About Chronic Myelogenous Leukemia (CML)

A blood disorder hallmarked by the presence of a defective chromosome, the Philadelphia chromosome or Ph, which is a fusion of the 9 and 22 chromosomes. Molecularly, the defect is also seen as the fusion of the bcr-abl genes leading to a very active Abl Tyrosine kinase protein.

This abnormal activity results in the clinical manifestation in the Complete Blood Count or CBCs of abnormally high white cells, sometimes with enlargement of spleen, often discriminated from other acute leukemias by a very low peripheral leukocyte alkaline phosphatase or LAP score. It is discriminated from other chronic leukemias through the molecular detection of the bcr-abl defect by FISH or by PCR from peripheral blood or the Ph in a chromosomal or karyotyping analysis from a bone marrow aspirate sample.

There are three phases: Chronic and the advanced phases - Accelerated and Blast Crisis which is akin to the acute leukemias.

The prospects for CML is now very good with the advent of imatinib or Glivec®, a gold standard in the front line therapy of CML. The 5 year long term follow up of the IRIS trial shows only 7 per cent progressing to advanced state and decreasing severity of side effects with time. There is also an increase in attainment of cytogenetic and molecular responses over time. Hematologic remissions are common already at the three week mark. Although some in advanced cases, may observe prolonged periods of myelosuppresion and cytopenias, as the marrow is often thought to be zapped of the defective cells by the effective inhibition of bcr-abl, leaving few normal cells to repopulate and provide the blood cell requirements of the patient. With time, the marrow population improves and normalization of counts observed.

Indefinite use of imatinib is still recommended as some patients relapse on discontinuation even after CCyR or Complete Cytogenetic Remissions. Although there are indications that a subset population showing a high level of molecular remission (in a sensitivity of 1 defect out of a million cells) for two straight years may safely be off the drug with close monitoring by RT Q PCR, it is not yet clear why they can and why others cannot, hence discontinuation is not yet recommended.

Main objective of therapy is to decrease tumor load or Ph as soon as possible, and to keep the patient in the chronic phase
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About Gastro Intestinal Stromal Tumor (GIST)

GIST is a form of connective tissue cancer, or sarcoma. GISTs are therefore non-epithelial tumors, separate from more common forms of bowel cancer. 70% occur in the stomach, 20% in the small intestine and less than 10% in the esophagus. Small tumors are generally benign, especially when cell division rate is slow, but large tumors disseminate to the liver, omentum and peritoneal cavity. They rarely occur in other abdominal organs.

Signs and Symptoms
Patients present with trouble swallowing, gastrointestinal hemorrhage or metastases (mainly in the liver). Intestinal obstruction is rare, due to the tumor's outward pattern of growth. Often, there is a history of vague abdominal pain or discomfort, and the tumor has become rather large by time the diagnosis is made.

Generally, the definitive diagnosis is made with a biopsy, which can be obtained endoscopically, percutaneously with CT or ultrasound guidance or at the time of surgery.

Diagnosis
A biopsy sample will be investigated under the microscope. The histopathologist identifies the characteristics of GISTs (spindle cells in 70-80%, epitheloid aspect in 20-30%). Smaller tumors can usually be found to the muscularis propria layer of the intestinal wall. Large ones grow, mainly outward, from the bowel wall until the point where they outstrip their blood supply and necrose (die) on the inside, forming a cavity that may eventually come to communicate with the bowel lumen.

When GIST is suspected—as opposed to other causes for similar tumors—the histopathologist can use immunohistochemistry (specific antibodies that stain the molecule CD117 (also known as c-kit)—see below). Virtually all GISTs are CD117-positive. Other cells that show CD117 positivity are mast cells.

Some tumors of the stomach and small bowel referred to as leiomyosarcomas (malignant tumor of smooth muscle) would most likely be reclassified as GISTs today on the basis of immunohistochemical staining.

Therapy
Is best directed by physicians familiar with the disease. Such doctors, specifically surgeons and medical oncologists, are found at major cancer centers.


An organization consist of CML and GIST patients.