-
化疗和异基因造血干细胞移植是行之有效的治疗急性白血病(acute leukemia,AL)的方法,随着医学技术的进步,大部分患者可获得完全缓解;但随着无病生存期的延长,仍有部分患者出现AL复发,这已成为AL治疗失败的主要原因[1]。临床上,AL的诊断不依赖于影像学检查方法,骨髓穿刺活检是确切诊断和复发监测的主要方法,但是其存在一定的风险[2-3]。PET/CT在淋巴瘤和实体肿瘤中的应用价值已得到广泛认可,对于可疑的AL髓外浸润灶,也有研究结果证实18F-FDG PET/CT能够比常规影像学方法检出更多的髓外浸润病灶[4-6]。
但关于18F-FDG PET/CT对AL髓内复发的诊断价值,学术界仍存在争议,有学者认为其价值取决于骨髓18F-FDG的摄取模式[7],也有研究者认为取决于18F-FDG的摄取程度[8]。本研究回顾性分析经骨髓移植术后临床可疑复发并行18F-FDG PET/CT显像的AL患者的图像及病历资料,重点探讨18F-FDG PET/CT对髓内复发的诊断价值。
-
81例患者的组织病理学检查(PET/CT检查前1周内)结果显示,7例阴性患者的18F-FDG PET/CT显像检出骨髓阳性摄取病灶,其中2例经组织病理学检查结果证实为AL复发,其余5例经临床随访证实(经化疗后的18F-FDG PET/CT显像结果显示原摄取增高病灶消失)。由表1可知,复发组与无复发组间的性别分布,差异无统计学意义(P=0.081);复发组比无复发组年龄略大,且差异有统计学意义(P=0.040);2组均有6例低热患者,体温37.3~37.8℃;2组患者脾肿大发生率的差异无统计学意义(P=0.224)。
项目 复发组(n=41) 无复发组(n=40) 检验值 P值 年龄(岁, )${{\bar x} } \pm s$ 28.51±8.94 21.70±14.70 t=2.075 0.040 性别[例(%)] χ2=1.321 0.081 男性 24(58.53) 21(52.50) 女性 17(41.16) 19(47.50) 骨髓SUVmax/肝脏SUVmax t=2.186 0.032 ±s$\bar x $ 1.20±0.56 0.89±0.74 极值范围 0.50~2.78 0.28~5.12 附肢骨SUVmax/中轴骨SUVmax t=3.477 0.001 ±s$\bar x $ 1.58±1.38 0.79±0.37 极值范围 0.33~6.07 0.25~1.95 中轴骨SUVmax t=3.367 0.001 ±s$\bar x $ 3.10±1.65 1.99±1.26 极值范围 1.00~7.80 0.70~8.20 发热[例(%)] 6(14.63) 6(15.00) χ2=68.900 0.754 脾肿大[例(%)] 2(4.87) 1(2.50) χ2=2.980 0.224 注:SUVmax为最大标准化摄取值 表 1 81例急性白血病患者的临床及影像学资料
Table 1. The clinical manifestations and imaging features of 81 patients with acute leukemia
-
复发组与无复发组的骨髓SUVmax/肝脏SUVmax比值分别为1.20±0.56、0.89±0.74,差异有统计学意义(t=2.186,P=0.032);2组附肢骨SUVmax/中轴骨SUVmax 比值分别为1.58±1.38、0.79±0.37,差异有统计学意义(t=3.477,P=0.001)。
-
18F-FDG PET/CT代谢参数SUVmax诊断AL髓内复发的效能结果见表2;基于SUVmax的半定量参数诊断AL髓内复发灶的ROC曲线见图1。
参数 ±s$\bar{{x} }$ AUC 95%CI 标准差 P值 临界值 灵敏度(%) 特异度(%) 准确率(%) 骨髓SUVmax/肝脏SUVmax比值 1.20±0.76 0.711 0.598~0.823 0.057 0.001 1.11 48.78(20/41) 90.00(36/40) 69.14(56/81) 附肢骨SUVmax/中轴骨SUVmax比值 1.43±1.24 0.738 0.628~0.848 0.056 <0.01 1.03 56.10(23/41) 87.50(35/40) 71.60(58/81) 中轴骨SUVmax 2.91±1.76 0.770 0.667~0.873 0.053 <0.01 2.05 70.73(29/41) 72.50(29/40) 71.60(58/81) 注:FDG为氟脱氧葡萄糖;PET为正电子发射断层显像术;CT为计算机体层摄影术;ROC为受试者工作特征;SUVmax为最大标准化摄取值;AUC为曲线下面积;CI为可信区间 表 2 81例急性白血病患者的18F-FDG PET/CT半定量参数及ROC曲线对髓内复发病灶的诊断效能
Table 2. Diagnostic efficacy of 18F-fluorodeoxyglucose PET/CT semiquantitative parameters and receiver operating characteristic curve in recurrent bone marrow lesions of 81 patients with acute leukemia
-
经组织病理学检查结果证实,共有41例髓内复发AL患者。以单发或多灶性骨髓摄取为髓内复发的诊断标准时,18F-FDG PET/CT的诊断灵敏度、特异度和准确率分别为71.43%(15/21)、100%(28/28)和87.76%(43/49);以弥漫性摄取为诊断标准时,其灵敏度、特异度和准确率分别为76.92%(20/26)、70.00%(28/40)和72.73%(48/66)。以多灶性摄取+弥漫性摄取为诊断标准时,灵敏度、特异度和准确率分别为85.37%(35/41)、70.00%(28/40)和77.78%(63/81)。在15例多灶性或孤立性摄取中,孤立性摄取2例,其余13例表现为多灶性摄取异常增高,典型病例见图2。复发组的20例弥漫性摄取表现为中轴骨及四肢骨的轻度或明显高于肝脏本底的摄取,且四肢骨髓腔的摄取范围累及长骨骨干和干骺端,尤其以双侧股骨和双侧肱骨更显著,大部分并非完全均匀性摄取,在均匀摄取增高的基础上同时伴有局灶性或结节状摄取(图3)。无复发组的弥漫性摄取呈双侧四肢长骨对称性分布,四肢骨髓腔摄取范围仅累及股骨或肱骨骨干的近段1/3~1/2区域(图4),其中6例合并有低热(体温37.3~37.8℃);髂骨的组织病理学检查结果显示:骨髓增生活跃,粒系细胞/红系细胞、粒系细胞、红系细胞、巨核细胞形态和各阶段细胞数比例未见异常,骨髓中未见异常幼稚细胞。18F-FDG PET/CT结果显示,12例假阳性,6例假阴性,其中2例合并中枢神经系统浸润。
图 2 急性淋巴细胞白血病骨髓移植术后患者(女性,14岁)的18F-FDG PET/CT显像图
Figure 2. 18F-fluorodeoxyglucose PET/CT images of a patient (female, 14 years old) with acute lymphoblastic leukemia after bone marrow transplantation
图 3 急性淋巴细胞白血病骨髓移植术后患者(女性,32岁)的18F-FDG PET/CT显像图
Figure 3. 18F-fluorodeoxyglucose PET/CT images of a patient (female, 32 years old) with acute lymphoblastic leukemia after bone marrow transplantation
图 4 急性髓系白血病骨髓移植术后患者(男性,55岁)的18F-FDG PET/CT最大密度投影图(A)和组织病理学检查图(B,苏木精-伊红染色,×200)
Figure 4. 18F-fluorodeoxyglucose PET/CT maximum density projection imaging and histopathological examination image of a patient (male, 55 years old) with acute myeloid leukemia after bone marrow transplantation
AL复发组的主要表现为骨髓弥漫性摄取增高或多灶性摄取,二者总占比约为85.36%(35/41)。此外,视觉判读结果还显示,复发组骨髓弥漫性摄取18F-FDG的程度要高于无复发组;半定量测量结果显示,复发组患者的中轴骨SUVmax高于无复发组,且差异有统计学意义(4.16±2.03对1.54±0.54,t=3.768, P=0.003)。
18F-FDG PET/CT 对急性白血病骨髓移植术后髓内复发灶的诊断价值
Diagnostic value of 18F-FDG PET/CT for the intramedullary relapse of acute leukemia after bone marrow transplantation
-
摘要:
目的 探讨18F-氟脱氧葡萄糖(FDG) PET/CT对急性白血病(AL)骨髓移植术后髓内复发灶的诊断价值,筛选可用于诊断其复发的半定量参数。 方法 回顾性分析2016年11月至2019年11月于河北燕达医院接受骨髓移植且疑为髓内复发的81例AL患者的18F-FDG PET/CT图像和病历资料,其中男性45例、女性36例,年龄3~55(25.14±15.07)岁。以骨髓活检的组织病理学检查结果为诊断复发的“金标准”,将患者分为复发组(41例)、无复发组(40例),测量并计算所有可疑复发病灶的最大标准化摄取值(SUVmax)及肝脏本底SUVmax,计算附肢骨SUVmax/中轴骨SUVmax和骨髓SUVmax/肝脏SUVmax比值,并以其不同的临界值和受试者工作特征(ROC)曲线进行分析,计算曲线下面积(AUC)和诊断复发的效能。以视觉判读法为参照,分析并计算18F-FDG PET/CT不同半定量参数诊断AL髓内复发灶的效能。2组间半定量参数的比较采用独立样本t检验;计数资料的比较采用Pearson卡方检验。 结果 81例AL患者中,复发组的中轴骨SUVmax高于无复发组(3.10±1.65对1.99±1.26,t=3.367,P=0.001);与无复发组比较,复发组的骨髓SUVmax /肝脏SUVmax比值(1.20±0.56对0.89±0.74)和附肢骨SUVmax /中轴骨SUVmax比值(1.58±1.38对0.79±0.37)均较高,且差异均有统计学意义(t=2.186、3.477,均P<0.05)。基于SUVmax的半定量指标的ROC曲线分析结果显示,以中轴骨SUVmax≥2.05作为判断髓内复发的标准时,其诊断AL复发的灵敏度、特异度和准确率分别为70.73%(29/41)、72.50%(29/40)和 71.60%(58/81),AUC为0.770。视觉判读法结果显示,以多灶性摄取+弥漫性摄取18F-FDG为髓内复发的诊断标准时,其诊断AL复发的灵敏度、特异度和准确率分别为85.37%(35/41)、70.00%(28/40)和77.78%(63/81)。 结论 18F-FDG PET/CT视觉判读法是诊断AL复发简便、可靠的方法,具有较高的诊断效能,基于SUVmax的半定量参数分析是视觉判读法的重要补充。 -
关键词:
- 白血病 /
- 复发 /
- 正电子发射断层显像术 /
- 体层摄影术,X 线计算机 /
- 氟脱氧葡萄糖F18 /
- 最大标准化摄取值
Abstract:Objective To explore the diagnostic efficacy of 18F-fluorodeoxyglucose(FDG) PET/CT on intramedullary relapse of acute leukemia, and screening parameters that can be used to give the diagnosis. Methods The 18F-FDG PET/CT imaging data of 81 patients (45 males and 36 females aged 3–55(25.14±15.07)years) who were clinically diagnosed with suspected intramedullary relapse of acute leukemia in Hebei Yanda Hospital from November 2016 to November 2019 were retrospectively analyzed. All the patients had received bone marrow transplantation. And the histopathological results of bone marrow biopsy were used as "golden standard" of intramedullary relapse. The patients were divided into relapse group (41 cases) and non-relapse group (40 cases). The maximum standardized uptake value (SUVmax) of all the suspected recurrent lesions and SUVmax of normal liver background (liver SUVmax) were measured and calculated. The ratio of appendicular skeleton SUVmax to that of axial skeleton and the ratio of axial skeleton SUVmax to that of normal liver background were calculated respectively. The different cut-off values and area under curve (AUC) based on receiver operating characteristic (ROC) curves were analyzed, and the diagnostic efficacy of 18F-FDG PET/CT on relapse of acute leukemia was explored preliminarily. Visual interpretation was applied as a reference criterion to explore the diagnostic efficacy of 18F-FDG PET/CT on the intramedullary relapse of acute leukemia based on different semiquantitative parameters. Differences in semiquantitative parameters between the two groups were compared by independent sample t-test for measurement data and Pearson chi-square test for qualitative data. Results Axial skeleton SUVmax of the relapse group was higher than that of the non-relapse group (3.10±1.65 vs. 1.99±1.26, t=3.367, P=0.001). Meanwhile, compared with non-relapse group, the ratio of axial skeleton SUVmax to normal liver background SUVmax (1.20±0.56 vs. 0.89±0.74), and the ratio of appendicular skeleton SUVmax to axial skeleton SUVmax (1.58±1.38 vs. 0.79±0.37) were higher than that of relapse group. Both difference has statistics significance (t=2.186, 3.477; both P<0.05). The ROC curve analysis of the semiquantitative index of SUVmax revealed that the sensitivity, specificity, and accuracy of relapse diagnosis were 70.73% (29/41), 72.50% (29/40), and 71.60% (58/81), respectively (AUC=0.770), when axial skeleton SUVmax≥2.05 was used as the criterion of intramedullary relapse. When multifocal+diffuse increased 18F-FDG uptake was used as the criterion of intramedullary relapse, visual evaluation-based results indicated sensitivity, specificity, and accuracy of 85.37% (35/41), 70.00% (28/40), and 77.78%(63/81), respectively. Conclusions Visual evaluation based on 18F-FDG PET/CT is a simple and reliable method for diagnosing acute leukemia relapse, and has high diagnostic efficacy. Based on SUVmax semi-quantitative parameter analysis is a useful supplement to visual evaluation. -
表 1 81例急性白血病患者的临床及影像学资料
Table 1. The clinical manifestations and imaging features of 81 patients with acute leukemia
项目 复发组(n=41) 无复发组(n=40) 检验值 P值 年龄(岁, )${{\bar x} } \pm s$ 28.51±8.94 21.70±14.70 t=2.075 0.040 性别[例(%)] χ2=1.321 0.081 男性 24(58.53) 21(52.50) 女性 17(41.16) 19(47.50) 骨髓SUVmax/肝脏SUVmax t=2.186 0.032 ±s$\bar x $ 1.20±0.56 0.89±0.74 极值范围 0.50~2.78 0.28~5.12 附肢骨SUVmax/中轴骨SUVmax t=3.477 0.001 ±s$\bar x $ 1.58±1.38 0.79±0.37 极值范围 0.33~6.07 0.25~1.95 中轴骨SUVmax t=3.367 0.001 ±s$\bar x $ 3.10±1.65 1.99±1.26 极值范围 1.00~7.80 0.70~8.20 发热[例(%)] 6(14.63) 6(15.00) χ2=68.900 0.754 脾肿大[例(%)] 2(4.87) 1(2.50) χ2=2.980 0.224 注:SUVmax为最大标准化摄取值 表 2 81例急性白血病患者的18F-FDG PET/CT半定量参数及ROC曲线对髓内复发病灶的诊断效能
Table 2. Diagnostic efficacy of 18F-fluorodeoxyglucose PET/CT semiquantitative parameters and receiver operating characteristic curve in recurrent bone marrow lesions of 81 patients with acute leukemia
参数 ±s$\bar{{x} }$ AUC 95%CI 标准差 P值 临界值 灵敏度(%) 特异度(%) 准确率(%) 骨髓SUVmax/肝脏SUVmax比值 1.20±0.76 0.711 0.598~0.823 0.057 0.001 1.11 48.78(20/41) 90.00(36/40) 69.14(56/81) 附肢骨SUVmax/中轴骨SUVmax比值 1.43±1.24 0.738 0.628~0.848 0.056 <0.01 1.03 56.10(23/41) 87.50(35/40) 71.60(58/81) 中轴骨SUVmax 2.91±1.76 0.770 0.667~0.873 0.053 <0.01 2.05 70.73(29/41) 72.50(29/40) 71.60(58/81) 注:FDG为氟脱氧葡萄糖;PET为正电子发射断层显像术;CT为计算机体层摄影术;ROC为受试者工作特征;SUVmax为最大标准化摄取值;AUC为曲线下面积;CI为可信区间 -
[1] Dholaria B, Savani BN, Hamilton BK, et al. Hematopoietic cell transplantation in the treatment of newly diagnosed adult acute myeloid leukemia: an evidence-based review from the American society of transplantation and cellular therapy[J]. Transplant Cell Ther, 2021, 27(1): 6−20. DOI: 10.1016/j.bbmt.2020.09.020. [2] Percival ME, Lai C, Estey E, et al. Bone marrow evaluation for diagnosis and monitoring of acute myeloid leukemia[J]. Blood Rev, 2017, 31(4): 185−192. DOI: 10.1016/j.blre.2017.01.003. [3] Abelson S, Collord G, Ng SWK, et al. Prediction of acute myeloid leukaemia risk in healthy individuals[J]. Nature, 2018, 559(7714): 400−404. DOI: 10.1038/s41586-018-0317-6. [4] Zhou WL, Wu HB, Wang LJ, et al. Usefulness and pitfalls of F-18-FDG PET/CT for diagnosing extramedullary acute leukemia[J]. Eur J Radiol, 2016, 85(1): 205−210. DOI: 10.1016/j.ejrad.2015.11.019. [5] de Bonilla Damiá Á, Fernández López R, Acevedo Báñez I, et al. 18F-FDG PET/CT for extramedullary relapse of acute leukemia of ambiguous lineage[J/OL]. Rev Esp Med Nucl Imagen Mol (Engl Ed), 2019, 38(6): 395−396[2020-10-21]. https://www.sciencedirect.com/science/article/abs/pii/S2253654X18302877?via%3Dihub. DOI: 10.1016/j.remn.2019.01.009. [6] Stölzel F, Lüer T, Löck S, et al. The prevalence of extramedullary acute myeloid leukemia detected by 18FDG-PET/CT: final results from the prospective PETAML trial[J]. Haematologica, 2020, 105(6): 1552−1558. DOI: 10.3324/haematol.2019.223032. [7] Arimoto MK, Nakamoto Y, Nakatani K, et al. Increased bone marrow uptake of 18F-FDG in leukemia patients: preliminary findings[J/OL]. Springerplus, 2015, 4: 521[2020-10-21]. https://springerplus.springeropen.com/articles/10.1186/s40064-015-1339-2. DOI: 10.1186/s40064-015-1339-2. [8] Alam MS, Fu L, Ren YY, et al. 18F-FDG super bone marrow uptake: a highly potent indicator for the malignant infiltration[J]. Medicine (Baltimore), 2016, 95(52): e5579. DOI: 10.1097/MD.0000000000005579. [9] 中华医学会血液学分会白血病淋巴瘤学组. 复发难治性急性髓系白血病中国诊疗指南(2017年版)[J]. 中华血液学杂志, 2017, 38(3): 183−184. DOI: 10.3760/cma.j.issn.0253-2727.2017.03.002.
Leukemia and Lymphoma Group, Branch of Hematology, Chinese Medical Association. The guidelines for diagnosis and treatment of acute myelogenous leukemia (relapse/refractory) in China (2017)[J]. Chin J Hematol, 2017, 38(3): 183−184. DOI: 10.3760/cma.j.issn.0253-2727.2017.03.002.[10] 中华医学会血液学分会干细胞应用学组. 中国异基因造血干细胞移植治疗血液系统疾病专家共识(Ⅲ)——急性移植物抗宿主病(2020年版)[J]. 中华血液学杂志, 2020, 41(7): 529−536. DOI: 10.3760/cma.j.issn.0253-2727.2020.07.001.
Stem Cell Application Group of Hematology Branch of Chinese Medical Association. Chinese consensus of allogeneic hematopoietic stem cell transplantation for hematological disease (Ⅲ)—acute graft-versus-host disease (2020)[J]. Chin J Hematol, 2020, 41(7): 529−536. DOI: 10.3760/cma.j.issn.0253-2727.2020.07.001.[11] Zhao ZX, Hu YE, Li JH, et al. Applications of PET in diagnosis and prognosis of leukemia[J]. Technol Cancer Res Treat, 2020, 19(19): 1−12. DOI: 10.1177/1533033820956993. [12] Zhang SX, Wang W, Kan Y, et al. Extramedullary infiltration of acute lymphoblastic leukemia in multiple organs on FDG PET/CT[J]. Clin Nucl Med, 2018, 43(3): 217−219. DOI: 10.1097/RLU.0000000000001964. [13] 李河北, 王茜, 赵赟赟, 等. 18F-FDG PET/CT对急性白血病髓内及髓外复发的诊断[J]. 中国医学影像学杂志, 2018, 26(2): 140−143, 147. DOI: 10.3969/j.issn.1005-5185.2018.02.015.
Li HB, Wang Q, Zhao YY, et al. Diagnosis of 18F-FDG PET/CT in intra and extramedullary relapse of acute leukemia[J]. Chin J Med Imaging, 2018, 26(2): 140−143, 147. DOI: 10.3969/j.issn.1005-5185.2018.02.015.[14] Wang XX, Huang XY, Zhang LJ, et al. Whole body FDG-PET/CT for the assessment of bone marrow infiltration in patients with newly diagnosed lymphoma[J]. Med Clín (Barc), 2020, 154(2): 61−65. DOI: 10.1016/j.medcli.2019.07.022. [15] Yousefi-Koma A, Shiravand Y, Qutbi M, et al. Diffuse skeletal uptake on 18F-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography scan in a patient with acute lymphoblastic leukemia: a typical superscan pattern resembling NaF positron emission tomography scan[J]. Indian J Nucl Med, 2019, 34(4): 326−328. DOI: 10.4103/ijnm.IJNM_106_19. [16] Sachpekidis C, Mai EK, Goldschmidt H, et al. 18F-FDG dynamic PET/CT in patients with multiple myeloma: patterns of tracer uptake and correlation with bone marrow plasma cell infiltration rate[J]. Clin Nucl Med, 2015, 40(6): e300−e307. DOI: 10.1097/RLU.0000000000000773. [17] Su K, Nakamoto Y, Nakatani K, et al. Diffuse homogeneous bone marrow uptake of FDG in patients with acute lymphoblastic leukemia[J]. Clin Nucl Med, 2013, 38(1): e33−e34. DOI: 10.1097/RLU.0b013e3182485277. [18] Yi C, Shi XC, Wang XY, et al. The alteration of 18F-FDG uptake in bone marrow after treatment with interleukin 11[J]. Clin Nucl Med, 2014, 39(10): 934−935. DOI: 10.1097/RLU.0000000000000491. [19] Chen YK, Yeh CL, Tsui CC, et al. F-18 FDG PET for evaluation of bone marrow involvement in non-Hodgkin lymphoma: a meta-analysis[J]. Clin Nucl Med, 2011, 36(7): 553−559. DOI: 10.1097/RLU.0b013e318217aeff. [20] Nakajo M, Jinnouchi S, Inoue H, et al. FDG PET findings of chronic myeloid leukemia in the chronic phase before and after treatment[J]. Clin Nucl Med, 2007, 32(10): 775−778. DOI: 10.1097/RLU.0b013e318148b467. [21] Janssens AM, Offner FC, Van Hove WZ, et al. Bone marrow necrosis[J]. Cancer, 2000, 88(8): 1769−1780. DOI: 10.1002/(SICI)1097-0142(20000415)88:8<1769::AID-CNCR3>3.0.CO;2-H. [22] 尹吉林, 王欣璐, 张金赫, 等. 18F-FDG PET/CT显像全身骨髓代谢弥漫增高原因分析[J]. 中华核医学杂志, 2011, 31(3): 151−154. DOI: 10.3760/cma.j.issn.0253-9780.2011.03.002.
Yin JL, Wang XL, Zhang JH, et al. Analysis on the reasons for diffuse 18F-FDG uptake by bone marrow using whole-body PET/CT[J]. Chin J Nucl Med, 2011, 31(3): 151−154. DOI: 10.3760/cma.j.issn.0253-9780.2011.03.002.[23] Adams HJA, Kwee TC, Fijnheer R, et al. Bone marrow FDG-PET/CT in Hodgkin lymphoma revisited: do imaging and pathology match?[J]. Ann Nucl Med, 2015, 29(2): 132−137. DOI: 10.1007/s12149-014-0920-z. [24] St-Pierre F, Broski S, Laplant B, et al. Maximizing FDG-PET/CT utility in staging of follicular lymphoma (FL): the role of spleen involvement and bone standardized uptake values[J]. Blood, 2019, 134(S1): S2811. DOI: 10.1182/blood-2019-131992. [25] Kaya Z, Akdemir OU, Atay OL, et al. Utility of 18-fluorodeoxyglucose positron emission tomography in children with relapsed/refractory leukemia[J]. Pediatr Hematol Oncol, 2018, 35(7/8): 393−406. DOI: 10.1080/08880018.2018.1557306.