Nonlymphocytic leukemia, acute: Abbreviated ANLL. More commonly called acute myeloid leukemia (AML). A quickly progressive malignant disease in which there are too many immature blood-forming cells in the blood and bone marrow. The cells being specifically over-produced are those destined to give rise to the granulocytes or monocytes, both types of white blood cells that fight infections. In AML, these blasts do not mature and so become too numerous. AML can occur in adults or children.
The early signs of AML may be similar to the flu or other common diseases with fever, (if there is an infection), weakness and fatigue, loss of weight and appetite, and aches and pains in the bones or joints. Other signs of AML may include tiny red spots in the skin, easy bruising and bleeding, frequent minor infections, and poor healing of minor cuts.
Blood tests are done to count the number of each of the different kinds of blood cells and see whether they are within normal ranges. In AML, the red blood cell levels may be low, causing anemia. Platelet levels may be low, causing bleeding and bruising and the white blood cell levels may be low, leading to infections.
A bone marrow biopsy or a bone marrow aspiration may be done if the results of the blood tests are abnormal. During a bone marrow biopsy, a hollow needle is inserted into the hip bone to remove a small amount of the marrow and bone for examination under a microscope. In a bone marrow aspirate, a small sample of liquid bone marrow is withdrawn through a syringe.
A lumbar puncture, or spinal tap, is not rountinely done to see if the disease has spread into the cerebrospinal fluid, which surrounds the central nervous system (CNS) -- the brain and spinal cord. Lumbar punctures are done for patients with symptoms of CNS involvement, which may include headache, lethargy, cranial nerve palsies, seizure, back pain, weakness, bladder dysfunction, or visual changes. Other key diagnostic tests may include flow cytometry (in which cells are passed through a laser beam for analysis), immunohistochemistry (using antibodies to distinguish between types of cancer cells), cytogenetics (to determine chromosome changes in cells), and molecular genetic studies (DNA and RNA tests of the cancer cells).
The primary treatment of AML is chemotherapy. Radiation therapy is less common; it may be used in certain cases. Bone marrow transplantation is coming into increasing use and when appropriate can increase the likelihood of cure.
There are two phases of treatment for AML. The first phase is called induction therapy. The purpose of induction therapy is to kill as many of the leukemia cells as possible and induce a remission, a state in which there is no visible evidence of disease and blood counts are normal. Patients may receive a combination of drugs during this phase including daunorubicin, idarubicin, or mitoxantrone plus cytarabine or etoposide. Once in remission with no signs of leukemia, patients enter a second phase of treatment.
The second phase of treatment is called post-remission therapy (or consolidation therapy). It is designed to kill any remaining leukemic cells. In post-remission therapy, patients may receive high doses of chemotherapy, designed to eliminate any remaining leukemic cells. Treatment may include a combination of cytarabine, daunorubicin, idarubicin, etoposide, or mitoxantrone.
There are a number of different subtypes of AML. AML was classified using an older system called the French American British (FAB) system. In this system, the subtypes of AML are grouped according to the particular cell line in which the disease developed. There are eight distinct types of AML, designated M0 through M7. Types M2 (myeloblastic leukemia with maturation) and M4 (myelomonocytic leukemia) each account for 25% of AML; M1 (myeloblastic leukemia, with few or no mature cells) accounts for 15%; M3 (promyelocytic leukemia) and M5 (monocytic leukemia) each account for 10% of cases; the other subtypes are rarely seen. AML is also classified according to the chromosomal abnormalities in the malignant cells.
There is also a newer classification system developed by the World Health Organization (WHO). This system has six main groups that are based on a combination of morphology, immunophenotypes, genetics and clinical features.
- AML with recurrent genetic abnormalities
- AML with myelodysplasia-related features
- Therapy-related AML and MDS
- AML, not otherwise specified
- Myeloid sarcoma
- Myeloid proliferations related to the Down syndrome
The treatment of the subtype of AML called acute promyelocytic leukemia (APL) differs from that for other forms of AML. (APL is M3 in the FAB system.) Without treatment, APL is the most malignant form of AML due to extensive bleeding. Treatment can be divided into three stages over one or two years of treatment: remission induction, consolidation and maintenance. In the past most APL patients were treated first with all-trans-retinoic acid (ATRA) plus chemotherapy including anthracycline drugs such as daunorubicin, idarubicin, mitoxantrone, and others). ATRA plus ATO (arsenice trioxide) is now the most common combination. which induces a complete response in 70% of cases and extends survival.The standard course of consolidation therapyis likely to include cytosine arabinoside (Ara-C)daunorubicin or and idarubicin plus ATRA. ATRA ATO may be continued during consolidation and maintenance in some patients. Arsenic trioxide has been used during induction therapy in patients who relapse. Bone marrow transplantation is considered for second remission patients.
Bone marrow transplantation is used to replace the bone marrow with healthy bone marrow. First healthy marrow is then taken from another person (a donor) whose tissue is the same as or almost the same as the patient's. The donor may be a twin (the best match), a brother or sister, or a person who is otherwise related or not related. Then the patient (recipient) has their bone marrow destroyed by high dose chemotherapy with or without radiation. The healthy marrow from the donor is given to the patient through a needle in the vein, and the marrow replaces the marrow that was destroyed. A bone marrow transplant using marrow from a relative or from a person who is not related is called an allogeneic bone marrow transplant. A greater chance for recovery occurs if the doctor chooses a hospital that does more than five bone marrow transplantations per year.