A Novel Hybrid Transplantation with Autologous Hematopoietic Stem Cells and Matched Unrelated Cord Blood Stem Cells Is Effecttive and Safe for Relapsed or Refractory Lymphoma: A Pilot Study

Backgroud:

Autologous hematopoietic stem cell transplantation (ASCT) is widely recommended for relapsed or refractory lymphoma as an important second-line salvage therapy. Post-transplant relapse is a main issue due to its lacking of the graft versus tumor effects with routine ASCT. Hereby we present a novel hybrid transplantation with autologous stem cells and matched unrelated cord blood cells for relapsed or refractory lymphoma.

Method A total of 37 patients with relapsed or refractory lymphoma were enrolled from July 2013 to May 30, 2019 in the West China Hospital of Sichuan University. The autologous peripheral blood stem cells were collected and freezed. HLA matched cord blood cells were searched and provided by the Sichuan Cord Blood Bank. Autologous peripheral blood stem cell transplantation (APBSCT) were infused at day 0 and the selected cord blood cells were infused at day+1 with standard BEAM conditioning regimen.

Result The gender distribution was 51.4% female and 48.6% male.The Median age was 37 years old (16-65 years old). The disease characteristics: relapsed or refractory HL 14 cases, relapsed or refractory DLBCL 9 cases, relapsed Burkitt lymphoma 1 case, HGBL with DHL 1 case, DEL 4 cases, Nos 2 cases, DLBCL with high IPI 3 cases. Advanced nasal NK/T cell lymphoma 2 cases, relapdsed EBV-LPD 1 case. The median number of CD34*10⁶/kg for ASCT was 2.35 (1.32-4.58). The median number of total nucleated cord blood cells was 10.2*10⁸ (6.13-17.9) and the CD34+ cord blood cells was 2.72*10⁶ (1.08-5.2). HLA-identical related donor (6/6) was 10.81%, one-antigen-mismatched (5/6) was 72.98%, two-antigen-mismatched (4/6) was 16.21%. All patients were transplanted succesfully with neutrophil recovery of 11days (8-29) and platelet recovery of 14 days (10-120). An early transplanted syndrom with rash or fever were observed in 7 pts (18.9%), while a delayed neutropenia were observed in 5 pts (13.5%). All symptoms were relieved with prednisone therapy. 2 out of 10 pts examined showed sign of microchimerism at 1 month post transplant. With a median 28 months of follow-up (2-73 months), our hybrid transplantation for R/R lymphoma showed that the relapse-free surviaval (RFS) is 90.4% ,and the overall survival (OS) is 86.4%, which is improved remarkablly. The overall OS and RFS were significant different between complete remission (CR) and Non-CR before transplantation (p= 0.002 for OS; p= 0.015 for RFS), but there was no significant difference in the subgroups of HL and NHL.

Conclusion

This preliminary pilot study suggested that the hybrid stem cell transplantation with autologous stem cells and matched cord blood stem cells is effective and safe for the treatment of high risk lymphoma with limited controlable immuno reactions.