Page 374 - Textbook of Pathology, 6th Edition

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Figure 14.13 PBF findings in chronic myeloid leukaemia (CML).
SECTION II
1. Anaemia. Anaemia is usually of moderate degree and 2. Myeloid cells. The myeloid cells predominate in the
is normocytic normochromic in type. Occasional bone marrow with increased myeloid-erythroid ratio. The
normoblasts may be present. differential counts of myeloid cells in the marrow show
2. White blood cells. Characteristically, there is marked similar findings as seen in the peripheral blood with
leucocytosis (approximately 200,000/μl or more at the predominance of myelocytes.
time of presentation). The natural history of CML consists 3. Erythropoiesis. Erythropoiesis is normoblastic but there
of 3 phases—chronic, accelerated, and blastic. is reduction in erythropoietic cells.
Chronic phase of CML begins as a myeloproliferative 4. Megakaryocytes. Megakaryocytes are conspicuous but
disorder and consists of excessive proliferation of myeloid are usually smaller in size than normal.
cells of intermediate grade (i.e. myelocytes and 5. Cytogenetics. Cytogenetic studies on blood and bone
metamyelocytes) and mature segmented neutrophils. marrow cells show the characteristic chromosomal
Myeloblasts usually do not exceed 10% of cells in the abnormality called Philadelphia (Ph) chromosome seen
peripheral blood and bone marrow. An increase in the in 90-95% cases of CML. Ph chromosome is formed by
proportion of basophils up to 10% is a characteristic reciprocal balanced translocation between part of long arm
feature of CML. A rising basophilia is indicative of of chromosome 22 and part of long arm of chromosome
impending blastic transformation. An accelerated phase of 9{(t(9;22) (q34;11)} forming product of fusion gene, BCR/
CML is also described in which there is progressively ABL (see Fig. 14.11).
rising leucocytosis associated with thrombocytosis or
thrombocytopenia and splenomegaly. III. CYTOCHEMISTRY. The only significant finding on
Accelerated phase is defined as increasing degree of cytochemical stains is reduced scores of neutrophil alkaline
anaemia, blast count in blood or marrow between 10-20%, phosphatase (NAP) which helps to distinguish CML from
Haematology and Lymphoreticular Tissues
marrow basophils 20% or more, and platelet count falling myeloid leukaemoid reaction in which case NAP scores
below 1,00,000/μl. are elevated (see Fig. 14.10,B, and Table 14.3). However,
NAP scores in CML return to normal with successful
Blastic phase or blast crisis in CML fulfills the definition
of acute leukaemia in having blood or marrow blasts therapy, corticosteroid administration and in infections.
>20%. These blast cells may be myeloid, lymphoid, IV. OTHER INVESTIGATIONS. A few other accompa-
erythroid or undifferentiated and are established by nying findings are seen in CML:
morphology, cytochemistry, or immunophenotyping. 1. Elevated serum B and vitamin B binding capacity.
12
12
Myeloid blast crisis in CML is more common and 2. Elevated serum uric acid (hyperuricaemia).
resembles AML. However, unlike AML, Auer rods are
not seen in myeloblasts of CML in blast crisis. Treatment and Complications
3. Platelets. Platelet count may be normal but is raised in
about half the cases. Insight into molecular mechanism of CML has brought about
major changes in its therapy. The approach of modern
II. BONE MARROW EXAMINATION. Examination of therapy in CML is targetted at removal of all malignant clones
marrow aspiration yields the following results: of cells bearing BCR/ABL fusion protein, so that patient
1. Cellularity. Generally, there is hypercellularity with reverts back to prolonged non-clonal haematopoiesis i.e.
total or partial replacement of fat spaces by proliferating molecular remission from disease. This is achievable by the
myeloid cells. following approaches: