Independent Prognostic Significance of Cytogenetics, Immunophenotype, Tumor Burden, and Age in Acute Myeloid Leukemia. Analysis of Patients Treated within PALG 1999 Prospective, Randomized Study.

Acute myeloid leukemia (AML) refers to a group of distinct diseases that differ with regard to their genetic charakteristics, clinical features, response to therapy, and prognosis. Patients require precise initial evaluation of risk factors including cytogenetics and immunophenotype to plan an optimal treatment program.

In this study we analyzed impact of cytogenetics, cell surface marker expression and clinical features on complete remission (CR) rate, leukemia-free survival (LFS) and overall survival (OS).

Four-hundred-forty-five AML patients, aged 18–60 years, treated within a multicentre study by the Polish Adult Leukemia Group (PALG 1999 Study) between 1999–2002 were included in the analysis. Induction therapy consisted of daunorubicine+cytarabine+/−cladribine, consolidation included two courses containing high-dose cytarabine (HAM, HD-AraC+/−cladribine).

In multivariate analysis the following factors were found to be associated with poor outcome:

1. For CR rate: unfavorable cytogenetics according to CALGB criteria (RR=5,5, p=0,00001), WBC ≥50 x10⁹/L at diagnosis (RR=3,3, p=0,00007), and age ≥50 (RR=1,9, p=0,021).

2. For LFS: unfavorable cytogenetics (RR=1,7, p=0,026), and lack of CD117 expression on leukemic cells (RR=1,8, p=0,026).

3. For OS: unfavorable cytogenetics (RR=1,8, p=0,00002), WBC ≥50 x10⁹/L at diagnosis (RR=1,1, p=0,0007), age ≥50 (RR=1,6, p=0,002), and lack of CD33 expression on leukemic cells (RR=1,7, p=0,014).

CONCLUSIONS: In this study we demonstrated that besides cytogenetics, other factors including particular phenotypic features, as well as initial tumor burden, and age independently influence outcome of AML patients. Results of the analysis provide practical information that could be taken into account when planning individualized treatment including indications for high-dose therapy followed by bone marrow transplantation.