Feasibility of TBI-Augmented Reduced Toxicity Conditioning Regimen with ATG/PTCy Combination for Haploidentical Donor Transplantation in Adult Acute Lymphoblastic Leukemia.
Jaehyun Ahn, Daehun Kwag, Gi June Min, Sung-Soo Park, Silvia Park, Sung-Eun Lee, Byung-Sik Cho, Ki-Seong Eom, Yoo-Jin Kim, Hee-Je Kim, Chang-Ki Min, Seok-Goo Cho, Jae-Ho Yoon
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引用次数: 0
Abstract
Background: Haploidentical donor transplantation (HIDT) with post-transplant cyclophosphamide (PTCy)-based graft-versus-host disease (GVHD) prophylaxis is a promising alternative donor option for adults with high-risk acute lymphoblastic leukemia (ALL). However, the optimal conditioning regimen and GVHD prophylaxis strategy in this patient population remain unclear.
Methods: We evaluated a newly optimized reduced-toxicity conditioning (RTC) regimen which consisted of fludarabine 150 mg/m2, melphalan 100 mg/m2, and low-dose total body irradiation 400 cGy (FMTBI) with GVHD prophylaxis using ATG/PTCy combination in 26 adult patients with ALL undergoing HIDT. We compared the new regimen to 52 historical controls receiving fludarabine 150 mg/m2 plus busulfan 9.6 mg/kg (FB) with ATG. Key endpoints included disease-free survival (DFS), overall survival (OS), GVHD-and-relapse-free survival (GRFS), relapse, non-relapse mortality (NRM), and post-transplantation immune reconstitution.
Results: At one year, the FMTBI group had higher DFS (80.4% vs. 51.9%, p=0.024) and a trend toward improved GRFS (61.0% vs. 34.6%, p=0.073). Relapse incidence was slightly lower (11.9% vs. 32.7%, p=0.059), particularly in the CNS. The cumulative incidence of moderate to severe chronic GVHD was lower (0.0% vs. 11.5%, p=0.074) in the FMTBI group. OS (82.9% vs. 78.8%, p=0.465) and NRM (7.7% vs. 15.4%, p=0.342) rates were similar. NK/NKT cell recovery was transiently delayed at 3 months after FMTBI regimen but normalized by 6 months.
Conclusions: Our newly optimized FMTBI with ATG/PTCy combination showed improved DFS and relapse control while reducing chronic GVHD compared to historical FB with ATG alone in HIDT for adult ALL.