Multivariate analysis of prognostic factors in patients with refractory and relapsed acute myeloid leukemia undergoing sequential high-dose cytosine arabinoside and mitoxantrone (S-HAM) salvage therapy: relevance of cytogenetic abnormalities

Abstract

To improve the basis for the stratification of patients with refractory and relapsed acute myeloid leukemia (AML) univariate and multivariate analyses of prognostic factors were performed in 254 patients (median age 50 years, range 18-74) undergoing S-HAM salvage chemotherapy during two consecutive prospective trials of the German AML Cooperative Group. In a multivariate analysis, duration of the first complete remission (CR) was the only factor associated with time to treatment failure (P = 0.0223). Disease-free survival was influenced by a short duration of the first CR of less than 6 months (P = 0.0001), WBC (P = 0.0018), blast count (P = 0.0037), and neutrophil count (P = 0.0119). The achievement of CR was related to the hemoglobin level only (P = 0.0457), the early death rate was related to age only (P = 0.0109), and survival was related to the bilirubin level only (P = 0.0166). In the subgroup of 104 patients in whom additional karyotype analyses were performed prior to first-line therapy unfavorable chromosome abnormalities were associated with a lower CR rate (univariate analysis, P = 0.0342; CR 24% vs 53%) and were the only factor related to survival. These analyses warrant the further evaluation of the impact of cytogenetic abnormalities on the outcome of patients with advanced AML in order to improve the characterization according to duration of first CR and to WBC of distinct subgroups of patients with differing prognoses as a basis for stratification in future trials. Leukemia (2000) 14, 226-231.

Allogeneic stem cell transplantation in second rather than first complete remission in selected patients with good-risk acute myeloid leukemia

“…[17][18][19][20][21] A recurrent observation, also found in the present study, was that the duration of first CR strongly influenced second CR achievement and survival from reinduction. [17][18][19][20][21] In a large even if quite old study from Houston, duration of the initial remission positively correlated with a favorable karyotype including inv(16), t(8;21) and t(15;17) as well as with a lower incidence of antecedent hematologic disorders, high WBC and elevated creatinine or lactic acid dehydrogenase level. 17 In a more recent study from Vienna, favorable or normal cytogenetics was also associated with a better outcome after second CR.…”

“…The importance of diagnostic cytogenetics as prognostic factor for outcome in patients with AML led investigators to compare SCT and chemotherapy within each cytogenetic subgroup. Results show that SCT in first CR does not appear to benefit to relatively good-risk AML patients, as those with t (8,21), inv (16/t(16;16) or a normal karyotype (NN group). 8,9 The French AML Intergroup has recently reported the results of two large retrospective studies conducted in patients with t(8;21) and inv(16) AML, which both confirm this observation in patients with core binding factor (CBF) AML.…”

Impact of cytogenetics on the prognosis of adults with de novo AML in first relapse

“…We have previously reported that the proportion of patients with a favourable karyotype is high among patients with a duration of second CR of more than 2 years. 26 Kern et al 27 found that unfavourable cytogenetics were associated with a lower rate of second CR and was a poor prognostic factor with regard to survival after first relapse. In the above-mentioned studies, a validated prognostic classification of cytogenetics (like the classification according to the United Kingdom Medical Research Council (MRC)) was not yet available and clear data on OS and DFS according to the cytogenetic risk categories were not provided.…”

A comprehensive leukemia database: integration of cytogenetics, molecular genetics and microarray data with clinical information, cytomorphology and immunophenotyping

“…Because follow-up data from the AML-CG 20 study were included into the database we were able to confirm the prognostic relevance of specific cytogenetic or molecular genetic anomalies. 11,[21][22][23][24][25] The detection of new chromosomal aberration patterns is supported by a specific program providing frequency distributions of chromosome breakage points ordered by disease.…”

“…The integration of clinical and genetic data generates new scientific results; some examples in the field of leukemia research are provided in Refs 11,[21][22][23][24][25] Integration of clinical and scientific documentation requires significant efforts, but is feasible and provides better data quality and therefore faster research results. Before the integrated database was available, we lost up to 50% of cases when we combined several data sources automatically due to mismatch of patient demographic data and other inconsistencies.…”