The first step in the successful treatment of a patient with acute myeloid leukemia (AML) is the attainment of a complete remission (CR), which is characterized by:
- Normal values for absolute neutrophil count (>1000/microL) and platelet count (>100,000/microL), and independence from red cell transfusion.
- A bone marrow biopsy that reveals no clusters or collections of blast cells. Extramedullary leukemia (eg, central nervous system or soft tissue involvement) must be absent.
- A bone marrow aspiration revealing normal maturation of all cellular components (ie, erythroid, granulocytic, and megakaryocytic series). There is no requirement for bone marrow cellularity.
- Less than 5 percent of blast cells present in the bone marrow, and none with a leukemic phenotype (eg, Auer rods). The persistence of dysplasia is worrisome as an indicator of residual AML, but has not been validated as a criterion for remission status.
Twenty to 30 percent of young adult patients and 50 percent of older adult patients with newly diagnosed AML will fail to attain a CR with intensive induction chemotherapy due to drug resistance or death. In addition, a percentage of patients who initially attain a CR will relapse. Treatment of the patient with AML who has failed to enter into CR or who has relapsed after attainment of CR will be reviewed here. The prognosis and initial treatment of the patient with AML are discussed separately. (See "Induction therapy for acute myeloid leukemia in younger adults" and "Treatment of acute myeloid leukemia in older adults" and "Prognosis of acute myeloid leukemia" and "Remission criteria in acute myeloid leukemia and monitoring for residual disease".)
EVALUATION FOR RELAPSE OR RESISTANCE
Definitions of relapse and refractory disease — Refractory (resistant) disease is defined by the failure to obtain a complete remission (CR) with induction therapy. This is also referred to as primary induction failure. In such cases, induction chemotherapy has failed to eradicate all detectable leukemia cells (less than 5 percent blasts) from the bone marrow and blood with subsequent restoration of normal hematopoiesis (greater than 25 percent marrow cellularity and normal peripheral blood counts). Patients who require two cycles of induction therapy to attain a first CR are not considered to have refractory disease. Depending upon post-remission therapy, they appear to have a similar prognosis to those who attain a CR with initial induction . Resistance to induction chemotherapy is closely associated with unfavorable cytogenetic features and poor overall outcome. (See "Remission criteria in acute myeloid leukemia and monitoring for residual disease".)
After attaining a CR with initial therapy, patients are followed at routine intervals to monitor for treatment-related complications and relapse. Relapsed disease describes the reappearance of leukemia cells in the bone marrow or peripheral blood or elsewhere in the body (other tissues/organs) after the attainment of a CR. As yet, the significance of the reappearance of AML detected only by polymerase chain reaction (PCR) analysis is uncertain. (See "Post-remission therapy for acute myeloid leukemia in younger adults", section on 'Monitoring for relapse' and "Remission criteria in acute myeloid leukemia and monitoring for residual disease", section on 'Use in non-APL AML'.)