Biomarkers, AlloHSCT Predict Post-AML Relapse Prognosis
NEW ORLEANS—Cytogenetic and molecular abnormalities evaluated at diagnosis of acute myeloid leukemia (AML) are prognostic for both the probability of first complete remission and patient survival. Now, results of a new study indicate that such factors, and treatment history, are prognostic of post-relapse prognosis, as well.
Allogeneic hematopoietic stem cell transplantation (AlloHSCT) after patients with AML suffer relapse, and CEBPAdm and CBF (core binding factor) rearrangement, are favorable prognostic factors, while internal tandem duplications of FLT3 (FLT3-ITD) represent an negative prognostic factor, according to authors of a study presented at the 55th American Society of Hematology Annual Meeting and Exposition.
“Cytogenetic and molecular abnormalities at initial diagnosis are the most powerful predictive factors in AML,” reported lead author Richard Schlenk, MD, of the University Hospital of Ulm, in Ulm, Germany, and coauthors. “Patients with relapsed AML have an overall probability of less than 50% to achieve a CR2 (second complete remission) and CR3 after intensive salvage chemotherapy; the only exceptions are AML with CEBPAdm and CBF-AML. AlloHSCT either as direct treatment of relapse or as salvage therapy after failure of intensive chemotherapy may overcome chemo-resistance.”
Data for a total of 3,218 patients were analyzed at a median follow-up after relapse of 4.3 years. Survival was significantly higher among patients who underwent alloHSCT after relapse than among those who did not (odds ratio [OR], 5.50; P < 0.001), Dr. Schlenk reported.
In treated patients, the overall CR rate was 38%, Dr. Schlenk said. Shorter first CR duration and older age were associated with inferior outcomes, he noted.
“Allogenic HSCT either as a direct treatment of relapse or as salvage therapy after failure of intensive chemotherapy may overcome chemoresistance,” Dr. Schlenk said.
Multivariate analysis including alloHSCT revealed that in addition to alloHSCT performed after relapse, favorable factors included biallelic CEBPA mutation (HR [hazard ratio], 0.54; P = 0.0039) and CBF-AML (HR, 0.55; P < 0.0001). CBF-AML is cytogenetically determined as the presence of t(8;21)(q22;q22) or inv(16)(p13q22)/t(16;16)(p13;q22).
Unfavorable factors included high-risk cytogenetics (HR, 1.23; P = 0.044) and FLT3-ITD (HR, 1.31; P = 0.0053), Dr. Schlenk reported.
Dr. Schlenk and his coauthors disclosed funding from Celgene, Pfizer, Amgen, Novartis, and Ambit.