Classifying Cytogenetics in Patients with Acute Myelogenous Leukemia in Complete Remission Undergoing Allogeneic Transplantation: A Center for International Blood and Marrow Transplant Research Study

Abstract

Cytogenetics play a major role in determining the prognosis of patients with AML. However, the existing cytogenetics classifications were developed on chemotherapy-treated patients and may not be optimal for patients undergoing allogeneic hematopoietic cell transplantation (HCT). We studied 821 adult patients reported to the CIBMTR who underwent HCT for AML in first or second CR between 1999 and 2004. We compared the ability of the 6 existing classifications to stratify patients by overall survival (OS). We then defined a new schema specifically applicable to HCT patients using this patient cohort. Under this CIBMTR schema, inv(16) is favorable, complex karyotype (4+ abnormalities) is adverse, and all other classified abnormalities are intermediate in predicting survival after HCT (5y OS 64%, 18%, and 50%, respectively, p=0.0001). This schema stratified patients into 3 groups with similar non-relapse mortality, but significantly different incidences of relapse, overall and leukemia-free survival. It applied to patients regardless of their disease status (CR1 or CR2), donor type (MRD or URD), or conditioning intensity (myeloablative or reduced intensity). This transplantation-specific classification could be adopted for prognostication purposes and to stratify patients with AML and karyotypic abnormalities entering HCT clinical trials.

Patient age, remission status and HCT-CI in a combined score are prognostic for patients with AML undergoing allogeneic hematopoietic cell transplantation in CR1 and CR2

“…We have addressed the latter issue by incorporating the year of transplant into the multivariable analysis, and this did not demonstrate any influence on the prognostic value of the developed scoring system. We must also note that in the present study, cytogenetic risk was classified according to the CIBMTR criteria, 11 which have not been confirmed in an independent validation. Repeat analysis of a larger, independent multicenter data set using the score we have developed would be required in validating the prognostic value of the score.…”

“…Conditioning intensity was myeloablative in 261 patients (67%) and reduced-intensity in 126 patients (33%). Concerning cytogenetic risk according to the CIBMTR criteria, 11 13 patients (3%) presented with favorable, 278 patients (72%) with intermediate and 34 patients (9%) with unfavorable risk cytogenetics. Among the intermediate cytogenetic risk patients, 154 demonstrated normal karyotype; however, a minority had data available on mutational status (FLT3-ITD and NPM1 mutations).…”

“…Cytogenetic risk at diagnosis was characterized as favorable, intermediate and unfavorable according to the previously described CIBMTR criteria. 11 The HCT-CI score 6 and Karnofsky performance status (KPS) were obtained retrospectively for each patient. This study was approved by the Cancer Registry Data Access Committee (CRDAC) and the Research Ethics Board of the University Health Network/Princess Margaret Cancer Centre.…”

Duration of first remission, hematopoietic cell transplantation-specific comorbidity index and patient age predict survival of patients with AML transplanted in second CR

“…The predictive role of cytogenetic risk for patients receiving an allograft as salvage therapy remains under debate. Studies by Armand et al, Fung et al, and Ferrant et al, [23][24][25] reported an increased RR and worse OS for patients transplanted with unfavorable cytogenetics. Our study demonstrated similar outcomes for patients transplanted in CR2 independent of their cytogenetic risk.…”

Therapy of Acute Myeloid Leukemia

“…Transplant of patients with AML in first CR: in patients who achieved CR, the role of allo-SCT is still under discussion. A variety of clinical studies have tried to evaluate the benefit of transplant in this situation, but most studies were non-randomized, non-controlled trials 3,5,6 . Only a few trials that were analyzed based on donor availability ('genetic' or 'biological' assignment) were useful as supporting evidence in the guideline recommendations, which were mainly based on cytogenetic risk factors.…”