acute myeloid leuke | Acute myeloid leukemia (LMA) (Acute myeloid leukemia)

Acute myeloid leukemia (LMA)
(Acute myeloid leukemia)

In acute myeloid leukemia (LMA), malignant transformation and uncontrolled proliferation of a hematopoietic progenitor cell leads to the infiltration of the normal marrow by leukemic malignant cells and their potential passage in number High in peripheral blood. Symptoms include asthenia, paleness, bruises and hemorrhages, fever, or infection; Symptoms related to infiltration leukemia hematopoiesis are present in about 5% of the cases (often skin manifestations). Examination of the blood smear and bone marrow confirms the diagnosis. The treatment includes induction chemotherapy to obtain complete remission and consolidation treatment (with or without hematopoietic stem cell grafting) to prevent relapse.

For a general review of acute leukemias general review of acute leukemias.

The incidence of acute myeloid leukemia (LMA) increases with age; It is the most frequent form of acute leukemia in adults, with a median of age around 50 years. Acute myeloid leukemia (LMA) may be secondary to chemotherapy or radiation therapy for another type of cancer. Secondary acute myeloid leukemia (LMA) is difficult to treat by chemotherapy alone.

Acute myeloid leukemias (LMA) are classified into many subtypes defined by morphology, immunophenotyping, and cytochemistry of leukemic cells. Five categories were described, depending on the predominant cell type,

Myeloid

Monocytic myeloid

Monocytic

Erythroid

Mégacaryocytique

Acute promyelocytic leukemia is a specific subtype, representing 10-15% of acute myeloid leukemia (LMA), affecting a rather young age group (median age 31 years), with a higher incidence in some (Hispanic) populations, Which a coagulopathy is often the sign of presentation.

Acute leukemia promyelocytic acute leukemia promyelocytic acute promyelocytic leukemia
By the publisher's permission. According to Chang K, Forman S. In Atlas of clinical Hematology. Edited by JO Armitage. Philadelphia, Current Medicine, 2004.

Acute non-maturing myeloid leukemia acute myeloid leukemia without maturation acute myeloid leukemia
By the publisher's permission. According to Chang K, Forman S. In Atlas of clinical Hematology. Edited by JO Armitage. Philadelphia, Current Medicine, 2004.

Prognosis
Remission rates range from 50 to 85%. Long-term survival without relapse affects between 20 and 40% of the subjects and increases between 40 and 50% in the young person treated with intensive chemotherapy or stem cell grafting.

Prognostic factors are essential for the choice of therapeutic protocol and its intensity; In the presence of bad prognosis, usually the treatment is more intensive, because the potential benefits justify the increase of the risk of toxicity of the treatment. An important prognostic factor is the karyotype of the Leukemia cell. The specific chromosomal rearrangements of the various forms of acute myeloid leukemia (LMA) have a major influence on the results of treatments. Three clinical groups were identified: favorable, intermediate and unfavourable. Patients with cytogenetic signs T (8; 21), T (15; 17), and INV (16) typically respond favourably to treatment, have good remission time and longer survival. Patients with a normal karyotype are an intermediate risk group and patients with a deletion of chromosome 5 or 7, a Down syndrome, or a karyotype with > 3 anomalies represent the unfavourable risk group. Molecular genetic anomalies are increasingly important in refining the treatment and prognosis of acute myeloid leukemia (LMA). Mutations in the FLT3 kinase gene in particular are of a less favorable prognosis and are targets for further treatment. Other bad prognosis include an advanced age, a history of Myelodysplasia, a secondary leukemia, an initial leukocytosis, and the absence of Auer bodies. Except in the case of acute promyélocytaires leukemias, the FAB or who classifications alone do not predict the response to treatment.

Treatment

Chemotherapy (induction and consolidation)

Sometimes, hematopoietic stem cell transplant

Induction treatment

The initial treatment attempts to induce remission and differs most from that of acute lymphoblastic leukemia (LAL) in that acute myeloid leukemia (LMA) responds to fewer medications. Standard induction treatment includes the combination of cytarabine in continuous IV or high doses for 5 to 7 J; Daunorubicin or idarubicin administered by IV for 3 days during the same period. Some protocols also include 6-thioguanine, etoposide, vincristine, and prednisone, but the interest of these drugs has not been demonstrated. Treatment usually results in deep aplasia, with the risk of infection and hemorrhage. There is a significant latency before the marrow is healed. During this period, preventive measures and supportive care are needed (general review of acute leukemias: supportive care).

In acute promyelocytic leukemia and some other cases of acute myeloid leukemia (LMA), disseminated intravascular coagulation (DLC) may be present in the diagnosis of leukemia and worsen during initiation of treatment, lysis of Leukemic cells releasing procoagulant substances. In acute promyelocytic leukemia with translocation T (15; 17), All-trans-retinoic acid (Tretinoin) corrects the DLC in 2 to 5 days; associated with daunorubicin or idarubicin, this treatment can induce remission in 80 to 90% of patients and allow long-term survival in 65 to 70% of cases. Arsenic trioxide is also very effective in the treatment of acute promyélocytaires leukemias.

Consolidation processing

After obtaining a complete remission, the treatment usually involves a phase new phase of intensification using either the same or other drugs as those used during induction. Therapeutic protocols using high doses of cytarabine can prolong the duration of the complete remission, especially in consolidation in patients of < 60 years. CNS prophylaxis is not usually carried out in adults, as CNS leukemia impairment is an infrequent complication. In patients with acute myeloid leukemia (LMA) who have had consolidation, maintenance treatment has not shown any interest.

Relapse

Patients who have not responded to treatment and young patients in remission but who are at high risk of relapse (often identified by high-risk molecular or chromosomal abnormalities) may benefit from high-dose chemotherapy and Of a stem cell transplant. Isolated extramédullaires relapses are rare. In the case of relapse, new chemotherapy in patients who cannot receive a hematopoietic stem cell transplant is often less effective and poorly tolerated. A new cycle of chemotherapy is on the other hand more effective in young patients and in those whose first remission duration is 1 year.

Key Points

Acute myeloid leukemia (LMA) is the most common acute leukemia in adults.

There are a number of subtypes, usually involving very immature myeloid cells.

Chromosomal anomalies are common and have prognostic and therapeutic implications.

Chemotherapy often extends life.

Stem cell transplantation may be useful in patients who do not respond to treatment and in young patients.