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Пульмонология, гематология (англ,рус)

AML with multilineage dysplasia. This category includes patients who have had a prior myelodysplastic syndrome (MDS) or myeloproliferative disease (MPD) that transforms into AML. This category of AML occurs most often in elderly patients and often has a worse prognosis.

AML and MDS, therapy-related. This category includes patients who have had prior chemotherapy and/or radiation and subsequently develop AML or MDS. These leukemias may be characterized by specific chromosomal abnormalities, and often carry a worse prognosis.

AML not otherwise categorized. Includes subtypes of AML that do not fall into the above categories.

Acute leukemias of ambiguous lineage. Acute leukemias of ambiguous lineage (also known as mixed phenotype or biphenotypic acute leukemia) occur when the leukemic cells can not be classified as either myeloid or lymphoid cells, or where both types of cells are present.

 

AML. Prognosis

nAcute myeloid leukemia is a curable disease; the chance of cure for a specific patient depends on a number of prognostic factors.

nThe single most important prognostic factor in AML is cytogenetics, or the chromosomal structure of the leukemic cell. About half of AML patients have "normal" cytogenetics; they fall into an intermediate risk group. A number of other cytogenetic abnormalities are known to associate with a poor prognosis and a high risk of relapse after treatment.

nAML which arises from a pre-existing myelodysplastic syndrome or myeloproliferative disease (so-called secondary AML) has a worse prognosis, as does treatment-related AML arising after chemotherapy for another previous malignancy. Both of these entities are associated with a high rate of unfavorable cytogenetic abnormalities.

nIn some studies, age >60 years and elevated lactate dehydrogenase level were also associated with poorer outcomes. As with most forms of cancer, performance status (i.e. the general physical condition and activity level of the patient) plays a major role in prognosis as well.

nCure rates in clinical trials have ranged from 20-45%; however, it should be noted that clinical trials often include only younger patients and those able to tolerate aggressive therapies. The overall cure rate for all patients with AML (including the elderly and those unable to tolerate aggressive therapy) is likely lower.

AML. Treatment

nTreatment of AML consists primarily of chemotherapy, and is divided into two phases:

 induction

postremission (or consolidation) therapy.

The goal of induction therapy is to achieve a complete remission by reducing the amount of leukemic cells to an undetectable level;

the goal of consolidation therapy is to eliminate any residual undetectable disease and achieve a cure.

 

Chronic myelogenous leukemia (CML)

nis a form of chronic leukemia characterized by increased and unregulated clonal production of predominantly myeloid cells in the bone marrow.

nCML is a myeloproliferative disease associated with a characteristic chromosomal translocation called the Philadelphia chromosome.

nHistorically, it has been treated with chemotherapy, interferon and bone marrow transplantation, although targeted therapies introduced at the beginning of the 21st century have radically changed the management of CML.

The Philadelphia chromosome as seen by metaphase FISH

CML. Essentials of diagnosis

nStrikingly elevated white blood count

nMarkedly left-shifted myeloid series but with a low percentage of promyelocytes and blasts

nPresence of Philadelphia chromosome or bcr-abl gene

Oil immersion field demonstrating myeloid cells of all degrees of maturity

This high-power microscopic view of a blood smear from a person with classical CML shows predominantly normal-appearing cells with intermediate maturity

 

 

CML. Phases

nCML is often divided into three phases based on clinical characteristics and laboratory findings. In the absence of intervention, CML typically begins in the chronic phase, and over the course of several years progresses to an accelerated phase and ultimately to a blast crisis. Blast crisis is the terminal phase of CML and clinically behaves like an acute leukemia. One of the drivers of the progression from chronic phase through acceleration and blast crisis is the acquisition of new chromosomal abnormalities (in addition to the Philadelphia chromosome). Some patients may already be in the accelerated phase or blast crisis by the time they are diagnosed.

 

Low power view showing marked hypercellularity with a broad-spectrum of myeloid and erythroid cell types and marked myeloid hyperplasia

 

CML. Treatment

nGeneral strategies for management include a variety of options:

nLeukapheresis, also known as a peripheral blood stem cell transplant, with stem cell cryopreservation (frozen storage) prior to any other treatment. The patient's blood is passed through a machine that removes the stem cells and then returns the blood to the patient. Leukapheresis usually takes 3 or 4 hours to complete. The stem cells may or may not be treated with drugs to kill any cancer cells. The stem cells then are stored until they are transplanted back into the patient.

CML. Treatment

nHLA (human leukocyte antigen) typing of all patients under age 60, as well as typing of siblings, parents, and children, if available. This procedure will determine whether a compatible donor is available for stem cell transplantation.

nPre-treatment fertility measures (e.g., cryopreservation of semen prior to treatment; completion of a pregnancy prior to treatment) in young patients who have not completed their families.

nInterferon-alpha (INF-a) therapy

nChemotherapy with drugs such as hydroxyurea (Hydrea®), busulfan (Myleran®) or imatinib mesylate (Gleevec™).

 

In general, CML treatment options are divided into 2 groups:

                   - those that do not increase survival

                   - and those that do.

 

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