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A gemcitabine-based regimen followed by autologous stem cell transplantation show high efficacy and well tolerance in malignant lymphoma

Bone Marrow Transplantation volume 57, pages 1017–1020 (2022)Cite this article

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The combination of 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU/carmustine), etoposide, aracytin, and melphalan (BEAM) followed by autologous stem cell transplantation (ASCT) is widely used for chemo-sensitive patients with relapsed non-Hodgkin’s lymphoma (NHL) and Hodgkin’s lymphoma (HL). However, in 2017, BCNU was in short supply across China; therefore, alternative BEAM conditioning regimens were investigated. A preclinical study demonstrated that combined gemcitabine, busulfan, and melphalan (GBM) had synergistic inhibitory effects on the proliferation of lymphoma cell lines [1]. Further studies showed that GBM conditioning in patients with refractory lymphoid malignancies provided a comparatively safe and active regimen for ASCT and improved the 2-year progression-free survival (PFS) and overall survival (OS) when compared with BEAM in refractory or relapsed HL patients [2,3,4]. On the basis of these promising data, we began testing the GBM conditioning regimen for ASCT in lymphoid patients. However, as melphalan supplies were also limited in China in 2017/2018, cyclophosphamide was routinely substituted [5, 6]; we therefore developed a gemcitabine, busulfan, and cyclophosphamide (GBC) regimen.

For this study, we identified 91 consecutive lymphoma patients who were treated between May 2017 and April 2020 and had previously undergone ASCT with GBC or GBM conditioning: 71 patients in the GBC group and 20 in the GBM group. The main clinical characteristics are shown in Table 1. Pretransplant status was evaluated before ASCT by positron emission tomography (PET) and/or computed tomography (CT) according to published criteria [7]. Thirty-three patients with LBCL, 15 with mantle cell lymphoma, and eight with peripheral T-cell lymphoma were in the first-line treatment group, while 12 patients with HL and nine with LBCL were in the non-first-line treatment group. Thirty-three DLBCL patients received first-line ASCT, most of whom were high-intermediate or high-risk patients (aaIPI = 2–3) with double hit or double expression or positive interim PET2 (Deauville score 4). The study was approved by the Ethics Committee and Human Research Committee of Institute of Hematology & Blood Disease Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College. All patients provided written informed consent prior to transplantation. Compared with the MD Anderson Cancer Center, we adjusted the original dose, mainly because we found the original dose to be more toxic at the time of initial application. Patients were treated with either the GBC regimen: gemcitabine (Hansoh Pharma, Jiangsu, China) (a loading bolus of 75 mg/m2, followed by a continuous infusion of 1800 mg/m2 over 3 h on days −7 and −3), busulfan (DSM Pharmaceuticals, Inc., Greenville, NC 27834, USA) (105 mg/m2 from days −7 to −5), and cyclophosphamide (Baxter Oncology GmbH, Halle, Germany) (50 mg/kg from days −3 to −2), or the GBM regimen: melphalan (Acrotech Biopharma., East Windsor, NJ 08520, USA) at 60 mg/m2 intravenously on days −3 to −2. Peripheral autologous stem cells were reinfused on day 0. The median transplanted CD34+ cell dose was 3.07 × 106/kg (range: 0.71–21.33 × 106/kg).

Table 1 Patient characteristics.
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Fig. 1: Overall survival (OS) and progression-free survival (PFS) curves of patients with malignant lymphoma conditioned with GBC/GBM before autologous stem cell transplantation.

Data availability

The patients’ data used to support the findings of this study are available from the corresponding author upon request.

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Funding

This work was funded under the auspices of the National Natural Science Foundation of China (81970187 and 81900203).

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  1. These authors contributed equally: Huimin Liu, Wei Liu.

Authors and Affiliations

  1. State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 300020, Tianjin, China

    Huimin Liu, Wei Liu, Ru Li, Yang Jiao, Wenyang Huang, Shuhua Yi, Rui Lv, Shuhui Deng, Gang An, Tingyu Wang, Weiwei Sui, Mingwei Fu, Yaozhong Zhao, Lugui Qiu & Dehui Zou

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  1. Huimin Liu
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Contributions

DZ and WL designed the research strategy; HL, RL, and YJ analyzed results; HL wrote the paper; HL and RL collected data; DZ, WL, and LQ edited and provided scientific discussion; WH, SY, RL, SD, GA, TW, WS, MF, and YZ all reviewed and provided scientific discussion.

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Correspondence to Dehui Zou.

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Liu, H., Liu, W., Li, R. et al. A gemcitabine-based regimen followed by autologous stem cell transplantation show high efficacy and well tolerance in malignant lymphoma. Bone Marrow Transplant 57, 1017–1020 (2022). https://doi.org/10.1038/s41409-022-01655-0

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