Page 375 - Textbook of Pathology, 6th Edition

1. Imatinib oral therapy: The basic principle underlying slowly progressive course. Clinical features are the result of 359
imatinib oral treatment is to competitively inhibit ATP hyperviscosity, hypervolaemia, hypermetabolism and
binding site of the ABL kinase, which in turn, inhibits signal decreased cerebral perfusion. These are as under:
transduction BCR/ABL fusion protein. Imatinib induces 1. Headache, vertigo, tinnitus, visual alterations syncope
apoptosis in BCR/ABL-positive cells and thus eliminates or even coma.
them. Imatinib is found more effective in newly diagnosed 2. Increased risk of thrombosis due to accelerated athero-
cases of CML. Complete haematologic remission is achieved sclerosis.
for 18 months in 97% cases treated with imatinib.
3. Increased risk of haemorrhages due to increased blood
2. Allogenic bone marrow (stem cell) transplantation. volume and intrinsic platelet dysfunction e.g. epistaxis,
Although this treatment modality offers proven cure, it is peptic ulcer disease.
complicated with mortality due to procedure and 4. Splenomegaly producing abdominal fullness.
development of post-transplant graft-versus-host disease 5. Pruritus, especially after a bath.
(GVHD) and, therefore, post-transplant immunosuppressive
treatment has to be continued. 6. Increased risk of urate stones and gout due to
hyperuricaemia.
3. Interferon-α. Prior to imatinib and allogenic trans-
plantation, chronic phase of CML used to be treated with Laboratory Findings CHAPTER 14
interferon-α was the drug of choice.
PV is diagnosed by the following haematologic findings:
4. Chemotherapy. Chemotherapeutic agents are used in
treatment of CML for lowering the total population of WBCs. 1. Raised haemoglobin concentration (above 17.5 g/dl in
These include use of busulfan, cyclophosphamide males and 15.5 g/dl in females).
(melphalan) and hydroxyurea. 2. Erythrocytosis (above 6 million/μl in males and
5.5 million/μl in females).
5. Others. Besides above, other forms of treatment include
splenic irradiation, splenectomy and leucopheresis. 3. Haematocrit (PCV) above 55% in males and above 47%
The most common cause of death (in 80% cases) in CML in females.
is disease acceleration and blastic transformation. 4. Mild to moderate leucocytosis (15,000-25,000/μl) with
basophilia and raised neutrophil alkaline phosphatase
POLYCYTHAEMIA VERA scores.
Definition and Pathophysiology 5. Thrombocytosis with defective platelet function.
6. Bone marrow examination reveals erythroid hyper-
Polycythaemia vera (PV) is a clonal disorder characterised plasia or panhyperplasia.
by increased production of all myeloid elements resulting in
pancytosis (i.e increased red cells, granulocytes, platelets) in 7. Cytogenetic abnormalities such as 20q, trisomy 8 and
the absence of any recognisable cause. The term 9p are found in 30% cases of PV. Disorders of Leucocytes and Lymphoreticular Tissues
‘polycythaemia vera’ or ‘polycythaemia rubra vera’ is used 8. In PV, unlike secondary polycythaemia, erythropoietin
for primary or idiopathic polycythaemia only and is the most levels in serum and urine are reduced.
common of all the myeloproliferative disorders. Secondary
polycythaemia or erythrocytosis, on the other hand, may occur Treatment and Complications
secondary to several causes e.g. high altitude, cardiovascular
disease, pulmonary disease with alveolar hypoventilation, Since PV runs an indolent course, therapy is aimed at
heavy smoking, inappropriate increase in erythropoietin maintaining normal blood counts and relieve the patient of
(renal cell carcinoma, hydronephrosis, hepatocellular carci- symptoms.
noma, cerebellar haemangioblastoma, massive uterine 1. Phlebotomy (venesection) by blood letting is done at regular
leiomyoma); sometimes relative or spurious polycythaemia interval to reduce total blood cell mass and to induce a state
may result from plasma loss such as in burns and in of iron deficiency.
dehydration from vomiting or water deprivation. None of 2. Anticoagulant therapy is adminstered in case thrombosis
the secondary causes of polycythaemia is associated with has occurred.
splenic enlargement or increased leucocytes and platelets 3. Chemotherapy may be indicated to induce myelosuppresion.
which are typical of PV. 4. Hyperuricaemia is treated with uricosuric drugs.
The exact etiology of PV is not known but about a third
of cases show inconsistent and varied chromosomal 5. Interferon-α is associated with good results because it
abnormalities such as 20q, trisomy 8 and 9p. Major reduces JAK2 expression in these patients which is the
pathogenetic mechanism is a tyrosine kinase JAK2 mutation underlying cytogenetic abnormality.
which removes the autoinhibitory control and activates the Patients receiving phlebotomy alone may survive for 10-
kinases. 12 years. About 25% patients progress to myelofibrosis. A
small proportion of patients develop secondary haematologic
Clinical Features malignancies such as AML, non-Hodgkin’s lymphoma and
PV is a disease of late middle life and is slightly more multiple myeloma. Major complication and cause of death
common in males. The disease generally runs a chronic but in PV is vascular thrombosis.