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Fludarabine and antithymocyte globulin-based conditioning regimen combined with post-transplantation cyclophosphamide for haploidentical allogeneic hematopoietic stem cell transplantation in patients with high-risk acute myeloid leukemia and myelodysplastic syndrome - 03/02/23

Doi : 10.1016/j.retram.2022.103360 
Junjie Cao a, ⁎ , Renzhi Pei a, Ying Lu a, ⁎, Zhongzheng Zheng b, Zhiyang Yuan b, Daiyang Li b, Pisheng Zhang a, Xuhui Liu a, Dong Chen a, Xiaohong Du a, Lieguang Chen a, Shuangyue Li a, Peipei Ye a, Tiantian Wang a
a Department of Hematology, The Affiliated People's Hospital of Ningbo University, Ningbo, Zhejiang Province, China 
b Shanghai Tissuebank Biotechnology Co., Ltd, Shanghai, China 

⁎Corresponding author.

Abstract

Introduction

Relapse and graft-versus-host disease (GVHD) are the important complications influencing mortality for patients with high-risk acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). GVHD prophylaxis based on post-transplant cyclophosphamide (PTCy) or antithymocyte globulin (ATG) is widely used in haploidentical HSCT (haplo-HSCT).

Objective

We developed a modified intensified conditioning regimen including fludarabine (Flu) and investigated the effect of ATG-PTCy combination on transplant outcomes in high-risk AML and MDS compared with those patients who received only ATG as GVHD prophylaxis.

Methods

A total of 80 patients with high-risk AML and MDS were divided into two groups and assigned to one-to-one pairing.

Results

The modified ATG-PTCy group had more infused mononuclear cells, CD34-positive cells and CD3-positive cells than those in the ATG group (P < 0.05). The amount of platelet transfusion was higher in the ATG group than the modified ATG-PTCy group [2 (range, 1–6) U vs 2 (range, 1–5) U, P = 0.005]. The median of platelet recovery was better in the modified ATG-PTCy group than in the ATG group (12 days vs 13 days,P = 0.041). The infection rates of bacteria, fungi and virus at 100 days after transplantation were similar in both groups. Compared with the ATG group, individuals who received the modified ATG-PTCy regimen had higher 2-year GVHD- and relapse-free survival(GRFS) [60.0% (95%CI, 44.9–75.1%) vs 34.8% (95%CI, 19.9–49.7%), P = 0.028]; lower 180-day incidence of II-IV acute GVHD (aGVHD) [15.0% (95%CI, 4.0–26.0%) vs 39.8% (95%CI, 23.9–55.7%), P = 0.029]; lower 1-year incidence of moderate to severe chronic GVHD (cGVHD) [2.9% (95%CI, 2.0–3.8%) vs 19.6% (95%CI, 5.3–33.9%), P = 0.039]; and without an increase in the 2-year cumulative incidence of relapse (CIR) [19.5% (95%CI, 6.6–32.4%) vs 30.4% (95%CI, 15.3–45.5%), P = 0.291].

Conclusions

High-dose stem cells can promote blood cell implantation. The modified ATG-PTCy combination was associated with decreased risk of aGVHD and cGVHD, no increased risk of recurrence, and improved GRFS. It represents an effective strategy for high risk AML and MDS.

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Keywords : Acute myeloid leukemia, Conditioning regimens, Fludarabine, haploidentical allogeneic hematopoietic stem cell transplantation, Post-transplantation cyclophosphamide


Mappa


 Source of fund
This research was supported in part by the Ningbo and Yinzhou District Social and Development project(2016C51018, and YZ2017-59), Ningbo Public welfare project (2019C50071), China.


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