The prognostic value of cytogenetics is reinforced by the kind of induction/consolidation therapy in influencing the outcome of acute myeloid leukemia – analysis of 848 patients

Abstract

We studied the impact of cytogenetics and kind of induction/consolidation therapy on 848 adult acute myeloid leukemia (AML) patients (age 15-83). The patients received three types of induction/consolidation regimen: standard (daunorubicin and cytosine arabinoside (3/7); two cycles); intensive (idarubicin, cytosine arabinoside and etoposide (ICE), plus mitoxantrone and intermediate-dose Ara-C (NOVIA)); and low-dose (low-dose cytosine arabinoside). CR patients under 60 years of age, if an HLA-identical donor was available received allogeneic stem cell transplantation (allo-SCT); otherwise, as part of the program, they underwent autologous (auto)-SCT. CR rates significantly associated with 'favorable' (inv(16), t(8;21)), 'intermediate' ('no abnormality', abn(11q23), +8, del(7q)) and 'unfavorable' (del (5q), −7, abn(3)(q21q26), t(6;9), 'complex' (more than three unrelated cytogenetic abnormalities)) karyotypes (88% vs 65% vs 36%, respectively; P = 0.0001). These trends were confirmed in all age groups. On therapeutic grounds, intensive induction did not determine significant increases of CR rates in any of the considered groups, with respect to standard induction. Low-dose induction was associated with significantly lower CR rates. Considering disease-free survival (DFS), multivariate analysis of the factors examined (including karyotype grouping) showed that only age Ͼ60 years significantly affected outcome. However, in cases where intensive induction was adopted, 'favorable' karyotype was significantly related to longer DFS (P = 0.04). This was mainly due to the favorable outcome of t(8;21) patients treated with intensive induction. Patients receiving allo-SCT had significantly longer DFS (P = 0.005); in particular, allo-SCT significantly improved DFS in the 'favorable' and 'intermediate' groups (P = 0.04 and P = 0.048, respectively). In conclusion our study could provide some guidelines for AML therapy: (1) patients in the 'favorable' karyotype group seem to have a longer DFS when treated with an intensive induction/consolidation regimen, adopted before auto-SCT instead of standard induction; this underlines the importance of reinforcement of chemotherapy, not necessarily based on repeated high-dose AraC cycles. Allo-SCT, independently of induction/consolidation therapy, should be considered an alternative treatment; (2) patients in the 'intermediate' karyotype group should receive allo-SCT; (3) patients in the 'unfavorable' karyotype group should be treated using investigational chemotherapy, considering that even allo-SCT cannot provide a significantly longer DFS, but only a trend to a better prognosis. Leukemia (2001) 15, 903-909.

Improved outcome in relapsed and refractory myeloid malignancies for unrelated vs related donor allogeneic peripheral blood-derived hematopoietic cell transplantation

“…[2][3][4][5] Other currently recognized risk factors associated with a worse outcome include older age and development of acute or chronic GVHD. [6][7][8] The aim of this single-center retrospective study was to review the clinical characteristics and evaluate the potential predictors of RFS and OS in unrelated vs sibling donor HCT. Therefore, we analyzed the data of 92 consecutive adult patients with AML and myelodysplastic syndrome (MDS) undergoing their first peripheral blood-derived HCT from related or unrelated donors at the University of Freiburg Medical Center between 1996 and 2006 after treatment with a uniform preparative regimen consisting of high-dose oral BU and CY.…”

Inhibition of retinoic acid receptor signaling by Ski in acute myeloid leukemia

“…In our study, we were interested in the better molecular understanding of a clinical homogenous subgroup with a poor prognosis (AML with monosomy 7 or deletion 7q (À7/del7q)). [5][6][7][8] We analyzed samples from AML patients with À7/del7q, AML patients with normal karyotype (without FLT3 mutation) and normal bone marrow stem cells of healthy individuals, by gene expression profiling. Comparison of these three groups showed that the expression of SKI, a nuclear co-repressor of the HDAC complex, is highly upregulated in À7/del7q AML.…”

Impact of disease burden at time of allogeneic stem cell transplantation in adults with acute myeloid leukemia and myelodysplastic syndromes

“…8 For patients transplanted in CR1, cytogenetic pattern is also a significant predictor of outcome. [4][5][6][7][9][10][11][12] We were interested in evaluating these factors, as well as determining whether quantification of residual disease at the time of transplant was correlated with outcome. We were particularly interested in evaluating whether the percentage of residual bone marrow blasts, and/or detection of residual disease by cytogenetic analysis, affected the outcome after SCT.…”