oF eam amt ov ~e 25 a Fig. 2.04 Crone myeio eukaoma, BCR-ABLI-postive eccalrted pate). A Bone marc blosy specimen shows aeas of ella depletan and prominence of sal rhogskarocjtes. The ening appearance ofthe celica ‘wth aoeasiora lasts. © An rcrease in bliss sprees Moderate to marked reticulin fibrosis, ‘which correlates with increased numbers of megakaryocytes and may be assoc ated with an enlarged spleen, has been reported in 30-40% of biopsies at diag- nosis (480,495,1929,3962}. although the presence of fibrosis at the time of diag- nosis was reported to be associated with ‘2 worse outcome in the pre-TKI era, it reportedly has no substantial impact on prognosis in patients treated with TKls 1926 1932}. Splenic enlargement in CP is due to in filtration of the red pulp cords by mature and immature granulocytes. A similar infitrate can be seen in hepatic sinuses ‘and portal areas, Fig.205 Chrone mls leukaemia, BCR-ABLI-posive, melas ba sed by sine Disease phases Disease progression: accelerated phase and blast phase Recognition of disease progression is Important for treatment and prognostic ‘purposes, but the clinical and morpho- logical boundaries between CP, AP, and BBP are not always sharp, and the param- eters used to define them differ between investigators. These categories were of substantial prognostic importance in the pre-TKI era, when effective treatment Without allogeneic transplant was_not available, but the effectiveness of TKis has further blurred the lines between these phases of CML. For example, some studies show that newly diagnosed patients who initially present in AP may have similar outcornes, when treated with Tkls, as those of patients with newly dia. ‘gnosed CP [2939,3324). In contrast, AP cote wits toed cls ar ass. and C Sheets of lst n tha bone marow biopsy. D Myeoperocase (MPO) immunchistacomisry proving he myeloid ogi ofthe bess 32 Myeloproliferative neoplasms: nundering relic fbres. B Besopisaccouted for mre han 20% fre WBCS in his cae, the cps ith CD34 an asprate could ot be bind defo creases tui bos. disease that develops during TK! therapy has a poor outcome. Furthermore, gene expression studies of CP, AP, and BP suggest that progression of CP to AP andjor BP is more consistent with a two- step process, with new gene expression profiles occurring early in AP (or late in CP), betore the accumulation of blasts and other features offen used to define AAP (9277). BP continues to have a very poor outcome, even with TKI therapy {1601}. Death occurs due to bleeding or infectious complications, as normal hae- ‘matopoiesis is increasingly disrupted by the malignant calls. In BP, the increase in blasts not only indicates a loss of re- sponse to therapy, but also signifies that the disease has acquired characteristics of acute leukaemia, Accelerated phase In the original 4th edition of the classif- ‘cation, it was recommended that the clagnosis of AP be made if any of the folowing parameters were present: (1) a persistent or increasing high WBC count (> 10 x 10°/L) anajor persistent or increasing splenomegaly, unresponsive to therapy; (2) persistent thrombocyto- sis (> 1000 x 10%L), unresponsive to therapy: (3) persistent thrombocytopenia (< 100 x 10°/L), unrelated to therapy; (4) evidence of clonal cytogenetic evolu- tion, defined by cells harbouring the Ph ‘chromosome and additional cyiogenetic ‘changes; (5) >20% basophils in the pe- ripheral blood: and (6) 10-19% biasts in the peripheral blood andjor bone mat- row, In addition, large clusters or sheets of small, abnormal megakaryocytes as- sociated with marked reticulin or colla- {gen fibrosis were considered to be pre- sumptive evidence of AP, particularly it ‘accompanied by any of the haematologi ‘cal parameters listed above. Although ‘ther defining criteria for AP have been