Clinical and histological features retain their prognostic impact under interferon therapy of CML: A pilot study

Abstract

In 55 patients with Ph1+ CML under interferon (IFN) monotherapy, an immunohistochemical and morphometric study on pretreatment bone marrow biopsies was performed to evaluate the prognostic impact of clinical as well as histological disease features. For identification of megakaryocytes we used the PAS stain and CD61 to calculate the subfraction of precursors (pro- and megakaryoblasts). Demonstration of macrophages and their different subsets was carried out by PG-M1 (CD68) and the GSA-1 lectin. The erythroid precursors were stained by Ret40f (anti-glycophorin C). Density of argyrophilic (reticulin plus collagen) fibers was determined by applying Gomori's silver impregnation method. Clinical variables like state of hematological response to IFN administration, age, spleen and liver size, myeloblasts plus promyelocytes, basophils as well as basophils and eosinophils exerted a predictive capacity by univariate statistical analysis. However, when entering these factors into previously published risk models, i.e., the so-called Sokal score and its modifications, to assess subgroups with different survival patterns or relative risk groups, a clear-cut discrimination was not feasible. Bone marrow features of prognostic value consisted of megakaryocytes and their precursors, fibers, and pro- and erythroblasts. Only when including histological variables into a formerly reported Cox model, could a significant separation of patients into the different categories or relative risk groups be computated. In conclusion, the present data emphasize the prognostic impact of histological parameters to be considered in all clinical trials on CML.

Changing patterns of histological subgroups during therapy of Ph1+ chronic myelogenous leukaemia

“…By using morphometry and defined cut‐off points, 28% of our patients showed some degree of reticulin and collagen fibrosis which is in general agreement with other studies 6,21 . In line with previous data, 14–17 our results are confirmative, since they reveal an unfavourable prognosis of the myelofibrotic subgroup independently of applied therapeutic regimens.…”

“… 10–13 In this context myelofibrosis is of outstanding importance, because such patients were reported to show a significant worsening of survival. 14–17 When bone marrow histopathology in CML is categorized by semiquantitative grading systems, 18–20 patients with an increased number of megakaryocytes were found to evolve into reticulin and collagen fibrosis more frequently. 21 However, the underlying concept of these histological staging systems 18–20 which comprise a granulocytic or common, a megakaryocytic and a myelofibrotic subtype, has been repeatedly contested.…”

Apoptosis and proliferation (PCNA labelling) in CML—a comparative immunohistological study on bone marrow biopsies following interferon and busulfan therapy

“…2b and Table IV). Apoptosis should therefore be entered as an additional variable into the clinical 38 and morphological parameters 7,39,40 when trying to assess the prognostic impact on CML in patients with IFN administration.…”

Eosinophils and Basophils Carry the Fused BCR/ABL Gene in Chronic Myelogenous Leukemia: Direct Fluorescence in situ Hybridization Analysis on Blood Smears

“…Several studies reported the differences between leukemic basophils and normal basophils [14, 15, 16]. Although basophilia in CML is a well-known poor prognostic factor [17], we do not know much about the function of basophils in CML. We examined the basophils in CML directly for the presence of the BCR/ABL fusion and found that the basophils in CML are not only involved in the leukemic clone but also have a BCR/ABL fusion like other hemopoietic cells.…”