Comparison of Conventional Cyclophosphamide versus Fludarabine-Based Conditioning in High-Risk Aplastic Anemia Patients Undergoing Matched-Related Donor Transplantation

Raheel Iftikhar; Qamar Un Nisa Chaudhry; Tariq Mehmood Satti; Syed Kamran Mahmood; Tariq Ghafoor; Ghassan Umair Shamshad; Nighat Shahbaz; Mehreen Ali Khan; Tariq Azam Khattak; Jahanzeb Rehman; Muhammad Farhan; Saima Humayun; Humera Haq; Syeda Ammaara Anwaar Naqvi; Faiz Anwer; Humayoon Shafique Satti; Parvez Ahmed

doi:10.2991/chi.d.200426.001

Comparison of Conventional Cyclophosphamide versus Fludarabine-Based Conditioning in High-Risk Aplastic Anemia Patients Undergoing Matched-Related Donor Transplantation

Clin Hematol Int. 2020 May 18;2(2):82-91. doi: 10.2991/chi.d.200426.001. eCollection 2020 Jun.

Authors

Raheel Iftikhar¹, Qamar Un Nisa Chaudhry¹, Tariq Mehmood Satti¹, Syed Kamran Mahmood¹, Tariq Ghafoor¹, Ghassan Umair Shamshad¹, Nighat Shahbaz¹, Mehreen Ali Khan¹, Tariq Azam Khattak¹, Jahanzeb Rehman¹, Muhammad Farhan¹, Saima Humayun¹, Humera Haq¹, Syeda Ammaara Anwaar Naqvi¹, Faiz Anwer², Humayoon Shafique Satti³, Parvez Ahmed⁴

Affiliations

¹ Department of Hematology and Stem Cell Transplant, Armed Forces Bone Marrow Transplant Center/National Institute of Blood and Marrow Transplant, Rawalpindi 46000, Pakistan.
² Department of Hematology, Medical Oncology, Taussig Cancer Center, Cleveland Clinic, Cleveland, OH 44195, USA.
³ National University of Medical Sciences, Rawalpindi 46000, Pakistan.
⁴ Department of Hematology-Oncology and Stem Cell Transplant, Quaid-e-Azam International Hospital, Islamabad 44000, Pakistan.

Abstract

Allogeneic stem cell transplant for high-risk aplastic anemia (AA) yields inferior results using conventional cyclophosphamide (CY)-based conditioning. The use of fludarabine (Flu)-based regimens has resulted in improved outcomes in high-risk patients. Limited data are available comparing these two conditioning regimens in such patients. We retrospectively analyzed 192 high-risk patients undergoing matched-related donor transplantation from July 2001 to December 2018. The median age was 19.5 (2-52) years. Patients were divided into 2 groups, Cy²⁰⁰ anti-thymocyte globulin (ATG)²⁰ (Gp1 n = 79) or Flu^120-150 Cy^120-160 ATG²⁰ (Gp2 n = 113). The risk of graft failure was significantly higher in Gp1, and the majority occurred in patients with >2 risk factors (p = 0.02). The incidence of grade II-IV acute graft versus host disease (GVHD) and chronic GVHD was not significantly different between the two groups. The overall survival (OS) of the study cohort was 81.3 %, disease-free survival (DFS) 76.6 % and GVHD-free relapse-free survival (GRFS) was 64.1%. DFS and GRFS were significantly higher in Gp2 as compared to Gp1: DFS 84.1% versus 68.4 % (p = 0.02), GRFS 77.9% versus 54.4% (p = 0.01), respectively. We conclude that Flu-based conditioning is associated with superior OS, DFS and GRFS as compared to the conventional Cy-based regimen in high-risk AA.

Keywords: Aplastic anemia; Cyclophosphamide; Fludarabine; Stem cell transplantation.