Prognostic Factors in Patients Receiving An Allogeneic Stem Cell Transplantation for Relapsed AML. Results of the Prospective AML 295 and 01/99 Studies
Authors: Krauter Jürgen , Heil Gerhard , Hoelzer Dieter , Martin Hans , Ottmann Oliver G. , Finke Jürgen , Lübbert Michael , Heit Wolfgang , Fiedler Walter , Kanz Lothar , Schlimok Günter , Kirchner Hartmut , Raghavachar Aruna , Brugger Wolfram , Döhner Hartmut , Ganser Arnold 
Published: April 2020

Abstract
In the prospective multicenter AML 295 and 01/99 trials, we treated 825 adult patients with acute myeloid leukemia (AML) up to 60 years. 719 patients had de novo disease and 106 had a secondary AML. Median age was 46 years. Patients with t(15;17) were excluded. Induction course I consisted of standard dose araC, idarubicine and etoposide (IVA-I). Patients with good response to IVA-I (&lt;5% bone marrow blasts on day 15) continued with IVA-II on day 21 as double induction. Patients with bad response received an intensified second induction course with intermediate dose AraC (1g/m2, 8 doses) combined with mAMSA or fludarabine/idarubicine/G-CSF (FlAG-Ida). Double induction was followed by an early consolidation with intermediate dose AraC. Late consolidation was stratified according to risk factors (karyotype and response to IVA-I) and consisted of high dose AraC (3g/m2, 12 doses) + daunorubicine, autoPBSCT or an allogeneic stem cell transplantation. Overall complete remission (CR) rate was 75%. 278 patients relapsed after a median duration of first CR of 9 months. Of these 278 patients, 135 (48%) received an allogeneic stem cell transplantation (alloSCT) from related (n=65) or unrelated (n=70) donors. Median time from relapse to alloSCT was 3 months. 55% of the transplanted patients had achieved a second CR as best response to salvage therapy before alloSCT. Patients who received an alloSCT after relapse were younger (median 40 vs. 50 years) and had a longer duration of first CR (10 vs. 7.5 months) than those who did not. Patients with CBF-leukemias or normal karyotype were significantly more likely to receive an alloSCT after relapse than patients with other karyotypic aberrations. Median overall survival after alloSCT was 12 months and 5-year overall survival was 30%. Results did not differ between transplants from matched related or unrelated donors. In univariate and multivariate analysis, age above the median (HR 2.1, 95% CI 1.3 –3.2) and best response to salvage therapy (CR vs. no CR; HR 0.5, 95% CI 0.3 –0.9) were the only independent prognostic factors for overall survival after alloSCT. Patients aged below 46 years who achieved a CR as best response to salvage therapy had a 5-year overall survival after alloSCT of 53% (median not reached). All other patients had a 16% 5-year overall survival (median 7 months). There was no independent prognostic effect of WBC, platelets, peripheral blasts or extramedullary disease at initial diagnosis. Also, de novo vs. secondary AML, response to induction I, karyotype (CBF vs. normal vs. others), duration of CR1 (≥6 vs. &lt;6 months) and type of consolidation did not affect outcome after alloSCT in relapse. In conclusion, alloSCT from related or unrelated donors offers cure to selected patients with relapsed AML. Age and disease status after salvage therapy are critical prognostic factors for transplantation success. Strategies to increase the number of patients eligible for an alloSCT after relapse and age adapted transplantation protocols are required.