Schwarz J, Mikulenková D, Cermáková M, Polanská V, Michalová K, Marinov I, Campr V, Ransdorfová S, Marková J, Pavlistová L, Brezinová J, Sajdová J, Sponerová D, Volková Z, Benesová K, Cermák J, Vítek A, Cetkovský P
Institute of Hematology and Blood Transfusion, CZ-128 Prague, Czech Republic.
Neoplasma. 2006;53(3):219-25.
Morphological examination is the routine first step in the diagnosis of hematological malignancies, including chronic lymphocytic leukemia (CLL). Atypical cell morphology according to the FAB criteria is known to herald disease progression. Several years ago, it was proposed that FAB morphology at diagnosis had a considerable prognostic impact. However, this proposal has not been widely adopted in practice. Thus we questioned the prognostic value of the morphological examination, which was performed retrospectively in 88 patients out of our 110 institutional registry patients (70 males and 40 females, median age 57 yrs) with CLL at diagnosis. We related the results to the more modern prognostic markers. Atypical FAB morphology was shown to correlate with IgVH gene mutation status, trisomy of chromosome 12 and deletion of 17p detected either by conventional G-banding or by fluorescence in situ hybridization (FISH) analysis. The correlation of FAB morphology with CD38 antigen expression or with the histopathological pattern of bone marrow infiltration was not significant. Overall survival (OS) data were available for 84 morphologically examined patients. The patients with atypical morphology (64 patients) had a significantly shorter OS (103 months) than the 20 patients presenting with typical CLL morphology (237 months; p=0.03). Only the mutation status of IgVH genes correlated more closely with OS (p=0.002). Of note, there was no leukemia-related death within "unmutated" cases who had typical FAB morphology (p=0.14), and vice versa, the mutation status had a significant prognostic impact within the morphologically atypical cases (p=0.01). Thus FAB morphology and the mutation status may yield complementary prognostic information. OS was affected both by the presence of cytogenetic aberrations (p=0.03) - most adversely by deletions of 17p and 11q, and by CD38 expression (p=0.003). We conclude that careful examination of peripheral blood smears according to FAB is a simple, cheap and valuable tool in the first-line assessment of prognosis of CLL patients and should not be overlooked even in 3rd millennium when more sophisticated prognostic markers are at hand. This ought to be confirmed in larger prospective studies with multivariate analysis of data.
形态学检查是诊断血液系统恶性肿瘤（包括慢性淋巴细胞白血病（CLL））的常规首要步骤。已知符合FAB标准的非典型细胞形态预示疾病进展。数年前，有人提出诊断时的FAB形态具有相当大的预后影响。然而，这一观点在实践中尚未被广泛采用。因此，我们对形态学检查的预后价值提出质疑，对我们机构登记的110例诊断为CLL的患者中的88例（70例男性和40例女性，中位年龄57岁）进行了回顾性形态学检查。我们将结果与更现代的预后标志物进行关联。结果显示，非典型FAB形态与IgVH基因突变状态、12号染色体三体以及通过传统G显带或荧光原位杂交（FISH）分析检测到的17p缺失相关。FAB形态与CD38抗原表达或骨髓浸润的组织病理学模式之间的相关性不显著。84例接受形态学检查的患者有总生存（OS）数据。非典型形态的患者（64例）的OS（103个月）明显短于20例呈现典型CLL形态的患者（237个月；p = 0.03）。只有IgVH基因的突变状态与OS的相关性更密切（p = 0.002）。值得注意的是，具有典型FAB形态的“未突变”病例中无白血病相关死亡（p = 0.14），反之亦然，在形态学非典型病例中，突变状态具有显著的预后影响（p = 0.01）。因此，FAB形态和突变状态可能产生互补的预后信息。OS受细胞遗传学异常的影响（p = 0.03）——最不利的是17p和11q缺失，以及受CD38表达的影响（p = 0.003）。我们得出结论，根据FAB仔细检查外周血涂片是一线评估CLL患者预后的简单、廉价且有价值的工具，即使在拥有更复杂预后标志物的第三个千年也不应被忽视。这应该在更大规模的前瞻性研究及数据多变量分析中得到证实。
