Sequential Intensified Conditioning Followed By Early Tapering Immunosuppressants and DLI In Allogeneic Hematopoietic Stem Cell Transplantation For Refractory/Recurrent T Lymphoblastic Lymphoma
Authors: Dai Min , Zhou Hongsheng , Huang Fen , Zhang Yu , Fan Zhiping , Guo Xutao , Xu Na , Sun Jing , Liu Qifa 
Published: October 2019

Abstract

Background
FAdult T lymphoblastic lymphoma is an aggressive form of non-Hodgkin lymphoma occurring in predominantly adolescent and young adult men.High-dose chemotherapy followed by autologous or allogeneic transplantation as consolidation for patients in CR1 is controversial. Refractory/recurrent T lymphoblastic lymphoma has poor response to conventional chemotherapy.

Aims
To prospectively evaluate the efficacy of sequential intensified conditioning followed by early tapering immunosuppressants and DLI in allogeneic hematopoietic stem cell transplantation as salvage therapy for refractory/recurrent T lymphoblastic lymphoma.

Methods
18 patients with refractory/recurrent T lymphoblastic lymphoma (male in 16 cases and female in 2 cases) from September 2010 to May 2013 were enrolled in this prospective study, with median age was 31 (range 16-42) years.15 patients received related and 3 unrelated donor transplantation, and 15 patients were HLA-match and 3HLA-mismatched transplantation. The sequential intensified conditioning included fludarabine 30mg/m2/d and cytarabine 2g/ m2/d(on days -10 to -6) ,4.5 Gy total body irradiation/day (on days -5 and -4), cyclophosphamide 60 mg/kg/d and etoposide 15mg/ kg/d (on days -3 and -2). Cyclosporine A was withdrawn rapidly in a stepwise fashion if acute GVHD (aGVHD) did not develop at day +30. Patients without II-IV grade acute graft-versus-host disease received G-CSF mobilized DLI with a dose of ANC 1×106/kg at +60days post-transplantation once monthly until II-IV grade acute graft-versus-host disease (aGVHD) occurr or for 4 doses.

Results
F16 patients(88.88%) achieved complete remission on day +30 and 1 patient died of regimen-related toxicities on day 0,another patient died of septic shock due to VRE septicemia on day +10. With a median follow-up of 28 months post-transplation(range:2-33 months), only 2 patients relapsed and 1 died of relapse on day +95. Till now, 14 patients were alive and 1 patient died of TMA on day +68.The 2-year overall survival and disease-free survival post-transplation were 77.78%,72.22% respectively. The 2 year incidence of relapse was 11.11%. All death patients except the relapsed one received more than 10 courses chemotherapy before transplantation.

Conclusions
Our data indicates that the sequential intensified conditioning and rapid tapering immunosuppressants as well as DLI in the early stage after allo-HSCT might be an effective method for refractory/recurrent T lymphoblastic lymphoma. Regimen-related toxicities were tolerable and too much chemotherapy courses before transplantation maybe increased the risk of complications.

Disclosures:
Liu: It was supported by Science and Technology Program of Guangzhou of China (11A72121174).: Research Funding; It was supported by National Public Health Grand Research Foundation (Grant No. 201202017), National Natural Science Foundation of China (Grant No.81000231, No.81270647).: Research Funding; It was supported by 863 Program (No. 2011AA020105).: Research Funding.