Philadelphia-negative chronic myeloid leukemia is a slow-developing cancer of the bone marrow and blood in which the body produces an uncontrolled number of abnormal white blood cells. More than 90% of cases result from a cytogenetic aberration known as the Philadelphia chromosome (Philadelphia-positive chronic myeloid leukemia). For Philadelphia-negative chronic myeloid leukemia, the exact cause of the disease is not known. Although a variety of medications have been used in chronic myeloid leukemia, including myelosuppressive agents and interferon alpha, the tyrosine kinase inhibitor imatinib mesylate is currently the agent of choice, and other drugs in this category are playing increasingly important roles. However, allogeneic bone marrow transplantation is currently the only proven cure for chronic myeloid leukemia.
The list of signs and symptoms mentioned in various sources for Philadelphia-negative chronic myeloid leukemia includes the symptoms listed below:
• Weight loss
• Enlarged spleen
• Blood related abnormalities (Increased white blood cell count, decrease of red blood cells (anemia), decreased blood platelet count (thrombocytopenia))
• Susceptibility to infection
Undeveloped or immature white blood cells are called “blast” cells. When you have chronic myeloid leukemia, the bone marrow makes uncontrolled numbers of abnormal blast cells. These are the leukemia cells, or "blast" leukemia cells. They don't mature. They don't fight infections like regular mature white blood cells. These immature cells live longer, crowding out not only healthy white blood cells, but red blood cells and platelets as well. This leads then to the blood anomalies described in the symptoms section (low red blood cell and platelet count, high white blood cell count)
The exact cause of blood cancer is not known. Some types of blood cancer are due to spontaneous (not inherited) mutations in the genes that control production of specific types of blood cells. Immunocompromised people and people with autoimmune diseases have an increased risk of developing certain types of blood cancer.
In Philadelphia-positive chronic myeloid leukemia, a small part of the chromosomes 9 and 22 are mixed up, forming a shortened chromosome 22 (Philadelphia chromosome) and leading to the production of a malfunctioning tyrosine kinase, causing the disease.
In Philadelphia-negative chronic myeloid leukemia, the patients do not possess a shortened chromosome 22 (Philadelphia chromosome), but a proportion of them also possesses a chromosomal rearrangement within the chromosome 9.
Source: National cancer institute
•No known preventive strategies
The clinical manifestations of chronic myelogenous leukemia are insidious. The disease is often discovered incidentally in the chronic phase, when an elevated white blood cell count is revealed by a routine blood count or when an enlarged spleen is found on a general physical examination.
Historically, the median survival of patients with chronic myelogenous leukemia was 3-5 years from the time of diagnosis. Currently, patients with chronic myelogenous leukemia have a median survival of 5 or more years and a 5-year survival rate of 50-60%. The improvement has resulted from earlier diagnosis, improved therapy with interferon and bone marrow transplantation, and better supportive care.
In other sources, a follow-up on patients using imatinib published in the New England Journal of Medicine in 2006 showed an overall survival rate of 89% after five years. In 2011, an independent study performed in 832 CML patients worldwide reported that the group of patients who achieve a stable cytogenetic response with imatinib shows an overall survival rate of 95.2% after 8 years, which is similar to the rate in the general population. Only 1% of patients died because of leukemia progression.
The list of treatments mentioned in various sources for Philadelphia-negative chronic myeloid leukemia includes the following list.
•Tyrosinase kinase inhibitors (Imatinib, Dasatinib, and Nilotinib). Imatinib is the first line therapy for many people, and those unsuitable for stem cell transplantation
•Stem Cell transplantation
•Chemotherapy are used when tyrosine kinase inhibitors stop working or in combination with stem cell transplantation
•Interferon is used when other drugs don't work, or when they can't be used, such as in pregnant patients.