Fludarabine melphalan reduced intensity conditioning vs radiation-based myeloablative conditioning in patients undergoing allogeneic transplantation for acute myeloid leukemia with measurable residual disease

Amanda Blackmon; Michelle Afkhami; Dongyun Yang; Sally Mokhtari; Yazeed Samara; Hoda Pourhassan; Brian Ball; Amandeep Salhotra; Vaibhav Agrawal; Karamjeet Sandhu; Amrita Desai; Salman Otoukesh; Shukaib Arslan; Idoroenyi Amanam; Paul Koller; Jose Tinajero; Ahmed Aribi; Ibrahim Aldoss; Pamela Becker; Andy Artz; Haris Ali; Anthony Stein; Eileen Smith; Vinod Pullarkat; Stephen J Forman; Guido Marcucci; Ryotaro Nakamura; Monzr M Al Malki

doi:10.1038/s41409-024-02491-0

Fludarabine melphalan reduced intensity conditioning vs radiation-based myeloablative conditioning in patients undergoing allogeneic transplantation for acute myeloid leukemia with measurable residual disease

Bone Marrow Transplant. 2024 Dec 18. doi: 10.1038/s41409-024-02491-0. Online ahead of print.

Authors

Amanda Blackmon¹, Michelle Afkhami², Dongyun Yang³, Sally Mokhtari⁴, Yazeed Samara⁵, Hoda Pourhassan⁵, Brian Ball⁵, Amandeep Salhotra⁵, Vaibhav Agrawal⁵, Karamjeet Sandhu⁵, Amrita Desai⁵, Salman Otoukesh⁵, Shukaib Arslan⁵, Idoroenyi Amanam⁵, Paul Koller⁵, Jose Tinajero⁵, Ahmed Aribi⁵, Ibrahim Aldoss⁵, Pamela Becker⁵, Andy Artz⁵, Haris Ali⁵, Anthony Stein⁵, Eileen Smith⁵, Vinod Pullarkat⁵, Stephen J Forman⁵, Guido Marcucci⁵, Ryotaro Nakamura⁵, Monzr M Al Malki⁵

Affiliations

¹ : Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA, USA. [email protected].
² : Department of Pathology City of Hope National Medical Center, Duarte, CA, USA.
³ : Department of Computational and Quantitative Medicine, Beckman Research, Institute of City of Hope, Duarte, CA, USA.
⁴ : Department of Clinical and Translational Project Development, City of Hope National Medical Center, Duarte, CA, USA.
⁵ : Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA, USA.

PMID: 39695333
DOI: 10.1038/s41409-024-02491-0

Abstract

Patients with AML and measurable residual disease (MRD) undergoing allogeneic hematopoietic cell transplantation (HCT) may benefit from myeloablative conditioning (MAC) when feasible to reduce relapse risk. Fludarabine-Melphalan (FluMel) is a common reduced intensity conditioning (RIC) regimen; however, data in MRD+ patients is sparse. We performed a retrospective review of AML patients who underwent their first HCT (2016-2021) without morphologic disease at City of Hope who had pre-transplant marrow evaluated for MRD using multicolor flow cytometry (MFC) and received radiation-based MAC or FluMel conditioning. We identified 312 patients; 44 with MRD+ disease pre-HCT. The 24-month overall survival (OS), leukemia-free survival (LFS) and cumulative incidence of relapse (CIR) were 47.7%, 40.9%, and 38.6% in MRD+, and 78.0%, 73.9%, and 14.6% in MRD- patients. Radiation-based MAC was given to 136 (43.5%) patients (n = 20 with MRD+) and FluMel was given to 174 (55.8%) patients (n = 24 with MRD+). In patients with MRD+, there was no statistically significant difference between those who received MAC vs. FluMel in 24-month OS (60% vs. 38%, p = 0.21), or CIR (35% vs. 42%, p = 0.59), respectively. Our data substantiates the adverse impact of MRD in patients with AML undergoing HCT; FluMel is a reasonable option for MRD+ patients unfit for MAC.