Article

Prognostic value of monosomal karyotype in comparison to complex aberrant karyotype in acute myeloid leukemia: a study on 824 cases with aberrant karyotype

MLL Munich Leukemia Laboratory, Max-Lebsche-Platz 31, Munich, Germany.
Blood (Impact Factor: 9.78). 12/2011; 119(9):2122-5. DOI: 10.1182/blood-2011-10-385781
Source: PubMed

ABSTRACT In acute myeloid leukemia (AML) the subset with complex karyotype (CK) is traditionally regarded as the worst prognostic group. However, ≥ 3, ≥ 4, or ≥ 5 abnormalities have been variably used for its definition. Recently, monosomal karyotype (MSK) was suggested to indicate an even inferior outcome. We tested which definition fits best to identify the most unfavorable subgroup. After excluding patients with t(15;17)/PML-RARA, t(8;21)/RUNX1-RUNX1T1, inv (16)/t(16;16)/CBFB-MYH11, and normal karyotype, 824 patients with AML with cytogenetic abnormalities were analyzed. Patients with MSK or CK defined as ≥ 3, ≥ 4, or ≥ 5 abnormalities showed an inferior overall survival compared with the respective remaining patients not fulfilling these criteria (for all, P < .001). Hazard ratios were 1.93, 1.68, 1.94, and 1.92. CK ≥ 4 as a single parameter identified the largest proportion of patients with very poor risk. However, combining CK ≥ 4 and MSK detected an even larger number of patients with very unfavorable outcome (261 of 824; 31.7%).

1 Bookmark
 · 
172 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND The karyotype is a predictor of outcomes in adults with acute lymphoblastic leukemia (ALL). The unfavorable prognostic significance of complex karyotype (CK) has been reported, whereas the prognostic relevance of monosomal karyotype (MK) has not been consistently evaluated. We aimed to assess the prognostic value of CK and MK in adults with ALL treated with risk-adapted protocols of the Spanish PETHEMA Group.METHODS The karyotypes of 881 adult ALL patients treated according to the protocols of the PETHEMA Group between 1993 and 2012 were centrally reviewed. CK and MK were assessed according to Moorman's criteria, and Breem's criteria, respectively. Specific analyses according to the risk groups and to the presence of t(9:22) were performed.RESULTSOf 364 evaluable patients 33 (9.2%) had CK, and 68 of 535 evaluable patients (12.8%) had MK. Complete remission rate, remission duration, and overall survival were not significantly different according to the presence of CK or MK in the whole series, according to the B or T lineage, in the high-risk group, or in patients with t(9;22), regardless of imatinib treatment, and in patients who received chemotherapy alone or chemotherapy followed by stem cell transplantationCONCLUSIONS Our study shows that CK and MK were not associated with a worse prognosis in adult patients with ALL treated with risk-adapted or subtype-oriented protocols. In patients with Ph+ ALL, MK did not have an impact on prognosis irrespective of imatinib treatment. Cancer. © 0000 American Cancer Society Cancer 2014. © 2014 American Cancer Society.
    Cancer 08/2014; 120(24). DOI:10.1002/cncr.28950 · 5.20 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Purpose: Recurrent gene mutations, chromosomal translocations and acquired genomic copy number aberrations (aCNA) have been variously associated with AML patient outcome. However, knowledge of the co-occurrence of such lesions and the relative influence of different types of genomic alterations on clinical outcomes in AML is still evolving. Experimental Design: We performed SNP 6.0 array-based genomic profiling of aCNA/cnLOH along with sequence analysis of 13 commonly mutated genes on purified leukemic blast DNA from 156 prospectively enrolled non-FAB-M3 AML patients across the clinical spectrum of de novo, secondary, and therapy-related AML. Results: TP53 and RUNX1 mutations are strongly associated with the presence of SNP-A-based aCNA/cnLOH, while FLT3 and NPM1 mutations are strongly associated with the absence of aCNA/cnLOH. The presence of mutations in RUNX1, ASXL1 and TP53, elevated SNP-A-based genomic complexity, and specific recurrent aCNAs predicted failure to achieve a complete response to induction chemotherapy. The presence of ≥1 aCNA/cnLOH and higher thresholds predicted for poor long-term survival irrespective of TP53 status, and the presence of ≥1 aCNA/cnLOH added negative prognostic information to knowledge of mutations in TET2, IDH1, NPM1, DNMT3A and RUNX1. Results of multivariate analyses support a dominant role for TP53 mutations and a role for elevated genomic complexity as predictors of short survival in AML. Conclusions: Integrated genomic profiling of a clinically relevant adult AML cohort identified genomic aberrations most associated with SNP-A-based genomic complexity, resistance to intensive induction therapies and shortened overall survival. Identifying SNP-A-based lesions adds prognostic value to the status of several recurrently mutated genes. Copyright © 2015, American Association for Cancer Research.
    Clinical Cancer Research 02/2015; DOI:10.1158/1078-0432.CCR-14-0921 · 8.19 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Genetic aberrations have become a dominant factor in the stratification of myeloid malignancies. Cytogenetic and a few mutation studies are the backbone of risk assessment models of myeloid malignancies which are a major consideration in clinical decisions, especially patient assignment for allogeneic stem cell transplantation. Progress in our understanding of the genetic basis of the pathogenesis of myeloid malignancies and the growing capabilities of mass sequencing may add new roles for the clinical usage of genetic data. A few recently identified mutations recognized to be associated with specific diseases or clinical scenarios may soon become part of the diagnostic criteria of such conditions. Mutational studies may also advance our capabilities for a more efficient patient selection process, assigning the most effective therapy at the best timing for each patient. The clinical utility of genetic data is anticipated to advance further with the adoption of deep sequencing and next-generation sequencing techniques. We herein suggest some future potential applications of sequential genetic data to identify pending deteriorations at time points which are the best for aggressive interventions such as allogeneic stem cell transplantation. Genetics is moving from being mostly a prognostic factor to becoming a multitasking decision support tool for hematologists. Physicians must pay attention to advances in molecular hematology as it will soon be accessible and influential for most of our patients.
    10/2014; 5(4):e0025. DOI:10.5041/RMMJ.10159