Allogeneic hematopoietic stem cell transplantation for intermediate cytogenetic risk acute myeloid leukemia

doi:10.3969/j.issn.2095-4344.2017.09.025

Abstract

Abstract:

BACKGROUND: Previous studies have shown that HLA-identical sibling allogeneic peripheral blood hematopoietic stem celltransplantation (allo-HSCT) provides higher disease-free and overall survival rates for patients with intermediate cytogenetic risk acute myeloid leukemia (AML) in complete remission (CR). But prognosis factors have not been fully defined.

OBJECTIVE: To evaluate the outcome of patients with intermediate cytogenetic risk AML undergoing HLA-matched allo-HSCT in CR, and to analyze the prognostic factors.

METHODS: Fifty cases of intermediate cytogenetic risk AML in CR receiving HLA-matched allo-HSCT from January 2009 to January 2015 were retrospectively analyzed. Primary outcome measures of the study included overall survival (OS), relapse rate and non-relapse mortality.

RESULTS AND CONCLUSION: The 4-year OS of the study population reached to 64%, and the relapse rate and NRM reached to 18% and 20% respectively. Incidence of acute graft-versus-host disease was 26%. Different prognosis was observed between female donor/male recipient (FDMR) combination transplant and control (4-year OS: 50% vs. 71.9%, P=0.041), between patients requiring more than one course of induction chemotherapy to achieve CR and control (4-year OS: 40% vs. 70%, P=0.038), between older age (≥ 40 years) and control (4-year OS: 44.4% vs. 68.3%, P=0.056). The 4-year OS for matched sibling donor and matched unrelated donor was 63.2% and 66.7% (P=0.427), respectively. Further analysis revealed significantly high non-relapse mortality in FDMR combination transplant (P=0.024) and older age (≥ 40 years; P=0.043). Multivariate analysis revealed three negative prognostic factors: FDMR combination (P=0.031, RR=1.38, 95% CI: 1.03-1.95), requiring more than one course of induction chemotherapy to achieve CR (P=0.016, RR=1.46, 95% CI: 1.10-1.98) and older age (≥ 40 years; P=0.024, RR=1.63, 95% CI: 1.32-2.12). To conclude, HLA-matched allo-HSCT is a choice for the intermediate cytogenetic risk AML case in CR. FDMR combination, requiring more than one course of induction chemotherapy to achieve CR and older age (≥ 40 years) are confirmed as risk factors of poor prognosis for HLA-matched allo-HSCT patients with intermediate cytogenetic risk AML in CR. To these cases, the donor-recipient sex combination is more important than the donor type in donor selection.

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

Key words: Leukemia, Myeloid, Acute, Hematopoietic Stem Cell Transplantation, XYY Karyotype, Tissue Engineering

CLC Number:

R394.2

Zhang Wen-hui, Chi Kai-kai, Chen Yu-qing, Yang Jing, Zhu Zun-min, Sun Kai, Zhang Yin . Allogeneic hematopoietic stem cell transplantation for intermediate cytogenetic risk acute myeloid leukemia[J]. Chinese Journal of Tissue Engineering Research, 2017, 21(9): 1450-1455.

Figures/Tables 2

2.2 造血重建 50例患者均获得造血重建。中性粒细胞重建时间为13(10-25) d，血小板重建时间为14(9-40) d。移植后30-40 d进行植活证据指标检测提示异体造血干细胞在受者体内完全植活。 2.3 移植物抗宿主病发生率 13例(26%)患者移植后出现急性移植物抗宿主病，其中4例(8%)患者发生重度急性移植物抗宿主病；21例(42%)患者发生慢性移植物抗宿主病。 2.4 移植后复发、移植相关死亡、生存率及死亡原因 50例移植患者中共有9例(18%)复发，其中骨髓复发8例，髓外复发1例，中位复发时间为12(2-40)个月，随访期末，只有1例骨髓复发患者带病存活，复发死亡8例。 50例移植患者中共10例(20%)死于非白血病复发移植相关并发症，其中包括急性移植物抗宿主病2例、巨细胞病毒感染1例、出血性膀胱炎2例、肺部真菌感染2例、移植物抗宿主病相关性间质性肺炎1例、卡氏肺孢子虫肺炎1例、急性呼吸窘迫综合征1例。随访期末，共有32例患者存活，4年总体生存率为64%。对移植相关非复发死亡率危险因素的分析发现，女性供者男性受者配对患者移植相关非复发死亡率明显高于非女性供者男性受者配对患者(分别为33%和12%，P=0.044)、年龄≥40岁的患者移植相关非复发死亡率明显高于年龄< 40岁的患者(分别为44%和15%，P=0.029)，见图2。未发现非亲缘移植、移植前大于1个疗程才能达完全缓解、高白细胞(诊断时白细计数> 50×109 L-1)和髓外浸润与移植相关非复发死亡率相关(P均> 0.05)。作者又进一步分析了与复发相关的危险因素，未发现上述因素与疾病复发率的相关性(P均> 0.05)。 2.5 预后因素分析作者分析了与移植预后相关的危险因素，包括年龄≥40岁，女性供者男性受者配对移植、非亲缘移植、移植前大于1个疗程才能达完全缓解、高白细胞和髓外浸润。单因素分析发现，女性供者男性受者配对移植、移植前大于1个疗程才能达完全缓解、年龄≥40岁是预后不良的危险因素。女性供者男性受者配对移植病例(n=18)和非女性供者男性受者配对移植病例(n=32)，4年总体生存率分别为50%和72%(P=0.041，图3)。移植前大于1个疗程才能达完全缓解的病例(n=10)和1个疗程达到完全缓解的病例(n=40)，4年总体生存率分别为40%和70%(P=0.038)。年龄≥40岁的病例(n=9)和年龄< 40岁的病例(n=41)，4年总体生存率分别为44%和68%(P=0.056)。非亲缘移植、高白细胞和髓外浸润对总体生存率的影响差异无显著性意义(P均> 0.1，表1)。将单因素分析中P < 0.10的预后危险因素纳入了多因素分析。结果显示女性供者男性受者配对移植、移植前大于1个疗程才能达完全缓解、年龄≥40岁均为预后不良的独立危险因素，其相对危险度(RR)分别为1.52(95%CI 1.03-1.95，P=0.031)、1.91(95%CI 1.36-2.41，P=0.016)及1.63(95%CI 1.17-2.06，P=0.024)，见表1。"

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