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. 2019 Sep 14;40(9):713-719.
doi: 10.3760/cma.j.issn.0253-2727.2019.09.001.

[Effects of chemotherapy combined with donor lymphocyte infusion on chronic graft-versus-host disease and prognosis in minimal residual disease positive patients after allogeneic hematopoietic stem cell transplantation]

[Article in Chinese]
Y X Shi  1 , X H Zhang  2 , L P Xu  2 , Y Wang  2 , C H Yan  2 , H Chen  2 , Y Y Chen  2 , K Y Liu  2 , X J Huang  2 , X D Mo  2
Affiliations

[Effects of chemotherapy combined with donor lymphocyte infusion on chronic graft-versus-host disease and prognosis in minimal residual disease positive patients after allogeneic hematopoietic stem cell transplantation]

[Article in Chinese]
Y X Shi et al. Zhonghua Xue Ye Xue Za Zhi. .

Abstract
in English, Chinese

Objective: To explore clinical features and severity of chronic graft- versus- host disease (cGVHD) after chemotherapy plus donor lymphocyte infusion (Chemo-DLI) in a consecutive cohort of acute leukemia patients who were minimal residual disease (MRD) positive after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: The global scoring system proposed by National Institutes of Health (NIH) Consensus Conference was used to identify the characteristics and severity of cGVHD in patients who MRD positive after Chemo-DLI. Results: 54 (59.3%) patients were diagnosed with cGVHD after Chemo-DLI, with the median time of onset of 70 (13-504) days. There were 6 cases (6.6%) of mild cGVHD, 21 cases (23.1%) of moderate cGVHD and 27 cases (29.7%) of severe cGVHD.The 5-year cumulative incidence of relapse after Chemo-DLI was 61.9% (95%CI 45.3%-78.5%) , 15.1% (95%CI 1.1%-29.1%) , and 26.6% (95%CI 9.2%-44.0%) (χ(2)=18.901, P<0.001) in non-cGVHD, mild to moderate cGVHD, and severe cGVHD groups, respectively. The 5-year cumulative incidence of relapse after Chemo-DLI was 61.9% (95%CI 45.3%-78.5%) , 19.9% (95%CI 8.1%-31.7%) , and 28.6% (95%CI 0.0%-65.0%) (χ(2)=18.307, P<0.001) in non-cGVHD, classical cGVHD, and overlap syndrome groups, respectively. cGVHD was not associated with non-relapse morality after Chemo-DLI. Probabilities of 5-year leukemia-free survival (LFS) after Chemo-DLI were 24.0% (95%CI 9.1%-38.9%) , 77.2% (95%CI 60.8%-93.6%) , and 64.9% (95%CI 45.7%-84.1%) (χ(2)=24.447, P<0.001) in non-cGVHD, mild to moderate cGVHD, and severe cGVHD groups, respectively. Probabilities of 5-year LFS after Chemo-DLI were 24.0% (95%CI 9.1%-38.9%) , 75.5% (95%CI 62.7%-88.3%) , and 42.9% (95%CI 1.8%-84.0%) (χ(2)=25.665, P<0.001) in non-cGVHD, classical cGVHD, and overlap syndrome groups, respectively. Probabilities of 5-year overall survival (OS) after Chemo-DLI were 50.0% (95%CI 31.1%-68.9%) , 87.9% (95%CI 74.7%-100.0%) , and 71.0% (95%CI 52.0%-90.0%) (χ(2)=9.517, P=0.009) in non-cGVHD, mild to moderate cGVHD, and severe cGVHD groups, respectively. Probabilities of 5-year OS after Chemo-DLI were 50.0% (95%CI 31.1%-68.9%) , 83.9% (95%CI 72.8%-95.0%) , and 51.4% (95%CI 6.2%-96.6%) (χ(2)=10.673, P=0.005) in non-cGVHD, classical cGVHD, and overlap syndrome groups, respectively. In multivariate analysis, patients receiving allo-HSCT in first complete remission stage and classical cGVHD after Chemo-DLI were associated with lower relapse risk and better survival. Conclusions: These findings highlight the close relation between cGVHD and the graft-versus-leukemia effect in patients who were MRD positive and received Chemo-DLI after allo-HSCT. However, overlap syndrome could not improve the clinical outcomes of these patients.

目的： 探讨异基因造血干细胞移植（allo-HSCT）后微小残留病（MRD）阳性患者接受化疗联合供者淋巴细胞输注（Chemo-DLI）后慢性移植物抗宿主病（cGVHD）的临床特点以及其严重程度对患者预后的影响。 方法： 纳入接受allo-HSCT后出现MRD阳性的急性白血病患者，给予Chemo-DLI治疗，采用美国国立卫生研究院（NIH）标准评估cGVHD的特点及严重程度，并分析其对预后的影响。 结果： 共有54例（59.3%）患者在Chemo-DLI后出现cGVHD，中位发生时间为DLI后70（13~504）d。分别有6例（6.6%）、21例（23.1%）、27例（29.7%）患者发生轻度、中度、重度cGVHD。未发生cGVHD、轻中度cGVHD、重度cGVHD患者Chemo-DLI后5年复发率分别为61.9%（95%CI 45.3%~78.5%）、15.1%（95%CI 1.1%~29.1%）、26.6%（95%CI 9.2%~44.0%）（χ(2)=18.901，P<0.001）。未发生cGVHD、经典型cGVHD、重叠综合征患者Chemo-DLI后5年复发率分别为61.9%（95%CI 45.3%~78.5%）、19.9%（95%CI 8.1%~31.7%）、28.6%（95%CI 0.0%~65.0%）（χ(2)=18.307，P<0.001）。cGVHD与治疗后的非复发死亡无关。未发生cGVHD、轻中度cGVHD、重度cGVHD患者Chemo-DLI后5年无白血病生存（LFS）率分别为24.0%（95%CI 9.1%~38.9%）、77.2%（95%CI 60.8%~93.6%）、64.9%（95%CI 45.7%~84.1%）（χ(2)=24.447，P<0.001）。未发生cGVHD、经典型cGVHD、重叠综合征患者Chemo-DLI后5年LFS率分别为24.0%（95%CI 9.1%~38.9%）、75.5%（95%CI 62.7%~88.3%）、42.9%（95%CI 1.8%~84.0%）（χ(2)=25.665，P<0.001）。未发生cGVHD、轻中度cGVHD、重度cGVHD患者Chemo-DLI后5年总生存（OS）率分别为50.0%（95%CI 31.1%~68.9%）、87.9%（95%CI 74.7%~100.0%）、71.0%（95%CI 52.0%~90.0%）（χ(2)=9.517，P=0.009）。未发生cGVHD、经典型cGVHD、重叠综合征患者Chemo-DLI后5年OS率分别为50.0%（95%CI 31.1%~68.9%）、83.9%（95%CI72.8%~95.0%）、51.4%（95%CI 6.2%~96.6%）（χ(2)=10.673，P=0.005）。多因素分析显示，移植前处于第1次完全缓解期、经典型cGVHD与Chemo-DLI后较低的复发风险和较好的生存相关。 结论： 在allo-HSCT后MRD阳性患者中，Chemo-DLI干预后的cGVHD可以降低急性白血病患者的复发风险并改善生存；表现为重叠综合征的患者，需要积极控制cGVHD以改善预后。.

Keywords: Allogeneic hematopoietic stem cell transplantation; Chronic graft-versus-host disease; Donor lymphocyte infusion; Minimal residual disease.

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Figures

图1
图1. 异基因造血干细胞移植后MRD阳性患者Chemo-DLI后不同严重程度cGVHD患者的复发曲线
MRD：微小残留病；Chemo-DLI：化疗联合供者淋巴细胞输注；cGVHD：慢性移植物抗宿主病
图2
图2. 异基因造血干细胞移植后MRD阳性患者Chemo-DLI后不同类型cGVHD患者的复发曲线
MRD：微小残留病；Chemo-DLI：化疗联合供者淋巴细胞输注；cGVHD：慢性移植物抗宿主病
See this image and copyright information in PMC

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