efficacy of basiliximab in the prevention of acute graft-versus-host disease in unrelated allogeneic hematopoietic stem cell transplantation therapy for thalassemia major

Conditions: Beta-Thalassemia Major; Graft-versus-host Disease (GVHD)

Summary: the purpose of this study is to evaluate the basiliximab for prevention of graft-versus-host disease in unrelated allo-genetic hematopoietic stem cell transplantation for thalassemia major. the objective was to evaluate the effect and safety of basiliximab for acute graft-versus-host disease.

allo-geneic stem cell transplantation(allo-hsct) cure thalassemia major by destroying the original hematopoietic and immune systems with a large dose of chemotherapy, rebuilding a new system to correct the abnormal hematopoietic globin chain synthesis which leads to hemolysis. currently, it is the only curative means. according to donors, allo-hsct could be sibling allogeneic hematopoietic stem cell transplantation and unrelated allogeneic hematopoietic stem cell transplantation(urd-hsct). urd-hsct could expand the range of treatment among β-thalassemia major patients. as recently reported , 68 cases of thalassemia patients at the median age of 15 (2 to 37 ) received unrelated donor bmt. according to pesaro rating classification, 14 patients were attributed to type ⅰ, 16 cases ⅱ type , 38 cases type iii, overall survival and thalassemia free survival rates were 79.3% and 65.8%. a survey among 59 evaluable patients indicated that grade ⅱ \~ ⅳ agvhd occurred in 24 cases (40%) , in which 10 cases (17%) were grade ⅲ \~ ⅳ agvhd. similar results were seen in other reports, 21 patients received unrelated donor bmt, with a 2-year thalassemia free survival rate of 71%. gvhd happened in 3 cases, and 3 patients died. our institution has conducted a total of 10 cases of urd-hsct to treat severe thalassemia, using methotrexate + cyclosporine a+ mycophenolate mofetil to prevent graft-versus-host disease, 9 cases of disease-free survival, 1 case with graft rejection. incidence of ⅲ-ⅳ severe acute graft-versus-host disease (agvhd) was 20%. severe agvhd incidence was 20%. our research group has found there is a high risk to develop agvhd, especially severe agvhd for heavy thalassemia patients who receive urd-hsct, which seriously affects the prognosis and survival, while increasing medical costs and the financial burden on the patients' families. the key factor affecting urd-hsct's success is gvhd. thus effective prevention and treatment of gvhd is a prerequisite to ensure a successful transplant. cd25 is a humanized monoclonal igg1,with murine anti-human il-2ra chain complement determining region retained. il-2ra chain expressed only on the surface of activated cytotoxic t cells, which could convert the il-2r complexes into a higher affinity. the feature that il-2ra distributes only on the surface of activated lymphocytes indicates it's a ideal target when designing the policy to scavenge antigen-specific allogeneic reactive t cells. in vitro experiments, cd25 monoclonal antibody binds specifically with il-2ra+ cells by inhibiting il-2 binding to its receptor competitively. basiliximab has now been used as first-line medication for agvhd treatment, as well as the combined prevention of hematologic malignancies urd-hsct treatment . however as for thalassemia major urd-hsct, few cases have been reported. this study was aimed at the high incidence of agvhd, especially severe agvhd in thalassemia major urd-hsct. basiliximab was added to the original prevention program. the agvhd incidence, implantation rate, transplant-related mortality, infection incidence would be observed. it is hopeful to reduce the agvhd incidence after urd-hsct and promote curative effect.

Eligibility criteria:
inclusion criteria: 1. a diagnosis of tm with hemoglobin electrophoresis, a genetic diagnosis of -thalassemia by dna analysis, and blood transfusion dependence; 2. a cardiac ejection fraction \>50%; 3. normal pulmonary function tests and pulmonary examination results; 4. normal kidney function. exclusion criteria: 1. aspartate aminotransferase level \>4- fold the upper limit of normal range in our institution's laboratory criteria; 2. uncontrolled bacterial, viral, or fungal infection; 3. positive serology for hiv; 4. cytomegalovirus (cmv) or epstein-barr virus (ebv) copy number \>200 copies/ml in blood by quantitative pcr. patients positive for hepatitis c or hepatitis b virus were also excluded. (8) other circumstances which do not meet the inclusion criteria

Keywords: beta-thalassemia major graft-versus-host disease basiliximab allogeneic hematopoietic stem cell transplantation matched unrelated donors