Prognosis of patients with core binding factor acute myeloid leukemia after first relapse

Abstract

ABSTRACTfirst relapse after being treated with chemotherapy alone during CR1. Methods PatientsAdults with AML who had achieved CR1 were retrospectively registered in a nationwide AML database, which formed the basis of this study. 6,9 This database included patients who were between 16 and 70 years of age, were diagnosed with AML between 1999 and 2006 according to the World Health Organization classification, and had achieved CR with one or two courses of chemotherapy. Seventy institutions contributed patients to the database. In the original database, information was collected on patient-related factors (e.g., age, sex), diseaserelated factors [e.g., cytogenetics, white blood cell (WBC) count at diagnosis], and clinical outcome including the date of relapse and achievement of CR2. For patients who underwent allogeneic HCT after relapse, complementary information on HCT (e.g., interval from relapse to HCT, disease status at the time of HCT, conditioning regimen, and donor source) was also collected. To perform this current study, supplementary information was collected for CBF-AML patients who had their first hematologic relapse. Additional data collected concerned cytogenetics and WBC count at first relapse, chemotherapy regimen adopted after the first relapse, and response to the initial treatment after the first relapse. Chromosome analysis was performed on metaphases from samples of bone marrow using standard banding techniques. Karyotypes were determined according to the International System for Human Cytogenetic Nomenclature. The cytogenetic data at relapse were centrally reviewed by a doctor who specialized in chromosome analysis, and classified into 'same cytogenetics' or 'different cytogenetics' from those at diagnosis. We categorized the "different cytogenetics" into three groups: decrease in cytogenetic abnormalities, increase in cytogenetic abnormalities, and unrelated change. A decrease or increase in cytogenetic abnormalities was defined as different chromosomal karyotypes harboring the original CBF-associated abnormality. Unrelated change was defined as a chromosomal karyotype that lost the original CBF-associated abnormality. The increase in cytogenetic abnormalities was further subdivided into two groups: numerical changes [e.g., 46,XY,inv(16)(p13;q22) → 47,XY,inv(16)(p13q22),+22] and structural changes [e.g., 46,XX,t(8;21)(q22;q22) → 46,XX,t(8;21)(q22;q22), t(9;10)(q34;q11)]. This study was approved by the Institutional Review Board at the National Cancer Centre Hospital. Statistical analysisData were retrospectively reviewed and analyzed as of March 2012. Distributions of patients' characteristics between groups were compared using the chi-square test for categorical variables and the Wilcoxon rank-sum test for continuous variables. A Kaplan-Meier survival analysis was performed to estimate the probabilities of overall survival, which was defined as the time from the first relapse to death or the last visit. Differences in overall survival between groups were compared by means of the log-r...

Clonal evolution detected with conventional cytogenetic analysis is a potent prognostic factor in adult patients with relapsed AML

“…Although t(8;21) and a complex karyotype were extracted as independent predisposing factors, the great discrepancy in ACA acquisition incidences in core-binding factor AML was noteworthy. The difference in prognosis after the first relapse between t(8;21) and inv16 was described in the study by Kurosawa et al, 22 and their finding may be Overall survival in relapsed AML patients with ACA and after the first relapse in relapsed AML patients with ACA acquisition according to the treatment strategy, allogeneic stem cell transplantation (allo-SCT), or chemotherapy alone explained with the higher incidence of ACA acquisition in t (8;21) patients in our current study.…”

“…Although t(8;21) and a complex karyotype were extracted as independent predisposing factors, the great discrepancy in ACA acquisition incidences in core‐binding factor AML was noteworthy. The difference in prognosis after the first relapse between t(8;21) and inv16 was described in the study by Kurosawa et al, and their finding may be explained with the higher incidence of ACA acquisition in t(8;21) patients in our current study.…”

Identification of molecular and cytogenetic risk factors for unfavorable core-binding factor-positive adult AML with post-remission treatment outcome analysis including transplantation

“…26 In a recent report, 3-year OS after allo-HSCT in second CR was 48%. 27 Although this OS rate is higher than the 30% of non-CBF-AML in second CR, 5 frontline auto-HSCT or allo-HSCT should be reconsidered for CBF-AML with adverse-risk factors and when the CBF-MRD qPCR is not properly reduced to an acceptable level after treatments. Given this point of view, our data can be a reference for future prospective studies that implicate frontline HSCT for CBF-AML.…”

Prognostic significance of recurring chromosomal abnormalities in transplanted patients with acute myeloid leukemia

“…Indeed, a fundamental premise of the risk stratification schemes employed in the past two decades has been that patients with specifically designated higher risk recurring cytogenetic abnormalities, namely those patients harboring a complex [9,10] or monosomal [11][12][13] karyotype for example, are referred to transplant at first remission. Conversely, patients with better prognosis karyotypic lesions such as core binding factor (CBF), are typically consolidated with chemotherapy [14,15]. Whereas the prognostic significance of these commonly occurring cytogenetic aberrations is clearly established, the clinical impact of the full gamut of less commonly recurring chromosomal changes was uncovered by the extensive analyses undertaken by the United Kingdom Medical Research Council (UKMRC) which diligently delineated the specific prognoses effected by the full spectrum of cytogenetic aberrations seen in AML [16].…”