Thiele J, Kvasnicka H M, Schmitt-Gräff A, Hülsemann R, Diehl V
Institute of Pathology, University of Cologne, Cologne, Germany.
Histol Histopathol. 2004 Jan;19(1):239-50. doi: 10.14670/HH-19.239.
In chronic myeloproliferative disorders (CMPDs) a conflict of opinion exists regarding therapy-induced bone marrow (BM) changes and the evolution of myelofibrosis during the lengthy course of the disease. For a more elaborate study of these features chronic idiopathic myelofibrosis (IMF) seems to be a most suitable condition. Therefore this review is focused on this CMPD and amongst other findings analyzes data from a series of 340 patients with a long follow-up including 893 biopsies (median interval of 32 months). The ensuing results were compared with those communicated in the relevant literature. In addition to a control group of 153 patients with IMF who received only symptomatic treatment, therapy groups included busulfan, hydroxyurea, interferon and various combinations. In all groups hypoplasia of a varying degree was a frequent finding (6%) and often accompanied by a patchy arrangement of hematopoiesis. Most conspicuous was a gelatinous edema showing a tendency to develop a discrete reticulin fibrosis (scleredema). Aplasia developed in 7.7% of patients, usually at terminal stages of the disease independently of treatment. Minimal to moderate maturation defects of hematopoiesis involved especially megakaryocytes and erythroid precursors, but overt myelodysplastic features were most prominent following hydroxyurea and busulfan therapy. Acceleration and blastic crisis were characterized not only by increasing dysplastic changes, but also by the appearance of blasts including CD34+ cells. Semiquantitative grading of the fiber content revealed that 183 patients (54%) without or with moderate fibrosis at the beginning showed a significant progression and therefore contrasted with the 66 patients with a stable state. Following this calculation no relevant differences in the evolution of myelofibrosis were evident in the various therapy groups especially not following interferon treatment. In a few patients a regression was found which was accompanied by a severe hypoplasia or aplasia compatible with a myelo-ablative effect. In conclusion, peculiar BM changes, in particular conspicuously expressed myelodysplastic features are consistent with therapy-related lesions. Development of myelofibrosis in IMF is obviously due to disease progression unrelated to stage at diagnosis and not significantly influenced by treatment modalities.
在慢性骨髓增殖性疾病（CMPDs）中，对于治疗引起的骨髓（BM）变化以及疾病漫长病程中骨髓纤维化的演变存在意见分歧。为了更详尽地研究这些特征，慢性特发性骨髓纤维化（IMF）似乎是最合适的病症。因此，本综述聚焦于这种CMPD，并在其他研究结果中分析了来自340例患者的系列数据，这些患者进行了长期随访，包括893次活检（中位间隔时间为32个月）。随后将结果与相关文献中报道的结果进行了比较。除了153例仅接受对症治疗的IMF患者组成的对照组外，治疗组包括白消安、羟基脲、干扰素以及各种联合治疗。在所有组中，不同程度的骨髓增生低下是常见表现（6%），且常伴有造血的斑片状分布。最显著的是出现胶样水肿，有发展为离散性网状纤维纤维化（硬化性水肿）的倾向。7.7%的患者出现再生障碍，通常在疾病终末期，与治疗无关。造血的轻度至中度成熟缺陷尤其累及巨核细胞和红系前体细胞，但明显的骨髓增生异常特征在羟基脲和白消安治疗后最为突出。加速期和急变期不仅以发育异常变化增加为特征，还以包括CD34+细胞在内的原始细胞出现为特征。纤维含量的半定量分级显示，183例（54%）开始时无纤维化或有中度纤维化的患者显示出显著进展，因此与66例病情稳定的患者形成对比。经此计算，在各个治疗组中，尤其是干扰素治疗后，骨髓纤维化的演变没有明显差异。在少数患者中发现有消退情况，同时伴有与清髓效应相符的严重骨髓增生低下或再生障碍。总之，特殊的骨髓变化，特别是明显表现出的骨髓增生异常特征与治疗相关病变一致。IMF中骨髓纤维化的发展显然是由于疾病进展，与诊断阶段无关，且不受治疗方式的显著影响。
