Fludarabine and intravenous busulfan conditioning with post-transplantation cyclophosphamide for allogeneic peripheral stem cell transplantation for adult patients with lymphoid malignancies: a prospective single-arm phase II study

Abstract

Post-transplantation cyclophosphamide (PT-Cy) alone or in combination with other immunosuppressive drugs has emerged as a promising strategy in the setting of allogeneic hematopoietic stem cell transplantation. Improved survival rate was reported in lymphoid malignancies following PT-Cy strategy compared with myeloid disease in non-myeloablative bone marrow transplant setting. Thus, we aimed to evaluate the safety and efficacy of PT-Cy combined with cyclosporine as graft-versus-host disease (GVHD) prophylaxis after myeloablative conditioning and T cell-replete peripheral stem cell transplantation in lymphoid malignancies. This single-arm phase II clinical trial (NCT01435447) involving 31 adult patients was conducted from January 2013 to June 2018. The donor-type neutrophil engraftment rate was 100%, and the overall incidence of grade II to IV and grade III to IV acute GVHD was 39% and 24%, respectively. The cumulative incidence rates of chronic GVHD (35%), including moderate to severe forms (10%), were reduced compared with those of the historical group (P=0.03 and P=0.04, respectively). With a median follow-up of 18 months, the estimated 2-year overall and event-free survival was 64.8% (95% confidence interval: 47.8%–86.7%) and 58.4% (95% CI: 41.9%–81.7%), respectively. The 2-year cumulative incidence rate of relapse was 19.5% (95% CI: 9.0%–35.8%), whereas the non-relapse mortality rate was 21.8% (95% CI: 11.3%–38.1%). These results demonstrated the feasibility of PT-Cy as GVHD prophylaxis in this clinical setting. This strategy could significantly reduce the incidence of chronic GVHD and its moderate to severe forms but not of acute GVHD and results in similar survival outcomes compared with the historical group. A prospective study with additional patients is warranted to confirm the role of PT-Cy in lymphoid malignancy.

Keywords

post-transplantation cyclophosphamide / allogeneic hematopoietic stem cell transplantation / lymphoid malignancies

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Acknowledgements

We thank all clinical fellows and the nursing staff from Blood and Marrow Transplantation Center, Department of Hematology, Ruijin Hospital. This study was supported by the National Natural Science Foundation of China (No. 81770187) and the National Key Research and Development Plan of China (No. 2017YFA0104500).

Compliance with ethics guidelines

Ling Wang, Lining Wang, Xing Fan, Wei Tang, and Jiong Hu declare no conflict of interest. This observational study was conducted in accordance with the Declaration of Helsinki, International Conference on Harmonization Good Clinical Practice, and nationally mandated ethical requirements. The study protocol and informed consent document were reviewed and approved by the ethics committee of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine. All study participants provided informed consent.

Electronic Supplementary Material

Supplementary material is available in the online version of this article at https://doi.org/10.1007/s11684-019-0730-8 and is accessible for authorized users.

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