| ID | 152 |
|---|---|
| Name | CHRONIC MYELOID LEUKEMIA |
| Cause | |
| Signs Symptoms | |
| Diagnosis | |
| Investigations | Investigations: 1. Blood examination shows: Normochromic normocytic anemia, W.B.C. count is- 1-5 lacs/cmm. Myeloblasts usually number less than 10% of the total. Also an increase in eosinophils & basophils. Platelet count is increased initially but gradually diminised. 2. Bone-marrow cytology: Bone-marrow is often hypercellular mainly involving the myeloid series. The neutrophils of chronic myeloid leukemia are usually deficient of alkaline phosphatase. 3. Bone-marrow analysis: i. Chromosome analysis (to see presence of Ph chromosome), and ii. RNA analysis to demonstrate the presence of BCR ABL gene product. This is a confirmatory test for diagnosis |
| Management | |
| Introduction | Chronic myeloid leukemia (CML) is a disorder of proliferation which is unrestrained and excessive. The disease occurs mainly in the age-range of 30-80 years (peak at 55 years) and is equally common in males and females. Approximately 95% patients with CML have a chromosome abnormality known as the Philadelphia (Ph) chromosome. This is a shortened chromosome 22 resulting from a reciprocal translocation of material with chromosome 9. The break on chromosome 22 occurs in the breakpoint cluster region (BCR). The fragment from chromosome 9 that joins the BCR carries the ABL oncogene, which forms a chimeric gene with the remains of the BCR. This BCR ABL chimeric gene codes with tyrosine kinase activity play a causative role in the disease as an oncogene Natural history of Chronic myeloid leukemia (CML):2 CML disease has three phases: 1. Chronic phase (Early CML): This early phase of the disease does not behave like a malignant disease, responds well to treatment and is easily controlled. Bone marrow functions retain normal with white blood cells differentiable and neutrophils are able to combat infection. This phase typically lasts 3-5 years and on imatinib therapy the duration may be prolonged longer than 5 years in many patients. If the patient is not treated, the disease progresses to an accelerated and then acute blast phase i.e acute leukemia. 2. Accelerated phase (not always seen): In this phase disease control becomes more difficult. 3. Blast phase or crisis: In this phase, the disease transforms into an acute leukemia, either myeloid (70%) or lymphoblastic (30%). This phase is relatively refractory to treatment and majority patients die. Therefore, survival of the patient depends on the timing of development of blast crisis, which is indeed unpredictable. |
| History | |
| Etiology | |
| Clinical Features | Clinical features: 1. Onset is insidious. 2. Slowly advancing anemia with anorexia, loss of weight and sweating. 3. Gradual tiredness and lethergy. 4. Prominence of the abdomen and dragging discomfort in the left upper quadrant. 5. Epistaxis, bruising or other hemorrhages may occur. 6. Priapism and secondary gout may also occur. 7. The spleen is enlarged, it is firm, smooth & painless (if infarction then pain occurs), but lymph nodes are not usually involved. 8. The liver may also be enlarged (in 50% of patients). 9. Breathlessness. |
| Preventions | |
| Treatment | Treatment: Chronic phase: 1. General- good food & proper oral hygiene are important. 2. Chemotherapy: Imatinib (an inhibitor of BCR ABL tyrosine kinase activity)- the first-line drug in chronic phase CML therapy, producing complete cytogenic response with disappearance of the Ph chromosome in about 76% after 18 months of treatments. Patients are monitored by repeated bone marrow examination until in a complete cytogenic response, and then by 3 monthly real-time quantitative polymerage chain reaction (PCR) for BCR ABL mRNA transcripts in blood. Dasatinib or nilotinib (second-generation tyrosine kinase inhibitors)-these drugs can be considered as second option for those patients failing to respond or progress on imatinib. Or, Allogeneic bone marrow transplantation. Or, Classical cytotoxic drugs such as hydroxycarbamide (hydroxyurea) or interferon (interferon-alfa was considered first-line treatment before imatinib was developed). Accelerated phase and blast crisis: Imatinib- if the patient has not been received this drug, imatinib should be given.Or, Hydroxycarbamide (hydroxyurea) can be given as a single agent therapy. Or, Cytarabine, a low-dose therapy can also be tried. If the blast crisis and transformation occurs, the type of blast cells and type of transformed leukemia should be determined and decision of treatment should be taken accordingly. Other therapy- splenectomy has been shown to be of little value. |
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