. Chemotherapy was mainly based on oxaliplatin in 123 (74.1%). Bevacizumab was associated in 51(31%) patients. A total of 102 (61.4%) patients had at least 1 CALI. Grade 2–3 steatosis occurred in 56 (33.7%) patients and steatohepatitis in19(11.5%). Sinusoidal obstructive syndrome (SOS) was presented in 93 (56%) patients. 23(13.8%) patients had nodular regeneration hyperplasia. At multivariate analysis the only predictive factor of ICGR≥10% was age≥65 years (p = 0.001). A median split (ICGR15 = 8%) was used to categorized ICGR15 value. Multivariate analysis showed that age≥ 65 [OR 2.530 (CI95% 1.28–4.97) p < 0.001], male sex [OR 2.614 (CI95% 1.31–5.20) p < 0.001], SOS [OR 1.954 (CI95% 1.00–3.81) p = 0.050] and administration of Bevacizumab [OR 2.201 (CI95% 1.07–4.50) p = 0.031] were predictive factors for ICGR≥8%. ConclusionsICGR15 test can predict the diagnosis of SOS. High ICGR15 value is more common in elderly male patients and after bevacizumab administration.

Biomarkers for Diagnosis and Prognosis of Sinusoidal Obstruction Syndrome after Hematopoietic Cell Transplantation

Reliable, noninvasive methods for diagnosing and prognosing sinusoidal obstruction syndrome (SOS) early after hematopoietic cell transplantation (HCT) are needed. We used a quantitative mass spectrometry–based proteomics approach to identify candidate biomarkers of SOS by comparing plasma pooled from 20 patients with and 20 patients without SOS. Of 494 proteins quantified, we selected 6 proteins (L-Ficolin, vascular cell adhesion molecule-1 [VCAM1], tissue inhibitor of metalloproteinase-1, von Willebrand factor, intercellular adhesion molecule-1, and CD97) based on a differential heavy/light isotope ratio of at least 2 fold, information from the literature, and immunoassay availability. Next, we evaluated the diagnostic potential of these 6 proteins and 5 selected from the literature (suppression of tumorigenicity-2 [ST2], angiopoietin-2 (ANG2), hyaluronic acid [HA], thrombomodulin, and plasminogen activator inhibitor-1) in samples from 80 patients. The results demonstrate that together ST2, ANG2, L-Ficolin, HA, and VCAM1 compose a biomarker panel for diagnosis of SOS. L-Ficolin, HA, and VCAM1 also stratified patients at risk for SOS as early as the day of HCT. Prognostic Bayesian modeling for SOS onset based on L-Ficolin, HA, and VCAM1 levels on the day of HCT and clinical characteristics showed >80% correct prognosis of SOS onset. These biomarkers may provide opportunities for preemptive intervention to minimize SOS incidence and/or severity.

Cyclophosphamide Followed By Busulphan in Place of Standard BuCy Regimen for Patients Undergoing Allogeneic Stem Cell Transplantation: A Preliminary Experience from a Single Centre in India

Cyclophosphamide Followed By Busulphan in Place of Standard BuCy Regimen for Patients Undergoing Allogeneic Stem Cell Transplantation: A Preliminary Experience from a Single Centre in India

Biomarkers for hepatic sinusoidal obstruction syndrome after hematopoietic cell transplantation.

Biomarkers for hepatic sinusoidal obstruction syndrome after hematopoietic cell transplantation.

Biomarkers for Diagnosis and Prognosis of Sinusoidal Obstruction Syndrome after Hematopoietic Stem Cell Transplantation

Background. Sinusoidal obstructive syndrome (SOS) is a life-threatening liver injury complication that affects up to 20% of patients receiving allogeneic HSCT in some centers. Symptoms may be variable in less severe cases and the etiology of abdominal pain, weight gain, and elevated bilirubin following HSCT presents a diagnostic challenge. Although a few potential biomarkers for SOS have been identified based on hypothesis-driven testing, there is still no validated blood test for SOS.Methods. We used a mass spectrometry-based proteomics discovery approach comparing plasma pooled from 19 patients with SOS to plasma pooled from 19 patients without SOS. Of 494 proteins quantified, 151 proteins showed at least 2-fold increase in the heavy/light isotope ratio, and 77 proteins showed a ratio of 0.5 or less. We selected 6 proteins [L-Ficolin, vascular cell adhesion molecule-1 (VCAM1), tissue inhibitor of metalloproteinase-1, von-Willebrand factor, intercellular adhesion molecule-1, and CD97] based on their ratio, their involvement in relevant pathway networks, and other information from published literature, and the availability of a sandwich ELISA. In addition, five endothelial markers [suppressor of tumorigenicity 2 (ST2), angiopoietin2 (ANG2), hyaluronic acid (HA), thrombomodulin (sCD141), and plasminogen activator inhibitor-1 (PAI-1)] were measured based on previous demonstrations of their involvement in SOS or in refractory GVHD.Using sequential ELISA, levels of these 11 proteins were measured in plasma from a validation set of 45 patients: 32 SOS patients at disease onset (days +14 to +21 post-HSCT) and from 13 time-matched controls. We tested the value of these proteins as diagnostic biomarkers of SOS using two-sample t-tests and by calculating the area under the receiver operating characteristic curve (AUC of the ROC). Next, we tested the prognostic significance of these biomarkers using Wilcoxon Rank-Sum analysis of their levels measured prior to the clinical signs (days 0 and +7 post-HSCT). We also examined these markers in an independent set of 35 patients (13 SOS+; 22 SOS-). Finally, a Naïve Bayes classifier implemented in Waikato Environment for Knowledge Analysis (WEKA) was developed for SOS prognosis based on a balanced subset of 24 patients (11 SOS-; 13 SOS+). The classifier performance was evaluated by doing a 10-fold cross-validation.Results. Of the 11 proteins tested, 8 were diagnostic markers of SOS with p-values<0.001 and with AUC between 0.91 and 0.70 (Figure 1A). Of note, PAI-1 which was previously identified and which was considered as the gold standard marker for SOS had an AUC of only 0.68 as compared to the five best diagnostic markers. Together ST2, ANG2, L-Ficolin, HA, and VCAM1 compose a biomarker panel for diagnosis of SOS with an AUC of 0.98 (Figure 1B). We next evaluated the prognostic value of these biomarkers in samples collected prior to the clinical signs of SOS. L-Ficolin (Figure 1C), HA, and VCAM1 can stratify patients at risk of SOS as early as the day of HSCT (AUC = 0.83 to 0.69) and were also validated as diagnostic and prognostic markers of SOS in the independent set of 35 patients despite the smaller sample size (not shown). The Naïve Bayes classifier for SOS prognosis was developed using nine clinical attributes (e.g. age, gender, donor type) and day zero post-transplant levels of VCAM-1, L-Ficolin and HA. 83.33% of patients were correctly classified (ROC area of 0.902). Of the misclassified patients (16.67%), 25% were false positive and 75% were false negative. Classifying patients based on solely clinical attributes only resulted in 58.33% correct classification (ROC area of 0.608) indicating minimal to no prediction.Conclusions. Together ST2, ANG2, L-Ficolin, HA, and VCAM1 represent a biomarker panel for reliable, non-invasive diagnosis of SOS (composite AUC = 0.98). Furthermore, L-Ficolin, HA, and VCAM1 are prognostic biomarkers of SOS before the appearance of clinical symptoms. The identified markers represent several pathways, including previously suspected pathways involved in hemostasis and endothelial injury as well as novel pathways related to innate immunity and homeostatic clearance of mitochondria. Once further validated, these biomarkers could provide opportunities for preemptive intervention to minimize the incidence and severity of SOS clinical symptoms, and thereby increase survival. [Display omitted] DisclosuresCarreras:Gentium/Jazz : Grant from Gentium/Jazz to study the MoA of Defibrotide Other.

Cyclophosphamide Followed By Busulphan in Place of Standard BuCy Regimen for Patients Undergoing Allogeneic Stem Cell Transplantation: A Preliminary Experience from a Single Centre in India

▪Conditioning regimens are an important issue determining the outcome of hematopoietic stem cell transplantation (HSCT). Altering the administration order of Busulphan (Bu) and Cyclophosphamide (Cy) during conditioning from conventional method of administering Bu followed by Cy had resulted in an improved toxicity profile in few animal and subsequent human studies. However the data substantiating this approach is limited.We retrospectively analyzed all consecutive patients receiving allogeneic stem cell transplant (Allo SCT) with myeloablative conditioning from 2009 to 2013. A total of 40 patient received Allo SCT of which 18 patient received Bu-Cy and 22 patients received Cy-Bu conditioning regimen. The Bu–Cy conditioning regimen consisted of i.v. Bu 0.8 mg/kg administered every 6 h (16 doses) on days −7 to −4, followed by i.v. Cy 60 mg/kg on days −3 and −2. Patients with the Cy–Bu regimen received i.v. Cy 60 mg/kg on days −7 and −6; followed by i.v. Bu 0.8 mg/kg administered every 6 hr (16 doses) on days −5 to −2. GVHD prophylaxis was given with Cyclosporine A and methotrexate. Common Terminology Criteria for Adverse Events version 3.0 (CTCAE) was used for assessment of toxicity. The diagnosis of sinusoidal obstruction syndrome (SOS) was based on modified Seattle criteria.Pre-transplant characteristics were comparable in the two cohorts (Table 1a and 1b). Time to platelet engraftment was earlier in the Cy-Bu cohort (21 days vs. 16 days; P=0.008) (Table 2).Treatment related side effects were similar in both the groups except hepatotoxicity which was higher in Bu-Cy as compared to Cy-Bu group (10 (55.16%) vs. 3 (13.64%); p=0.03). There was no significant difference in treatment related mortality (TRM) at day 100; however there was trend towards higher TRM at day 30 in Bu-Cy group (3 vs. none; p=0.083).There was no difference in aGVHD incidence, grade or stage of organ involved between the 2 groups.As in previous studies hepatotoxicity in the present analysis was found to be less in patients who received Cy-Bu as the conditioning regimen and there was earlier platelet engraftment in this group. These findings suggest Cy-Bu has better toxicity profile than conventional Bu-Cy regimen. However further prospective studies are required to confirm these findings.Table 1aBaseline CharacteristicsPatient Characteristics Bu-Cy (n=18)Cy-Bu (n=22)P valueSexMale15160.424Age (in yrs)Median (Range)17 (1-50)16 (1-48)≤18913≥1899Underlying DiseaseAML14120.415ALL34CML13MDS02Primary Myelofibrosis01Pre-transplant Remission StatusCR11110.482Performance status (ECOG)0430.3141916HSCT Comorbidity Index014150.341115222310Table1bBaseline CharacteristicsTransplant characteristicsBu-CyCy-BuP valueTime from diagnosis to TransplantMean (days) + SD548.16750.567HLA MatchingHLA identical (6/6)17210.884HLA mismatch (5/6)11DonorMatched Sibling17160.884UCB11Donor AgeMedian(Range)20 (0-47)16 (0-50)0.781Donor SexMale5140.034Female128Sex mismatch12130.458Female Donor in Male patient1170.064Harvest SourcePeripheral Blood (PB)15210.269Bone Marrow (BM)20Cord Blood (UCB)11CD 34 Count(x106 cells/kg)Mean+SD5.12+2.605.66+2.370.499CD 3 Count(x107 cells/kg)Mean25.517.50.200Table 2ResultsOutcomeBu-CyCy-BuPANC recovery14 (11-30)11 (8-32)0.119Platelet recovery21 (17-44)16 (11-27)0.008Platelets transfused6 (1-10)4 (1-15)0.166Days of GCSF18 (12-36)14 (9-37)0.126D100 Complete Donor Chimerism9 (90%)12(85.71%)1.000Transplant Response15/17 (88.24%)19/22 (86.36%)1.000 Days of Antimicrobial use13 (0-34)13 (0-36)0.83 Hepatotoxicity (grade3-4)10/18 (55.56%)3/22 (13.64%)0.030Nephrotoxicity (grade3-4)3/18 (16.67%)1/22 (4.55%)0.204Mucositis (grade3-4)6/18 (33.33%)6/22 (27.27%)0.677Any Grade 3-4 toxicity10/18 (55.56%)9/22 (40.91%)0.356D30 TRM3 (16.67%)00.083D100 TRM4 (22.22%)2 (10%)0.395Follow up28.67 months7.6 monthsAcute GVHD3/18 (16.67%)5/22 (22.73%)0.709 DisclosuresNo relevant conflicts of interest to declare.

Diagnosis of sinusoidal obstruction syndrome by positron emission tomography/computed tomography: Report of two cases treated by defibrotide

Sinusoidal obstruction syndrome (SOS) is a potentially fatal liver injury that mainly occurs after myeloablative chemotherapy. We report two cases of SOS investigated by 18F-fluorodeoxyglucose positron emission tomography/computed tomography and treated with defibrotide.

Allogeneic hematopoietic SCT for adults AML using i.v. BU in the conditioning regimen: outcomes and risk factors for the occurrence of hepatic sinusoidal obstructive syndrome

I.v. BU is frequently used in the conditioning regimen prior to allogeneic hematopoietic SCT (allo-HSCT); however, overall outcomes, incidence of hepatic sinusoidal obstructive syndrome (SOS) and its risk factors are not well known. With this aim, we performed a study on 257 AML adult recipients. Seattle Criteria were used for diagnosis and classification of SOS. The median age was 44 years. Donors were HLA-identical siblings in 60%, HLA-matched unrelated in 29% and HLA mismatched in 11%. Conditioning regimen was myeloablative in 84% (i.v. BU with CY was the most frequently used regimen) and it was reduced intensity in 16% (i.v. BU associated with fludarabine). Acute and chronic GVHD was observed in 28% and 44%, respectively. Two-year incidence of non-relapse mortality was 16±2% and 2-year leukemia-free survival for patients in CR1, CR2 and non remission at HSCT were 55±4%, 58±7%, and 20±5%, respectively. At 6 months, incidence of SOS was 7.8±2%; and it was severe in eight patients (3%). Factors associated with the occurrence of SOS were: HLA-mismatched donor HSCT (P=0.002) and patients transplanted in non-remission (P=0.002). In conclusion, outcomes of HSCT using i.v. BU are encouraging in this setting, SOS incidence is low and it is influenced by the type of donor and disease status at the time of transplant.

Tolvaptan as an alternative treatment for refractory fluid retention associated with sinusoidal obstruction syndrome after allogeneic stem cell transplantation

Tolvaptan is an oral vasopressin V2-receptor antagonist recognized as effective for fluid retention associated with congestive heart failure and liver cirrhosis. However, there have been no reports concerning clinical experience with tolvaptan for sinusoidal obstruction syndrome (SOS). A 42-year-old male with primarily refractory T-lymphoblastic lymphoma underwent allogeneic peripheral blood stem cell transplantation from an HLA-matched sibling donor. The myeloablative conditioning regimen consisted of busulfan and cyclophosphamide. On day 20, the total bilirubin level was elevated to 2.0 mg/dL, and body weight increased from 76 to 85 kg, allowing a diagnosis of SOS to be made. Treatments with thrombomodulin, furosemide, carperitide, and low-dose dopamine were ineffective. By day 27, the patient's body weight had increased to 90 kg, and he subsequently developed cardiopulmonary failure. Therefore, we administered low-dose tolvaptan for 2 days (3.75 mg on day 27 and 7.5 mg on day 28). Consequently, his ascites and edema were significantly reduced, and body weight returned to 77 kg by day 34. However, he died of lymphoma progression on day 55. Tolvaptan may be an alternative and promising treatment for refractory fluid retention associated with SOS, although it is unclear whether tolvaptan administration leads to improvement in clinical outcome.

Accuracy of gadoxetic acid-enhanced magnetic resonance imaging for the diagnosis of sinusoidal obstruction syndrome in patients with chemotherapy-treated colorectal liver metastases

To assess whether reticular hypointensity on hepatobiliary phase images of gadoxetic acid-enhanced magnetic resonance imaging (EOB-MRI) is a diagnostic finding of sinusoidal obstruction syndrome (SOS) in patients with hepatic metastases who have undergone chemotherapy. We retrospectively analysed EOB-MRI of 42 patients who had undergone chemotherapy before hepatic resection of colorectal hepatic metastases. Two radiologists, who were unaware of whether or not the patients had SOS, reviewed the hepatobiliary phase images to determine the presence of hypointense reticulation in the liver using a 5-point scale. The sensitivity, specificity and area under the receiver operating characteristics curve (A(z)) were calculated for each reviewer. The sensitivity, specificity and A(z) for the diagnosis of SOS were 75%, 100% and 0.957 for reader 1 and 75%, 96.2% and 0.936 for reader 2, respectively. In one patient who received a false-positive diagnosis by one reader, there was sinusoidal fibrosis on histological examination, but not diagnostic for SOS. False-negative diagnosis occurred in four patients for both readers; histology of these patients showed minimal and localised sinusoidal congestion and fibrosis. Reticular hypointensity on hepatobiliary phase images of EOB-MRI is highly specific for the diagnosis of SOS in patients with treated colorectal hepatic metastases. Gadoxetic acid enhanced magnetic resonance imaging (EOB-MRI) can identify the sinusoidal obstruction syndrome (SOS). The diagnosis can be achieved with high specificity and good interobserver agreement. SOS typically demonstrates diffuse hypointensity on hepatobiliary phase images on EOB-MRI. EOB-MRI may be falsely negative in patients with minimal degree of SOS.

Serum ferritin as risk factor for sinusoidal obstruction syndrome of the liver in patients undergoing hematopoietic stem cell transplantation

AbstractHepatic sinusoidal obstruction syndrome (SOS) is a serious complication in hematopoietic stem cell transplant (HSCT) recipients. To determine the impact of pretransplantation hyperferritinemia on the risk of SOS after HSC transplantation, we retrospectively studied 427 HSCT recipients (179 autologous and 248 allogeneic). Serum ferritin levels were measured before transplantation. Patients with and without a diagnosis of SOS were compared regarding demographics; underlying disease; transplant characteristics; receipt of imatinib, busulfan, total body irradiation, gemtuzumab, vancomycin, acyclovir, or methotrexate; and baseline serum ferritin. Univariate and multivariate (stepwise logistic regression) analyses were performed. SOS was diagnosed in 88 patients (21%) at a median of 10 days (range, 2-29 days) after transplantation. By multivariate analysis, allogeneic HSC transplantation (odds ratio [OR] = 8.25; 95% confidence interval [95% CI], 3.31-20.57), receipt of imatinib (OR = 2.60; 95% CI, 1.16-5.84), receipt of busulfan (OR = 2.18; 95% CI, 1.25-3.80), and ferritin serum level higher than 1000 ng/dL (OR = 1.78; 95% CI, 1.02-3.08) were risk factors for SOS. A ferritin serum level higher than 1000 ng/dL in the pretransplantation period is an independent risk factor for SOS. The results suggest the need for prospective studies addressing the use of iron chelation in the pretransplantation period.

When should liver biopsy be performed after hematopoietic stem cell transplantation?

When should liver biopsy be performed after hematopoietic stem cell transplantation?

Treatment of Sinusoidal Obstruction Syndrome With Defibrotide: A Single-Center Experience

Sinusoidal obstruction syndrome (SOS) is a frequent, troubling, and potentially fatal complication of hematopoietic stem cell transplantation. Despite promising results with defibrotide (DF), no treatment has been established as standard. DF is a single-stranded polydeoxyribonucleotide, obtained from controlled depolymerization of porcine intestinal mucosal cells. It has antithrombotic, antiischemic, antiinflammatory, and thrombolytic properties without significant side effects. We retrospectively evaluated the charts of 80 consecutive patients, with 89 hematopoietic stem cell transplants for hematologic malignancies. The results of early initiation of DF treatment in 14 patients with SOS are presented in this study. Fourteen patients, 8 males and 6 females % median age 40.5 years (range, 16–46 years) were diagnosed to have SOS. Disease severity was classified as severe in 6 (42.85%), moderate in 4 (28.57%), and mild in 4 (28.57%) patients. We treated 14 patients with DF for a median of 21.5 days (range, 4–39 days). All 14 patients received DF after the diagnosis of SOS. Three patients with severe and all of the patients with mild to moderate SOS responded to treatment with complete resolution of SOS-related signs and symptoms. All patients responding to DF were alive at 100 days posttransplantation. There was no significant drug-related side effect among patients treated with DF. With an overall response rate of 78.56% and a 50% complete response rate in severe SOS cases and minimal side effects, we suggest that DF is the best available agent to treat SOS.