Clinical Analysis Of Hepatic Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome After Hematopoietic Stem Cell Transplantation For Thalassemia Major

Objective:Hepatic veno-occlusive disease or sinusoidal obstruction syndrome(VOD/SOS)is a potentially life-threatening complication of allogeneic hematopoietic stem cell transplantation(allo-HSCT).In this clinical study,we aimed to investigate the incidence,management and outcome of VOD/SOS in patients with thalassemia major(TM)who received allo-HSCT.Methods:In this study,clinical analysis was performed on 521 TM patients who underwent HSCT in our hospital from July 2007 to July 2019,including335 males and 186 females,with a median age of 5(2-19)years.There were 394 sibling donor(MSD)transplants,103 unrelated donor(URD)transplants,and 24 haploidentical transplants.Conditioning regimen consisted of Bu,Cy,fludarabine(Flu)and anti-thymocyte globulin(ATG).Gv HD prophylaxis regimen for MSD HSCT consisted of cyclosporine A(Cs A),methotrexate(MTX),and a low-dose,short-course mycophenolate mofetil(MMF).Gv HD prophylaxis regimen for URD HSCT and haploidentical HSCT consisted of tacrolimus,MTX and short-course MMF.Prophylactic regimen for VOD/SOS was a combination of dalteparin and lipo-PGE1.Prophylactic therapy consisting of dalteparin and lipo-PGE1 was given until day 21.Once VOD/SOS was clinically diagnosed,standard supportive care measures were adopted,such as restriction of daily sodium and fluid intake,diuretics,and hematologic support.All patients diagnosed with VOD/SOS were timely administered with dalteparin.CNIs were immediately discontinued for all patients diagnosed with VOD/SOS.The methylprednisolone and anti-CD25 monoclonal antibody(basiliximab)were administered to continue the prophylaxis or therapy of Gv HD.After the clinical symptoms of VOD/SOS were improved,CNIs were resumed to continue the prophylaxis or therapy of Gv HD.Results:1.Among the 521 TM patients,54(10.4%)had postoperative VOD/SOS,with a cumulative incidence of 10.4%(95%CI,8.9-13.4),among which 32(59.3%)had mild VOD/SOS,and 22(40.7%)had moderate VOD/SOS,with a median occurrence time of 12 days(2-28 days).The results of univariate analysis showed that age,gender,ferritin level,liver size,Pesaro grading,donor gender,ABO blood group matching from stem cells,ineffective platelet transfusion in transplantation,occurrence of Gv HD,The incidence of sepsis after transplantation was not significantly correlated with the occurrence of VOD/SOS,but the cumulative incidence of moderate VOD/SOS in MUD group was 8.7%(95%CI,4.7-16.3),which was significantly higher than that in MSD group(3.1%(95%CI,1.8-5.4)(P=0.010).2.The median follow-up time was 38 months(1-150 months),and there was no difference in the incidence of VOD/SOS after transplantation in TM patients and the incidence of OS transplantrelated mortality(TRM)in patients without VOD/SOS.Among the 54 patients,51 survived,with a survival rate of94.4%.No patients progressed to severe VOD/SOS and died from VOD/SOS.3patients(5.6%)died from TRM,including 2 from post-transplant lymphoproliferative disease and 1 from interstitial pneumonia.Conclusion:1.The incidence of VOD/SOS after HSCT in TM patients in our hospital was10.4%,indicating a higher incidence.2.Early diagnosis,reasonable symptomatic treatment and timely short-term withdrawal of CNIs for prevention and treatment of Gv HD can effectively improve VOD/SOS prognosis.