The basics about chronic myeloid leukemia
myeloid leukemia and What is acute myeloid leukemia?
aml leukemia
aml Leucemia mielógena aguda
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Chronic myeloid leukemia
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The basics of chronic myeloid leukemia
Management of chronic myeloid leukemias
Marrow transplant: multiple indications
Chronic myeloid leukemia (CML) is a rare cancer of the blood and bone marrow. There are 600 new cases each year, mainly after 50 years. Discover the basics about this disease that has recently benefited from new treatments.
Leukemia Bone marrow is the spongy tissue inside the bones. The stem cells of the marrow are at the origin of all the blood cells:
Red blood cells (erythrocytes) that carry oxygen to all organs and tissues;
White blood cells (leukocytes) that fight infections;
Platelets that allow the blood to clot to help stop bleeding when a blood vessel has been harmed.
Chronic myeloid leukemia is a cancer of the blood and marrow, which results in an excessive production of white blood cells, some of which remain immature. Their accumulation in the bone marrow and blood disrupts the functioning of other blood cells and causes the symptoms of chronic myeloid leukemia.
An acquired chromosomal anomaly
In France, 5,000 people suffer from this (15 to 20% of adult leukemias) and 600 new cases are diagnosed each year. Although CML can occur at any age, it affects mostly adults over the age of 50, with a slight male predominance. As the global population ages, the number of cases increases. However, this cancer remains rare, the proportion of people concerned in the world is 1 to 2 cases per 100,000 people. Apart from exposure to ionizing radiation, no cause has been found. There is thus no hereditary factor.
It is the first disease to have been associated with a chromosomal abnormality, the Philadelphia chromosome. "This abnormal chromosome results from an exchange of a small piece of genetic material between chromosomes 9 and 22, exchange giving rise to an abnormal gene, BCR-ABL, the origin of the protein Bcr-Abl" says Pr Mauricette Michallet, Hematologist at Edouard Herriot Hospital (Lyon) "This anomaly results in a permanent proliferation of marrow cells with dysregulation of cell death, which results in an excessive amount of white blood cells in the blood."
A chance discovery in 40% of cases
The onset of the disease is often devoid of symptoms. In 40% of cases, the discovery of the disease is thus fortuitous, during a routine blood test. The signs are intense fatigue and an increase in the volume of the spleen (splenomegaly). The diagnosis is then confirmed by a blood and marrow (myelogram) analysis with evidence of the Philadelphia chromosome.The disease evolves in three phases:
A chronic phase during which healthy white blood cells and platelets retain their functions. The passage in the blood of excess white blood cells (sometimes immature) does not give place for the moment to troublesome symptoms. In the absence of treatment, life expectancy without treatment of 3 to 5 years;
An accelerated phase during which the number of white blood cells and immature cells increase in the blood. The symptoms appear and the disease becomes more difficult to control. In the absence of treatment, the life expectancy is then 6 to 9 months;
A phase of acute blastic transformation during which more than a third of the blood cells and the marrow are immature (blasts). The disease is in an advanced stage and cancer cells can form tumors on the bones or lymph nodes. In the absence of treatment, life expectancy is 3 to 6 months.
Fortunately, more than 90% of patients are diagnosed during the chronic phase. And in recent years, treatments for chronic myeloid leukemia have experienced several revolutions, the main one is the advent of targeted therapies, drugs acting on the signals responsible for the uncontrolled growth of cancer cells. The leader in these molecules is imatinib (Glivec ®), which is now being offered as first-line therapy since it has been shown to be more effective and better tolerated than interferon. In subjects resistant to Glivec®, new molecules appear recently including dasatinib (Sprycel® marketed since 2006) and nilotinib currently tested. Finally, bone marrow transplantation is the only option to cure the disease. But it requires compatible donors and is accompanied by a mortality which is not negligible (of the order of 20%).
Management of chronic myeloid leukemias
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Chronic myeloid leukemia
SEE AS WELL
The basics about chronic myeloid leukemia
Management of chronic myeloid leukemias
Marrow transplant: multiple indications
Treatment of chronic myeloid leukemia (CML) is aimed at achieving complete remission, which means the disappearance of the signs of the disease. In just a few years, bone marrow transplantation and especially the emergence of targeted therapies have revolutionized the management.
Remission is when blood tests only detect bone marrow cells and healthy blood cells. When this goal is achieved, it is called a complete cytogenetic response. To do this, the management must eliminate leukemia cells, increase the life of patients and improve their quality of life.
Effective treatment in recent years
lmc treatment Management has long been fumbling with the use of arsenic in the 19th century or the irradiation of the spleen in the 1920s and some chemotherapy until the 1980s. "The first therapeutic revolution was the transplantation of the spinal cord. with the first patients cured, at the cost of significant toxicity Since then, progress has been made to reach more than 80% survival in the most favorable cases "says Dr. Philippe Rousselot, hemato-oncologist at André Hospital Mignot (The Chesnay).
Until 2000, the only treatments proposed were the bone marrow transplant, reserved for a minority of patients, or interferon alpha, used alone or in combination with chemotherapy. But the beginning of the 2000s was marked by a second therapeutic revolution.
Chronic myeloid leukemia: the revolution of targeted therapies
The second revolution took place in 2001 with the arrival of imatinib mesylate (Glivec®). An innovation that marks the advent of targeted therapies (we remember the famous cover of Time: "There is a new weapon in the war against cancer, and here are the bullets." This targeted treatment blocks the deregulation of a This molecule is used to improve the prognosis of the disease. "This treatment made it possible to obtain complete cytogenetic remissions in 80 to 85% of cases (against 15 to 20% for interferon with side effects). imatinib has gradually replaced the graft as a first-line treatment, and graft indications were then reserved for patients failing on imatinib, "confides Dr. Philippe Rousselot.
Glivec © is now the targeted reference therapy in CML and is routinely offered as first line because it is more effective, better tolerated and easier to administer (oral) than interferon. A five-year follow-up study confirms the long-lasting efficacy of this compound in patients (not pretreated) in the chronic phase of chronic myeloid leukemia. At five, the survival rate is even 90%! But sometimes, the subjects do not respond to treatment or develop resistance especially when the disease is in the acute transformation phase.
New targeted therapies take over
Young subjects who are resistant to Glivec ® may be offered a marrow transplant. But it requires compatible donors and is accompanied by a mortality which is not negligible (of the order of 20%).
Since the authorization of Glivec ®, other targeted therapies have been placed on the market. Today, these therapies are:
Dasatinib (Sprycel ®), marketed since 2006 by the Brystol-Myers Squibb laboratories, is a multi-site therapy because it acts on several oncogenic pathways. It is indicated in case of resistance or intolerance to imatinib.
Nilotinib (Tasigna ®) is a newer medicine marketed by Novartis Laboratories, which is already responsible for Glivec ®. Nilotinib is indicated for resistance or intolerance to imatinib.
Ponatinib (Iclusig ®), produced by Ariad Pharma, is indicated for use in dasatinib or nilotinib resistant cases.
These new therapeutic options have really revolutionized the management of chronic myeloid leukemia (CML). The advent of targeted therapies is now giving hope to patients who had not been able to benefit from first-generation drugs. Other targeted therapies are currently under development.
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