A Novel Risk Score Predicts the Likelihood of a Complete Remission After Intensive Induction Therapy in Older AML Patients.
Authors: Krug Utz O. , Heinecke Achim , Koschmieder Anja , Stelljes Matthias , Sauerland Maria Cristina , Berdel Wolfgang E , Woermann Bernhard J , Hiddemann Wolfgang , Buchner Thomas , Müller-Tidow Carsten 
Published: October 2019

Abstract
Abstract 327

Introduction:
Older patients (≥ 60 years) with acute myeloid leukemia (AML) display a dismal prognosis with only half of the patients reaching a complete remission after intensive induction therapy. The decision whether or not to use intensive chemotherapy is often difficult given the limited number of known markers that might predict the chance to achieve a complete remission. The aim of this study was to establish a risk score for therapy-failure based on clinical variables for older but medically fit AML patients.

Patients and Methods:
1379 patients ≥ 60 years of age with AML evaluable for an induction result after treatment with an intensive induction regimen (randomized standard-dose cytarabine containing TAD or high-dose cytarabine (1g/sqm × 6) containing HAM, with a second induction course HAM in case of blast persistence after the first course) within the AMLCG1999 study of the German AML Co-operative Group were evaluated. The following parameters were evaluated for risk prediction in an exploratory analysis: Age, sex, de novo versus secondary leukemia, performance status, body mass index, body temperature, presence of extramedullary manifestations, spleen size, presence of lymph node enlargement, hemoglobin, peripheral blood leukocytes, platelets, blast percentage in peripheral blood and bone marrow, total protein in serum, alanine aminotransferase (ALT), alkaline phosphatase (AP), bilirubin, lactate dehydrogenase (LDH), FAB classification, prothrombin time (PT) and fibrinogen. Since cytogenetics and molecular markers are often not available at the time of decision making, these data were not included.

Results:
Within this cohort of patients, 744 (54 %) achieved a complete remission. Among the analyzed parameters, age, de novo versus secondary leukaemia, body mass index, body temperature, hemoglobin, peripheral blood leukocytes, platelets, bone marrow and peripheral blood blasts, ALT, AP, LDH, PT and fibrinogen were significantly associated with a CR (p<0.05) in a univariate log rank analysis. In a multivariate logistic regression model, the following parameters retained its significance: age (60 – 63 years, 64 – 67 years, 68 – 72 years, ≥ 73 years) de novo versus secondary leukemia, body temperature (≤ 36°C, > 36°C – 38°C, > 38°C), hemoglobin (≤ 10.3 g/dl versus > 10.3 g/dl), platelets (≤ 28,000, > 28,000 - 53000, > 53,000 – 103,000, > 103,000 per μl), AP (≤ 89 U/l versus > 89 U/l), PT (≤ 75 %, > 75 – 87 %, > 87 – 98 %, > 98 %) and fibrinogen (≤ 150 mg/dl versus > 150 mg/dl). Based on these parameters, the predicted remission rates were: minimum, 18.3 %; 1st quartile, 43.9 %; median, 54.4 %;3rd quartile, 64.3 %; maximum: 88.1 %. The observed remission rates were: 1st quarter, 35.7 %; 2nd quarter, 50.3 %; 3rd quarter, 60.2 %; 4th quarter, 69.8 %.

Conclusions:
Taken together, this risk prediction score based on pre-treatment values predicted the remission probability in patients ≥ 60 years of age with AML receiving an intensive induction therapy. This score may be useful for the determination of the therapy strategy in elderly patients with AML.

Disclosures:
No relevant conflicts of interest to declare.