The Clinical Study Of Bleeding And Thrombosis Complications On The Early Phase Of Hematopoietic Stem Cell Transplantation

Objective: (1)To analyze the relevant risk factors and ccurrence of bleeding and thrombosis complications on the early phase of hematopoietic stem cell transplantation (HSCT), and their influences on the survival time of patients following HSCT.Methods: (1)Patient characteristics: From April 2004 to December 2010, 391 patients undergoing HSCT were enrolled in this study. There were 231 males and 160 females, aged from 11 to 64 years(median age was 35 years). The diagnosis were acute myeloid leukemia (AML) in 137 cases, chronic myelogenous leukemia (CML) in 80 cases, acute lymphoid leukemia (ALL) in 71 cases, acute heterozygous leukemia (AHL) in 7 cases , non hodgkin lymphoma (NHL) in 37 cases, hodgkin lymphoma (HL) in 6 cases, multiple myeloma (MM) in 16 cases, myelodysplastic syndrome (MDS) in 14 cases, aplastic anemia (AA) in 11 cases, other diseases in 12 cases. 93 patients received autologous transplantation, and 187 patients received transplants from match sibling donors, 72 from unrelated donors, 31 from partially matched family donors. 8 from umbilical cord blood stem cells transplantation. The condition regimen included modified BU/CY, TBI plus CY, BEAM and some others, according to the type of the donor and disease.(2) All analyses were carried out using SAS version 8.1, using analysis of Logistic regression models to analyse the correlation between factors which are age, sex, the type of transplantation, platelet count, acute graft-versus-host disease (aGVHD), infection, the number of bleeding site, BKV viruria and CMV antigenemia and acute bleeding(including hemorrhagic cystitis) , hemorrhagic cystitis(HC)and thrombosis complications on the early phase of HSCT. Using analysis of Cox's proportional hazard regression model to analyse the correlation between factors which are acute bleeding, thrombosis and death risk. Rate comparison chooses a chi-square test method.Results: (1)Thrombosis occurrence : Thrombosis occurred in 12 of the 391 patients undergoing transplantation (3.1% of all patients), 9 cases were hepatic veno-occlusive disease (HVOD) (2.3%), 1 case were thrombotic microangiopathy (TMA) (0.26%) , 1 case were pulmonary embolism (PE) (0.26%), 1 case were deep venous thrombosis (DVT) (0.26%). The base of diagnosis: AML in 6 cases [not remission (NR) in 3 cases, complete remission-2 (CR2) in 2 cases, CR1 in 1 case], CML-CP in 2 cases, non-hodgkin's lymphoma leukemia in 1 case, HL in 2 cases, AA in 1 case. 9 cases died, death rate is 75%.There are 11 patients suffered from thrombosis in allogeneic HSCT (allo-HSCT), 3.69% of allo-HSCT, 1 patient in autologous HSCT (auto-HSCT), 1.07% of auto-HSCT. Statistic analysis shows no significant difference of the incidence of thrombosis in the two groups(P>0.05), but there are increasing trend of the incidence of thrombosis in allo-HSCT group compare to auto-HSCT group. There are 5 patients suffered from thrombosis complications in aGVHD group (121 cases) (4.1% of aGVHD group); 7 patients in no aGVHD group (270 cases) (2.6% of no aGVHD group); Statistic analysis shows no significant difference of the incidence of thrombosis in the two groups(P>0.05), but there are increasing trend of the incidence of thrombosis in aGVHD group compare to no aGVHD group. There are 8 patients suffered from thrombosis complications in infection group (257 cases) (3.1% of infection group), 4 patients in no infection group (134 cases) ( 2.9% of no infection group). Statistic analysis shows no significant difference of the incidence of thrombosis in the two groups.The incidence of thrombosis in group of conditioning regimen with CD33 monoclonal antibody were 75%, in group of conditioning regimen without CD33 monoclonal antibody were 2.1%,Chi-square statistic analysis shows significant difference of the incidence of thrombosis in two groups (x2=77.0225, P <0.0001). The incidence of thrombosis in group of conditioning regimen with TBI were 8% , in group of conditioning regimen without TBI were 2.1%, Chi-square statistic analysis shows significant difference of the incidence of thrombosis in two groups (x2=5.6409, P=0.0175).(2) Bleeding occurrence: Bleeding events occurred in 310 of the 391 patients undergoing transplantation (79.3% of all patients),it can divided into minor, moderate, severe according to the bleeding indexing standards. 184 cases were minor bleeding (47.1%), 113 cases were moderate bleeding (28.9%), 13 cases were severe bleeding (3.3%). HC occurred in 152 of the 391 patients undergoing transplantation (38.9%), it can divided into grade 1, 2, 3, 4 according to the HC indexing standards, grade 1 in 115 cases (29.4%), grade 2 in 20 cases (5.1%), grade 3 in 13 cases (3.3%), grade 4 in 4 cases (1.1%). The outcome of analyses isⅡ～Ⅳ°GVHD, thrombocytopenia, allo-HSCT, female are bleeding risk factors,the number of bleeding site is the risk of bleeding again (see table 7), more than or equal to 2 bleeding sites is the risk of severe bleeding.Risk factors of bleeding: Platelet is protection factor to prevent bleeding occurred (P<0.0001, OR=0.712, 95%CI: 0.656～0.773), With the reduce of every 5×109 / L the minimum value of platelet count, the risk of bleeding rises (OR=5.457). The risk of bleeding in the group of minimum platelet count less than 15×109/L is higher than the control group (P=0.0279, OR=2.001, 95%CI: 1.078~3.714). The risk of bleeding inⅡ～Ⅳ°aGVHD group is more than in 0～Ⅰ°aGVHD group (P=0.0030, OR=2.391, 95%CI:1.343～4.254). The risk of bleeding in allo-HSCT group is more than in auto-HSCT group (P<0.0109, OR=1.715, 95%CI:1.132～2.598). The number of bleeding site is the risk of bleeding again (P<0.0001, OR=2.100, 95%CI: 1.647～2.678). With the increase of every 2 bleeding sites, the risk of bleeding rises (OR=4.409). More than or equal to 2 bleeding sites is the risk of severe bleeding (P=0.0118, OR=5.356,95%CI:1.450~19.787). The risk of bleeding in female patient is more than in male patient (P=0.0161, OR=1.698, 95%CI: 1.103～2.612).Age is protection factor to prevent bleeding (P<0.0001, OR=0.928, 95%CI: 0.907～0.949), With the increase of every 10 age, the risk of bleeding reduce(OR=0.472). The research results show there are no correlation between infection and bleeding(P>0.05).Risk factors of HC: The statistic analyses shows that CMV antigenemia , BK viruria, the number of bleeding site,Ⅱ～Ⅳ°aGVHD are HC's risk factors(see table 8).The risk of HC in HSCT patients with CMV antigenemia is more than in HSCT patients without CMV antigenemia (P<0.0001, OR=8.495, 95%CI:3.855～18.719), The risk of HC in HSCT patients with BK viruria is more than in HSCT patients without BK viruria (P<0.0001, OR=2.468, 95%CI: 1.856～3.282). The number of bleeding site is the risk of HC (P=0.0092, OR=2.935, 95%CI: 1.305～6.601). With the increase of every 2 bleeding sites, the risk of HC rises (OR=6.093). The risk of HC inⅡ～Ⅳ°aGVHD group is more than in 0～Ⅰ°aGVHD group (P=0.0065, OR=2.193, 95%CI: 1.246～3.860). There are no correlation between age, sex, platelet count, the type of transplantation and HC in this analysis (P>0.05). (3) Survival Analysis: Single factor COX model analysis indicates that thrombosis complications may increase HSCT patients'death risk (P=0.0077, RR=3.407, 95%CI: 1.382～8.398). Analysis shows no relevance between different degree of bleeding and HC and HSCT's 5-year survival rate (P>0.05).Conclusions: (1)Ⅱ～Ⅳ°aGVHD, thrombocytopenia, allo-HSCT and female are the risk of bleeding, the number of bleeding site is the risk of bleeding again, more than or equal to 2 bleeding sites is the risk of severe bleeding.(2) CMV antigenemia, BKV viruria, the number of bleeding site,Ⅱ～Ⅳ°aGVHD are the risk of HC .(3) Thrombosis complications may increase HSCT patients'death risk. Analysis shows no relevance between different degree of bleeding and HC and HSCT's prognosis.