A Clinical Study On Rituximab for Probable and Proven EBV Disease Post Haematopoietic Stem-Cell Transplantation

EBV disease manifest as EBV-associated tumors lymphoproliferative disease (PTLD) and probable EBV disease. It is a severe complication post haematopoietic stem-cell transplantation (HSCT) and may cause to death in very short time. We analyse the effect and safety of Rituximab for probable and proven EBV disease (PTLD) in HSCT recipients in our center retrospectively.

Diagnosis of EBV disease was based on the criteria described in guidelines from the Second European Conference on Infections in Leukemia. Between June 2006 and June 2012, 33 patients were diagnosed EBV disease and received Rituximab. 20 cases are Male, 13 cases female; the median age of the patients was 21 years (3–46 years). 18 cases with AML for HSCT, 10 cases with ALL, 1 case with MDS, 1case with CML, 2 cases with SAA, 1 case with Granulocytic sarcoma; 28 cases receive Haploidentical HSCT, 3 cases receive unrelated volunteer PBSCT,1 case received unrelated CBT,1 case received sibling matched donor HSCT for SAA. Conditioning regimen including modified BUCY/ATG or CY+ATG, GVHD prophylaxis include CSA/MTX/MMF. 11 cases diagnosed as PTLD with lymphanode pathology and 22 as probable EBV disease. one organ was involved in 13 cases, multiple organs involved in 20 cases. Patients received 3(1–6) infusions of 375 mg/m2 at one week interval.

There were no middle or severe side effects occur during Rituximab infusion. The overall response rate was 87.9%, the CR rate was 75.8%. The 1^st, 2^nd, 3^rd,4^th,8^th week cumulative CR incidence from onset Rituxmab is 18.4±6.8%□A31.7±8.2%□A58.8±9.0%□A76.8±7.9%□A82.6+7.8% respectively. The cumulative incidence of CR is higer in single organ involved patients than in multiple organs involved patients, the 1^st, 2^nd, 3^rd,8^th week cumulative CR incidence from onset Rituxmab is 15.4±10.0% vs 10.0±6.7%□A69.2+12.8% vs 30.7+10.5%□A74.6+10% vs 52.0±11.5%, 100% vs 64.0±11.3% respectively, (p=0.015). The cumulative incidence of CR is higer in probable EBV disease group than that in documented PTLD group, the 1^st, 2^nd, 3^rd,8^th week cumulative CR incidence from onset Rituxmab is 13.6+7.3% vs 9.1+8.7%□A54.5+10.6% vs 29.3+14.3%□A77.3+8.9 % vs 39.4±15.4%, 87.9% ±7.4 vs 63.6±16.2% respectively, (p=0.050). Of 25 CR cases,19 patients are alive with no evidence of disease, all of 8 patients without CR died. The one-year and two-year projected survival is 76.8+7.7%% and 40.1+11.9% with a median follow-up 11.5(2.3–26) of months in surviving patients. The one-year and two-year projected survival from onset of Rituximab therapy is higher in single organ group than that in multiple organ group, it is 74.1±16.1% vs 45.7+11.8% and 74.1±16.1 vs 24.4±13.0% (p=0.015) respectively. The one-year and two-year projected survival from onset of Rituximab therapy is higher in probable EBV disease group than that in documented PTLD group, it is 85.2±8.0% vs 18.2±11.6% and 55.9±18.5 vs 18.2.4±11.6% (p=0.002) respectively.

The use of rituximab appears to be a safe and relatively efficient therapy in EBV disease. The better response may get in early stage, that is one organ involved and probable EBV disease. So, we suggest Rituximab should gave based on probable EBV disease in early stage meanwhile Pathology was try to get as soon as possible.

No relevant conflicts of interest to declare.